Rett SyndromePhase 2NCT01777542

Treatment of Rett Syndrome With Recombinant Human IGF-1

A Phase 2 study testing Recombinant Human Insulin Growth Factor 1 (rhIGF-1) in people with Rett Syndrome, run by Boston Children's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 2 to 10 years, women only
Conditions the study is for: Rett Syndrome
What is being tested?: Recombinant Human Insulin Growth Factor 1 (rhIGF-1)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Jan 2013to Nov 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 10 years
Women only
No healthy volunteers
Child

Who may be able to join

Diagnosis of "classic" (or "typical") Rett Syndrome
Genetic documentation of MECP2 mutation
Subject must be post-regression (Hagberg Stage 2)
Subject and caregiver's primary language must be English
Subject must reside in North America (US and Canada)
Caregiver must have internet access and be able to complete questionnaires online and communicate via email
Subject is stable on current medications for at least 4 weeks
Subject's regimen of non-pharmacological interventions (physical therapy, speech therapy, etc.) is stable for at least 90 days

Who cannot join

Severe scoliosis (curvature >40 degrees)
Bone-age greater than 11 years
Cardiomegaly (enlarged heart)
Tanner stage 2 or higher breast development
Allergy to IGF-1
Prior use of IGF-1, growth hormone, or sex steroids

Trial locations and contacts

1 site in 1 country.

United States1 site

Boston Children's Hospital
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With Recombinant Human IGF-1(Mecasermin [rDNA] Injection)

Investigators are recruiting children for a clinical trial using the medication recombinant human IGF-1 (a.k.a. mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). While IGF-1 is approved by the Food \& Drug Administration (FDA) for certain use in children, it is considered an investigational drug in this trial because it has not previously been used to treat RTT. Information from this study will help determine if IGF-1 effectively treats RTT but will not necessarily lead to FDA approval of IGF-1 as a treatment for RTT.

Read the detailed description

Enrolled subjects will complete five study periods: screening, two 20-week long treatment periods, a 28-week break between treatment periods ("washout"), and a follow-up phone call 4 weeks after all treatment ends. Subjects will be chosen at random to receive either IGF-1 or placebo during the first treatment period and then switch to the alternate medication for the second treatment period. Therefore, by completion of the trial, all subjects will have received treatment with IGF-1 for 20 weeks. The study will be double-blinded; meaning, neither subjects' families nor study investigators will know who is receiving IGF-1 or placebo at any time. Treatment must be administered by the caregiver twice daily through subcutaneous (just underneath the skin) injections. Caregivers will be trained by research nurses in how to administer the medication. Participation in this study will last approximately eighteen months.

Throughout the course of the trial, investigators will collect information to assess the effects of IGF-1 and monitor for safety. Families must attend study visits at Boston Children's Hospital a total of seven times (including the screening visit) over the course of 18 months. These visits cannot be completed at any other hospital. Parents will fill out questionnaires and undergo a structured interview reporting on their child's health, behavior, and mood. Subjects will undergo clinical and physical examinations by a study doctor. Non-invasive devices and cameras will also be used to monitor things like breathing, hand movements, heart rate, and body temperature. Blood and urine will be collected for routine laboratory tests to monitor for safety. Investigators will also monitor safety by asking parents to complete a medication diary and side effect reporting form on a regular basis. Between trips to Boston Children's Hospital, parents will complete a set of online questionnaires and undergo a structured interview over the phone.

The cost of travel and lodging during research-related visits to and from the hospital will not be covered by the study. If a condition or illness is identified during the trial (and is determined to be unrelated to study treatments), referrals to outside medical care will be made. Study medications and all research-related materials and services will be provided at no cost to participants. Parking vouchers will be provided for all study-related hospital visits.

The study is investigating 5 potential effects:

IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure this, investigators will evaluate subjects every 5 weeks throughout each treatment period with behavioral and psychological assessments. All of the tests used during these evaluations are non-invasive. Investigators will ask parents what their impressions are about their child's behavior and day-to-day activities through a structured parental interview and various questionnaires.
Investigators will examine subjects' brain function through use of a brain- monitoring device known as electroencephalography (EEG). The EEG measurements will be taken while investigators present subjects with exercises to stimulate their vision and hearing. EEG is a non-invasive way of recording the electrical activity of a subject's brain by applying a net of monitors (electrodes) to their scalp. Through this method investigators gain insight into how brain processes visual and auditory stimulus.
As one of the features of RTT is unstable vital signs, investigators are trying to determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing patterns. To measure this, investigators will ask subjects to wear a non-invasive device that includes three electrocardiogram connectors and two stretchy bands that wrap around her chest and abdomen to measure heart rate and respiratory patterns.
The safety of IGF-1 in children with RTT is very important. Investigators will ask parents to complete a medication diary and side effect reporting form on a regular basis. In addition, laboratory tests will be performed every 10 weeks throughout each treatment period to evaluate the safety of IGF-1. These will be blood tests similar to those provided in typical clinical care. Subjects will undergo regular non-invasive comprehensive physical and neurological examinations, tonsil evaluation, electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray, ophthalmological exam, and measurements of height, weight and head circumference.
Children with RTT often experience unintended, stereotyped hand movements. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures subjects' movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects the presentation of stereotyped hand movements. As such, investigators will ask subjects to wear the Qsensor® during study visits every 10 weeks throughout each treatment period and occasionally at home.

Conditions: Rett Syndrome
Being tested: Recombinant Human Insulin Growth Factor 1 (rhIGF-1), Placebo
Keywords: Rett syndrome, RTT, IGF-1, autism spectrum disorder
Medical subject headings: Rett Syndrome, Autism Spectrum Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Recombinant Human Insulin Growth Factor 1 (rhIGF-1)Drug
Also called mecasermin [rDNA] injection, Increlex
Subjects will receive twice daily subcutaneous injections of IGF-1.
PlaceboDrug
Also called saline
Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).

Study groups in NCT01777542
Study group	Role	What they receive
Treatment Period 1	Active comparator	One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) , and the other half of subjects will be randomly assigned to receive placebo. Receives: Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1); Drug: Placebo
Treatment Period 2	Placebo comparator	Subjects that initially received Recombinant Human Insulin Growth Factor 1 (rhIGF-1) will now receive placebo, and subjects that initially received placebo will now receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1). Receives: Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1); Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale
The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true."
The total sum of items in each subscale is reported.
For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale
The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem.
The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Clinical Global Impression - Severity (CGI-S)
This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired.
The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired.
The possible range for reported scores is 1-7.
Measured: Every 10 weeks during each of the two 20-week treatment periods
Clinical Global Impression - Improvement (CGI-I)
Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.
The possible range for reported scores is 1-7.
Measured: Every 10 weeks during each of the two 20-week treatment periods
Parental Global Impression - Severity (PGI-S)
The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit.
The scores that correspond to each possible grouping are as follows:
1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired.
The possible range for reported scores is 1-7.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Parental Global Impression - Improvement (PGI-I)
As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.
The possible range for reported scores is 1-7.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).
The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).
The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).
The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Kerr Clinical Severity Scale
The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations.
The possible range of scores is 0-48. The higher the score, the more severe the symptoms.
Measured: At the start and end of each 20-week treatment period

Secondary outcomes (7)

