Rett SyndromePhase 1NCT02562820
An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome
A Phase 1 study testing Intravenous infusion in people with Rett Syndrome, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Rett Syndrome (RTT) is a complex disorder resulting from mutations in a gene encoding the MeCP2 protein. Currently, there are no methods to fix the abnormal gene, however, animal studies suggest that the symptoms of RTT can be treated. Ketamine is a sedative or anesthetic, depending on the dose. Read more about this study
- Who is it for?
- Ages 5 to 25 years, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Intravenous infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 5 to 25 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Rett syndrome diagnosis based on the 2010 RTT diagnostic criteria, as determined by review of clinical records, and
- Pathogenic mutation in the MECP2 gene, and
- Breathing score of 3 or greater on RSBQ, and
- Age 5-25 years.
Who cannot join
- Ongoing clinical regression as determined by review of clinical records and consultation with parents, or
- Seizure within one week of study session, or
- Unstable systemic illness other than Rett syndrome, or
- Clinically important variations in medication use.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
Rett Syndrome (RTT) is a complex disorder resulting from mutations in a gene encoding the MeCP2 protein. Currently, there are no methods to fix the abnormal gene, however, animal studies suggest that the symptoms of RTT can be treated.
Ketamine is a sedative or anesthetic, depending on the dose. The drug is approved by the US Food and Drug Administration (FDA) and is commonly used in children and adults. Animal studies and case reports in humans suggest that ketamine may reduce the symptoms of Rett syndrome. The purpose of this study is to determine the safety and efficacy of ketamine for treating breathing and behavioral symptoms of RTT.
Read the detailed description
Families will be asked to maintain current prescription medications during the expected three-month duration of the study. However, clinically indicated medication alterations will naturally be permitted and recorded.
Each participant will experience four study days, separated by about a month. On three of the study days participants will be given Ketamine, and on the other day they will be given saline placebo.
Studies will be conducted in the Cleveland Clinic's General Clinical Research Unit which is an NIH-sponsored unit designed for studies such as this. Subjects will be admitted on the first day of each study sequence, and discharged the subsequent day. Study subjects will arrive at approximately 8:00 AM. Age, weight and height will be determined and prescription medications will be recorded. Subjects will be fitted with sensors for recording respiration, heart rate and brain electrical activity (electroencephalogram, or EEG). Treatment administration will start at noon. To avoid potential effects of circadian variation, treatment administration will start at the same time for each study day in each subject. Because the half-life of Ketamine is short (t1/2 = 10-15 minutes for sedation/anesthesia), we expect participating patients to be fully recovered from any potential sedating effects of Ketamine within an hour or two.
Each subject will be randomized to receive 3 of the 5 doses of Ketamine 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg] plus placebo, for a total of 4 periods (visits). Ordering of the treatments will be randomized, with patients earlier in the study to receive lower doses of Ketamine.
The study drug will be given as a constant infusion at 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg over the course of 40 minutes.
Apnea/breath-hold index, hyperventilation and cardio-respiratory coupling indices will be measured by polysomnography (PSG) before, during and after each treatment.
EEG will be recorded before, during and after each treatment.
Auditory evoked potentials (AEP) will be recorded on the day after each treatment.
Rett Syndrome Behavior Questionnaire (RSBQ) will be administered multiple times after each treatment, first in the hospital and then at home.
Repetitive Behavior Scale-Revised (RBSR) will be administered on the day after each treatment.
Before infusion and one hour after infusion, a few mL of peripheral blood will be sampled to measure bio-markers. Blood will be centrifuged and plasma will be frozen for subsequent analysis.
- Conditions
- Rett Syndrome
- Being tested
- Intravenous infusion
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous infusionProcedure or surgery
Intravenous infusion of Ketamine
Intravenous infusionProcedure or surgery
Intravenous infusion of Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Subjects will receive intravenous infusion of a 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg dose over the course of 40 minutes Receives: Procedure: Intravenous infusion |
| Placebo | Placebo comparator | Subjects will receive an intravenous infusion of normal saline over the course of 40 minutes Receives: Procedure: Intravenous infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Behavioral phenomena requiring intervention
Occurrence of agitation, irritability, or worsening of pre-existing symptoms.
Measured: From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.
Secondary outcomes (1)
Exploratory - Rett Syndrome Behavior Questionnaire (RSBQ)
A formal score obtained by administering the RSBQ to the subject's parent/guardian before and after every study visit.