Rett Syndrome Behavior Questionnaire (RSBQ)
The RSBQ is a parent-completed measure of abnormal behaviors typically observed in individuals with RTT. Each item, grouped into eight subscales, is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true."
The total sum of each subscale is reported. The higher the score, the more severe the symptoms of that subscale in the participant.
The range for each subscale is as follows:
General Mood: 0-16 Body rocking and expressionless face: 0-14 Hand behaviors: 0-12 Breathing Problems: 0-10 Repetitive Face Movements: 0-8 Night-time behaviors: 0-6 Walking Standing: 0-4
The fear/anxiety subscale was used as a primary outcome measure in this study and results can be found in that section.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Anxiety, Depression, and Mood Scale (ADAMS)
Remaining subscales of the ADAMS that are not primary outcome measures include: Manic/hyperactive, Depressed mood, General anxiety, Obsessive/compulsive behavior.
The range for each subscale is as follows:
Manic/Hyperactive Behavior: 0-15 Depressed Mood: 0-21 General Anxiety: 0-21 Obsessive/Compulsive Behavior: 0-9
The higher the score for each subscale, the more problematic the behavior.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Mullen Scales of Early Learning (MSEL)
The MSEL is a standardized developmental test for children ages 3 to 68 months consisting of five subscales: gross motor, fine motor, visual reception, expressive language, and receptive language.
The raw score is reported for each subscale domain. The potential score ranges are as follows:
Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. The gross motor subscale was not included in this population.
A higher raw score indicates more advanced abilities in that section.
Measured: At the start and end of each 20-week treatment period
Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
The VABS-II is a survey designed to assess personal and social functioning. Within each domain (Communication, Daily Living Skills, Socialization, and Motor Skills), items can given a score of "2" if the participant successfully performs the activity usually; a "1" if the participant successfully performs the activity sometimes, or needs reminders; a "0" if the participant never performs the activity, and a "DK" if the parent/caregiver is unsure of the participant's ability for an item.
The raw scores in each sub-domain are reported and the ranges for these are as follows: [Communication Domain], Receptive Language=0-40, Expressive Language=0-108, Written Language=0-50; [Daily Living Skills Domain], Personal=0-82, Domestic=0-48, Community=0-88; [Socialization Domain], Interpersonal Relationships=0-76, Play and Leisure Time=0-62, Coping Skills=0-60; [Motor Skills Domain]: Gross Motor Skills=0-80, Fine Motor Skills=0-72.
A higher score indicates more advanced abilities.
Measured: At the start and end of each 20-week treatment period
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)
The CSBS-DP was designed to measure early communication and symbolic skills in infants and young children (that is, functional communication skills of 6 month to 2 year olds). The CSBS-DP measures skills from three composites: (a) Social (emotion, eye gaze, and communication); (b) Speech (sounds and words); and (c) Symbolic (understanding and object use) and asks about developmental milestones. The data reported are the composite scores for these three categories.
The possible scores for the three composite categories are as follows:
Social Composite = 0-48; Speech Composite = 0-40; Symbolic Composite = 0-51.
A higher score indicates more advanced abilities in that area.
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Aberrant Behavior Checklist - Community Edition (ABC-C)
The ABC-C is a global behavior checklist implemented for the measurement of drug and other treatment effects in populations with intellectual disability. Behavior based on 58 items that describe various behavioral problems.
Each item is rated on the parents perceived severity of the behavior. The answer options for each item are:
0 = Not a problem
1. = Problem but slight in degree
2. = Moderately serious problem
3. = Severe in degree
The measure is broken down into the following subscales with individual ranges as follows:
Subscale I (Irritability): 15 items, score range = 0-45 Subscale II (Lethargy): 16 items, score range = 0-48 Subscale III (Stereotypy): 7 items, score range = 0-21 Subscale IV (Hyperactivity): 16 items, score range = 0-48 Subscale V (Inappropriate Speech) was not included in the breakdown because it was not applicable (no participants in the study had verbal language).
Measured: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Quantitative Measures of Respiration: Apnea Index
Respiratory data was collected using non-invasive respiratory inductance plethysmography from a BioCapture® recording device. BioCapture® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and the 3 lead ECG signals we plan to use for monitoring cardiac safety throughout the study. Each transducer is placed on the patient independently to provide a customized fit that yields the highest signal quality for each patient irrespective of body shape and proportion. The transducer signals captured by the BioCapture® are transmitted wirelessly to a laptop computer where all signals are displayed in real-time.
The apnea index is given as apneas/hour. Data on apneas greater than or equal to 10 seconds are displayed below. The higher the frequency of apnea, the more severe the breathing abnormality.
Measured: Every 10 weeks during each of the two 20-week treatment periods