Measured: On the day following study drug infusion at each visit (30 - 36 hours after admission for each visit).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2015 (estimated)
- Study startNov 2015
- Primary completionJul 2017
- Study completionJul 2017
Why it stopped: Funding withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Sessler, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02562820
- Sponsor's protocol ID
- 15-627
- Status last verified
- Aug 2017
- First submitted
- 28 Sep 2015
- Last updated
- 30 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
- ClinicalTrials.gov ID
- NCT02562820
- Acronym / sponsor ID
- 15-627
- Conditions
- Rett Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding withdrawn
- Enrolment
- 4 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 29 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rett Syndrome (RTT) is a complex disorder resulting from mutations in a gene encoding the MeCP2 protein. Currently, there are no methods to fix the abnormal gene, however, animal studies suggest that the symptoms of RTT can be treated.
Ketamine is a sedative or anesthetic, depending on the dose. The drug is approved by the US Food and Drug Administration (FDA) and is commonly used in children and adults. Animal studies and case reports in humans suggest that ketamine may reduce the symptoms of Rett syndrome. The purpose of this study is to determine the safety and efficacy of ketamine for treating breathing and behavioral symptoms of RTT.
Detailed description
Families will be asked to maintain current prescription medications during the expected three-month duration of the study. However, clinically indicated medication alterations will naturally be permitted and recorded.
Each participant will experience four study days, separated by about a month. On three of the study days participants will be given Ketamine, and on the other day they will be given saline placebo.
Studies will be conducted in the Cleveland Clinic's General Clinical Research Unit which is an NIH-sponsored unit designed for studies such as this. Subjects will be admitted on the first day of each study sequence, and discharged the subsequent day. Study subjects will arrive at approximately 8:00 AM. Age, weight and height will be determined and prescription medications will be recorded. Subjects will be fitted with sensors for recording respiration, heart rate and brain electrical activity (electroencephalogram, or EEG). Treatment administration will start at noon. To avoid potential effects of circadian variation, treatment administration will start at the same time for each study day in each subject. Because the half-life of Ketamine is short (t1/2 = 10-15 minutes for sedation/anesthesia), we expect participating patients to be fully recovered from any potential sedating effects of Ketamine within an hour or two.
Each subject will be randomized to receive 3 of the 5 doses of Ketamine 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg] plus placebo, for a total of 4 periods (visits). Ordering of the treatments will be randomized, with patients earlier in the study to receive lower doses of Ketamine.
The study drug will be given as a constant infusion at 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg over the course of 40 minutes.
Apnea/breath-hold index, hyperventilation and cardio-respiratory coupling indices will be measured by polysomnography (PSG) before, during and after each treatment.
EEG will be recorded before, during and after each treatment.
Auditory evoked potentials (AEP) will be recorded on the day after each treatment.
Rett Syndrome Behavior Questionnaire (RSBQ) will be administered multiple times after each treatment, first in the hospital and then at home.
Repetitive Behavior Scale-Revised (RBSR) will be administered on the day after each treatment.
Before infusion and one hour after infusion, a few mL of peripheral blood will be sampled to measure bio-markers. Blood will be centrifuged and plasma will be frozen for subsequent analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Procedure: Intravenous infusionSubjects will receive intravenous infusion of a 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg dose over the course of 40 minutes |
| Placebo | Placebo comparator | Procedure: Intravenous infusionSubjects will receive an intravenous infusion of normal saline over the course of 40 minutes |
Who may qualify
- Ages
- 5 to 25 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Rett syndrome diagnosis based on the 2010 RTT diagnostic criteria, as determined by review of clinical records, and
- Pathogenic mutation in the MECP2 gene, and
- Breathing score of 3 or greater on RSBQ, and
- Age 5-25 years.
Key exclusion criteria (4 listed)
- Ongoing clinical regression as determined by review of clinical records and consultation with parents, or
- Seizure within one week of study session, or
- Unstable systemic illness other than Rett syndrome, or
- Clinically important variations in medication use.
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 |
|---|---|---|
| Intravenous infusionIntravenous infusion of Ketamine | Procedure or surgery | Ketamine |
| Intravenous infusionIntravenous infusion of Normal Saline | Procedure or surgery | Placebo |
Primary outcome
Behavioral phenomena requiring intervention
Time frame: From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.
Occurrence of agitation, irritability, or worsening of pre-existing symptoms.
1 secondary outcome
Exploratory - Rett Syndrome Behavior Questionnaire (RSBQ)
Time frame: On the day following study drug infusion at each visit (30 - 36 hours after admission for each visit).
Results and safety
The study was stopped early (reason given: Funding withdrawn). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2017.
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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.
Daniel Sessler, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous infusion in people with Rett Syndrome, run by The Cleveland Clinic 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 4 inclusion and 4 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: stopped early, as of the sponsor's last update on 30 Aug 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Funding withdrawn). Results are not available in the source record.
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?
Behavioral phenomena requiring intervention (time frame: From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Aug 2017; AzTrials last refreshed its copy on 8 Nov 2026.