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2013Nov 2016

First posted29 Jan 2013 (estimated)
Study startJan 2013
Primary completionJul 2016
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (57)Papers the sponsor has linked to this study.
Other trials for Rett SyndromeStudies of the same condition, open and under way.
More trials run by Boston Children's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01777542
Sponsor's protocol ID: IRB-P00005610
Status last verified: Mar 2018
First submitted: 23 Jan 2013
Last updated: 26 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.
PubMed 24623853
Schultz RJ, Glaze DG, Motil KJ, Armstrong DD, del Junco DJ, Hubbard CR, Percy AK. The pattern of growth failure in Rett syndrome. Am J Dis Child. 1993 Jun;147(6):633-7. doi: 10.1001/archpedi.1993.02160300039018.
PubMed 8506830
Williamson SL, Christodoulou J. Rett syndrome: new clinical and molecular insights. Eur J Hum Genet. 2006 Aug;14(8):896-903. doi: 10.1038/sj.ejhg.5201580.
PubMed 16865103
Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Silvestri JM, Ramirez JM. Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr Res. 2006 Oct;60(4):443-9. doi: 10.1203/01.pdr.0000238302.84552.d0. Epub 2006 Aug 28.
PubMed 16940240
Percy AK. Clinical trials and treatment prospects. Ment Retard Dev Disabil Res Rev. 2002;8(2):106-11. doi: 10.1002/mrdd.10022.
PubMed 12112736
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. doi: 10.1038/13810.
PubMed 10508514
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998 May 28;393(6683):386-9. doi: 10.1038/30764.
PubMed 9620804
Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet. 2002 Jan 15;11(2):115-24. doi: 10.1093/hmg/11.2.115.
PubMed 11809720
Cohen DR, Matarazzo V, Palmer AM, Tu Y, Jeon OH, Pevsner J, Ronnett GV. Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci. 2003 Apr;22(4):417-29. doi: 10.1016/s1044-7431(03)00026-5.
PubMed 12727440
Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM. Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry. 2006 Mar 1;59(5):468-76. doi: 10.1016/j.biopsych.2005.07.025. Epub 2005 Sep 30.
PubMed 16199017
Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001 Mar;27(3):322-6. doi: 10.1038/85899.
PubMed 11242117
Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron. 2002 Jul 18;35(2):243-54. doi: 10.1016/s0896-6273(02)00768-7.
PubMed 12160743
Giacometti E, Luikenhuis S, Beard C, Jaenisch R. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1931-6. doi: 10.1073/pnas.0610593104. Epub 2007 Jan 31.
PubMed 17267601
Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron. 2007 Oct 4;56(1):58-65. doi: 10.1016/j.neuron.2007.08.018.
PubMed 17920015
Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12560-5. doi: 10.1073/pnas.0506071102. Epub 2005 Aug 22.
PubMed 16116096

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With Recombinant Human IGF-1(Mecasermin [rDNA] Injection)
ClinicalTrials.gov ID: NCT01777542
Acronym / sponsor ID: IRB-P00005610
Conditions: Rett Syndrome
Keywords: Rett syndrome, RTT, IGF-1, autism spectrum disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Boston Children's HospitalUniversity, hospital or other
Collaborators: International Rett Syndrome Foundation
Study start: Jan 2013
Primary completion: Jul 2016 (actual)
Study completion: Nov 2016 (actual)
First posted: 29 Jan 2013 (estimated)
Results: Posted 26 Mar 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study is investigating 5 potential effects:

IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure this, investigators will evaluate subjects every 5 weeks throughout each treatment period with behavioral and psychological assessments. All of the tests used during these evaluations are non-invasive. Investigators will ask parents what their impressions are about their child's behavior and day-to-day activities through a structured parental interview and various questionnaires.
Investigators will examine subjects' brain function through use of a brain- monitoring device known as electroencephalography (EEG). The EEG measurements will be taken while investigators present subjects with exercises to stimulate their vision and hearing. EEG is a non-invasive way of recording the electrical activity of a subject's brain by applying a net of monitors (electrodes) to their scalp. Through this method investigators gain insight into how brain processes visual and auditory stimulus.
As one of the features of RTT is unstable vital signs, investigators are trying to determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing patterns. To measure this, investigators will ask subjects to wear a non-invasive device that includes three electrocardiogram connectors and two stretchy bands that wrap around her chest and abdomen to measure heart rate and respiratory patterns.
The safety of IGF-1 in children with RTT is very important. Investigators will ask parents to complete a medication diary and side effect reporting form on a regular basis. In addition, laboratory tests will be performed every 10 weeks throughout each treatment period to evaluate the safety of IGF-1. These will be blood tests similar to those provided in typical clinical care. Subjects will undergo regular non-invasive comprehensive physical and neurological examinations, tonsil evaluation, electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray, ophthalmological exam, and measurements of height, weight and head circumference.
Children with RTT often experience unintended, stereotyped hand movements. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures subjects' movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects the presentation of stereotyped hand movements. As such, investigators will ask subjects to wear the Qsensor® during study visits every 10 weeks throughout each treatment period and occasionally at home.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Treatment Period 1	Active comparator	Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1), Drug: PlaceboOne half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) , and the other half of subjects will be randomly assigned to receive placebo.
Treatment Period 2	Placebo comparator	Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1), Drug: PlaceboSubjects that initially received Recombinant Human Insulin Growth Factor 1 (rhIGF-1) will now receive placebo, and subjects that initially received placebo will now receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1).

Who may qualify

Ages: 2 to 10 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

Diagnosis of "classic" (or "typical") Rett Syndrome
Genetic documentation of MECP2 mutation
Subject must be post-regression (Hagberg Stage 2)
Subject and caregiver's primary language must be English
Subject must reside in North America (US and Canada)

Key exclusion criteria (6 listed)

Severe scoliosis (curvature >40 degrees)
Bone-age greater than 11 years
Cardiomegaly (enlarged heart)
Tanner stage 2 or higher breast development
Allergy to IGF-1

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Recombinant Human Insulin Growth Factor 1 (rhIGF-1)Also: mecasermin [rDNA] injection, IncrelexSubjects will receive twice daily subcutaneous injections of IGF-1.	Drug	Treatment Period 1, Treatment Period 2
PlaceboAlso: salineSubjects will receive twice daily subcutaneous injections of a saline solution (placebo).	Drug	Treatment Period 1, Treatment Period 2

Primary outcome

Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of items in each subscale is reported. For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors.
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem. The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior.
Clinical Global Impression - Severity (CGI-S)
Time frame: Every 10 weeks during each of the two 20-week treatment periods
This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.
Clinical Global Impression - Improvement (CGI-I)
Time frame: Every 10 weeks during each of the two 20-week treatment periods
Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.
Parental Global Impression - Severity (PGI-S)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.
Parental Global Impression - Improvement (PGI-I)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.
Kerr Clinical Severity Scale
Time frame: At the start and end of each 20-week treatment period
The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations. The possible range of scores is 0-48. The higher the score, the more severe the symptoms.

7 secondary outcomes

Rett Syndrome Behavior Questionnaire (RSBQ)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Anxiety, Depression, and Mood Scale (ADAMS)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Mullen Scales of Early Learning (MSEL)
Time frame: At the start and end of each 20-week treatment period
Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
Time frame: At the start and end of each 20-week treatment period
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Aberrant Behavior Checklist - Community Edition (ABC-C)
Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
Quantitative Measures of Respiration: Apnea Index
Time frame: Every 10 weeks during each of the two 20-week treatment periods

Results and safety

Results posted to the registry on 26 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo First, Then rhIGF-1	15	15
rhIGF-1 First, Then Placebo	15	15

Primary outcome: Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale

Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends. Median (Inter-Quartile Range). Unit: units on a scale

Measure	Placebo First, Then rhIGF-1 n = 15	rhIGF-1 First, Then Placebo n = 15
Visit 1 - First Intervention	4.00 (3.00 to 6.00)	5.00 (2.00 to 6.00)
Visit 2 - First Intervention	5.00 (3.00 to 6.00)	3.00 (2.00 to 5.00)
Visit 3 - First Intervention	4.00 (3.00 to 5.00)	3.00 (2.00 to 5.00)
Visit 4 - First Intervention	4.00 (2.00 to 5.00)	3.00 (1.00 to 6.00)
Visit 5 - First Intervention	3.00 (2.00 to 5.00)	3.00 (1.00 to 5.00)
Visit 6 - Second Intervention	4.00 (2.00 to 5.00)	4.00 (2.00 to 6.00)
Visit 7 - Second Intervention	4.00 (2.00 to 4.00)	3.00 (2.00 to 5.00)
Visit 8 - Second Intervention	3.00 (3.00 to 5.00)	4.00 (1.00 to 5.00)

Population analysed: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

Primary outcome: Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale

Time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends. Median (Inter-Quartile Range). Unit: units on a scale

Measure	Placebo First, Then rhIGF-1 n = 15	rhIGF-1 First, Then Placebo n = 15
Visit 1 - First Intervention	6.00 (5.00 to 8.00)	4.00 (2.00 to 8.00)
Visit 2 - First Intervention	5.00 (3.00 to 7.00)	5.00 (3.00 to 7.00)
Visit 3 - First Intervention	5.00 (4.00 to 7.00)	4.00 (2.00 to 7.00)
Visit 4 - First Intervention	6.00 (3.00 to 7.00)	4.00 (3.00 to 7.00)
Visit 5 - First Intervention	5.00 (2.00 to 6.00)	3.00 (2.00 to 5.00)
Visit 6 - Second Intervention	4.00 (3.00 to 5.00)	4.00 (3.00 to 6.00)
Visit 7 - Second Intervention	4.00 (2.00 to 7.00)	4.00 (3.00 to 5.00)
Visit 8 - Second Intervention	4.00 (2.00 to 6.00)	4.00 (3.00 to 5.00)

Population analysed: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

Primary outcome: Clinical Global Impression - Severity (CGI-S)

Time frame: Every 10 weeks during each of the two 20-week treatment periods. Median (Inter-Quartile Range). Unit: units on a scale

Measure	Placebo First, Then rhIGF-1 n = 15	rhIGF-1 First, Then Placebo n = 15
Visit 1 - First Intervention	4.00 (4.00 to 4.00)	4.00 (3.00 to 4.00)
Visit 3 - First Intervention	4.00 (3.00 to 4.00)	4.00 (4.00 to 4.00)
Visit 5 - First Intervention	4.00 (4.00 to 4.00)	4.00 (4.00 to 5.00)
Visit 6 - Second Intervention	4.00 (3.00 to 4.00)	4.00 (4.00 to 5.00)
Visit 8 - Second Intervention	4.00 (3.00 to 4.00)	4.00 (4.00 to 5.00)
Visit 10 - Second Intervention	4.00 (4.00 to 4.00)	4.50 (4.00 to 5.00)

Population analysed: One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Primary outcome: Clinical Global Impression - Improvement (CGI-I)

Time frame: Every 10 weeks during each of the two 20-week treatment periods. Median (Inter-Quartile Range). Unit: units on a scale

Measure	Placebo First, Then rhIGF-1 n = 15	rhIGF-1 First, Then Placebo n = 15
Visit 3 - First Intervention	4.00 (4.00 to 4.00)	4.00 (4.00 to 4.00)
Visit 5 - First Intervention	4.00 (4.00 to 4.00)	4.00 (4.00 to 4.00)
Visit 6 - Second Intervention	4.00 (3.00 to 5.00)	4.00 (4.00 to 5.00)
Visit 8 - Second Intervention	4.00 (4.00 to 4.00)	4.00 (4.00 to 5.00)
Visit 10 - Second Intervention	4.00 (3.00 to 4.00)	4.00 (3.00 to 5.00)

Population analysed: Data was not collected at Visit 1 because participants had not yet been exposed to either intervention. One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 80 weeks (from screening visit to 12-week follow up phone call).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	4 of 30 (13.3%)	16 of 30 (53.3%)	0 of 30
rhIGF-1	4 of 30 (13.3%)	20 of 30 (66.7%)	0 of 30
Off Treatment	2 of 30 (6.7%)	15 of 30 (50%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24623853Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.
Background: PubMed 8506830Schultz RJ, Glaze DG, Motil KJ, Armstrong DD, del Junco DJ, Hubbard CR, Percy AK. The pattern of growth failure in Rett syndrome. Am J Dis Child. 1993 Jun;147(6):633-7. doi: 10.1001/archpedi.1993.02160300039018.
Background: PubMed 16865103Williamson SL, Christodoulou J. Rett syndrome: new clinical and molecular insights. Eur J Hum Genet. 2006 Aug;14(8):896-903. doi: 10.1038/sj.ejhg.5201580.
Background: PubMed 16940240Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Silvestri JM, Ramirez JM. Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr Res. 2006 Oct;60(4):443-9. doi: 10.1203/01.pdr.0000238302.84552.d0. Epub 2006 Aug 28.
Background: PubMed 12112736Percy AK. Clinical trials and treatment prospects. Ment Retard Dev Disabil Res Rev. 2002;8(2):106-11. doi: 10.1002/mrdd.10022.
Background: PubMed 10508514Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. doi: 10.1038/13810.
Background: PubMed 9620804Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998 May 28;393(6683):386-9. doi: 10.1038/30764.
Background: PubMed 11809720Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet. 2002 Jan 15;11(2):115-24. doi: 10.1093/hmg/11.2.115.
Background: PubMed 12727440Cohen DR, Matarazzo V, Palmer AM, Tu Y, Jeon OH, Pevsner J, Ronnett GV. Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci. 2003 Apr;22(4):417-29. doi: 10.1016/s1044-7431(03)00026-5.
Background: PubMed 16199017Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM. Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry. 2006 Mar 1;59(5):468-76. doi: 10.1016/j.biopsych.2005.07.025. Epub 2005 Sep 30.
Background: PubMed 11242117Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001 Mar;27(3):322-6. doi: 10.1038/85899.
Background: PubMed 12160743Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron. 2002 Jul 18;35(2):243-54. doi: 10.1016/s0896-6273(02)00768-7.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mustafa Sahin, MD, PhD principal investigator

Boston Children's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Recombinant Human Insulin Growth Factor 1 (rhIGF-1) in people with Rett Syndrome, run by Boston Children's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale (time frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01777542, which also lists 57 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2018.