Autism Spectrum DisorderPhase 4NCT01337700
Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
A Phase 4 study testing Milnacipran in people with Autism Spectrum Disorder and Asperger Syndrome, run by Montefiore Medical Center at 1 site in United States.
Trial summary
Autism Spectrum Disorders (ASD) include Autistic disorder, Asperger's syndrome and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). These are developmental disorders beginning prior to three years of age. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Autism Spectrum Disorder, Asperger Syndrome, Aspergers Syndrome
- What is being tested?
- Milnacipran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Jul 2014
- Phase
- Phase 4
- 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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and Female patients
- Aged 18-50 years
- Diagnosis of Autism Spectrum Disorder
- intelligence quotient greater than 70
Who cannot join
- Pregnant subjects
- Patients deemed by comprehensive psychiatric interview to have a significant risk of suicide
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center, Albert Einstein College of Medicine
The Bronx, New York, 10467
About this study
Autism Spectrum Disorders (ASD) include Autistic disorder, Asperger's syndrome and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). These are developmental disorders beginning prior to three years of age. Recent Centers for Disease Control (CDC) estimates suggest that ASD affects up to 1 in 100 individuals and up to 1 in 50 boys. There are very substantial costs associated with caring for patients with ASD, and ASD has the highest Caregiver Burden Scores of any condition. There are three core symptom domains of ASD, including social deficits, repetitive behaviors and language deficits. Patients can also have associated symptoms of attentional deficits, disruptive behaviors and intellectual disability. There is currently no Food and Drug administration (FDA) approved treatment for the core symptoms of autism, but risperidone and aripiprazole have FDA approval for disruptive behaviors associated with autism.
This is a 12 week randomized double blind placebo controlled trial of Milnacipran in adults with ASD or Aspergers Syndrome. Milnacipran is said to play a role in the activation and normalization of the locus coeruleus-noradrenergic system, of which is hypothesized to play a role in behavior adaptations and performance.
- Being tested
- Milnacipran, Placebo
- Keywords
- ASD, Autism, Autism Spectrum Disorder, Asperger Syndrome, Asperger, PDD, PDD-NOS
- Medical subject headings
- Autism Spectrum Disorder, Asperger Syndrome, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilnacipranDrug
Also called Savella
Patients will receive a titrated dose of milnacipran increasing to a maximum of 100mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.
PlaceboDrug
Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
| Study group | Role | What they receive |
|---|---|---|
| Milnacipran | Experimental | Not described Receives: Drug: Milnacipran |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale
Change will be measured in each subject's score on the Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale from baseline through study end (week 12).Higher values represent a worse outcome.
The raw scores are converted to T-scores for each scale and sub-scale which are then compared against the mean. Higher values represent a worse outcome. A T-score of 50 is the mean of a relevant reference population. A T-score above 65 indicates a moderate to severe problem. For example, Row 1 is the mean of baseline T-scores for the Inattention/ Memory subscale and Row 2 is the mean of week 12 T-scores for the Inattention/ Memory subscale. The difference between these two means is used to measure the change from baseline through week 12 for both the groups.
Measured: Baseline and Week 12 scores
Change in Hyperactivity as Measured by Aberrant Behavior Checklist - Hyperactivity Scale
The Aberrant Behavior Checklist is an informant-based questionnaire consisting of 58 items subdivided amongst 5 scales: irritability, lethargy and social withdrawal, stereotypic behavior, hyperactivity/non-compliance, and inappropriate speech [34]. A score for each item ranges from 0 indicating "no problem" to 3 indicating "severe problem". Scale scores are calculated by summing the items within that scale. Higher scores indicate greater impairment.Reported Data is for change in ABC-H from baseline to endpoint (week 0 to week 12).This data is specifically looking at the hyperactivity scale which is 16 items with each item ranging from 0-3 making total scores 0-48.
Measured: Baseline to Endpoint - 12 weeks
Secondary outcomes (3)
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale
The CGI-I reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from Much Improved (1) to Much worse (5).
Measured: screening, baseline, weeks 2,4,6,8,10,12
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale
This scale has been shown to be a sensitive outcome measure in autism trials of repetitive behaviors. Data for secondary outcome not analyzed due to lack of significance in primary outcomes measured.
- scale range: 0 - 40 total, 0 - 7 subclinical, 8-15 mild, 16 - 23 moderate, 24 - 31 severe, 32 - 40 extreme
- score interpretation: Higher overall scores reflect increasing symptom severity.
Measured: baseline, weeks 2,4,6,8,10,12
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF)
This scale is shown to be sensitive to change in adults with autism, and related to amygdala function. Higher scores mean a better outcome.A clinical tool measuring emotion recognition through facial expression, voice and posture.
- Child faces 2 (range 0 - 100, higher values reflecting higher % of errors)
- Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors)
- Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors)
- Adult paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) Errors are counted and organized by pre-determined affect and intensity. Subtests considered separately.
Measured: baseline, weeks 2,4,6,8,10,12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2011 (estimated)
- Study startFeb 2011
- Primary completionJul 2014
- Study completionJul 2014
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.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Principal investigator, Eric Hollander, Montefiore Medical Center
- Investigators
- Eric Hollander, MD, Principal investigator, Montefiore Medical Center/Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01337700
- Sponsor's protocol ID
- 10-09-299
- Status last verified
- Feb 2020
- First submitted
- 27 Dec 2010
- Last updated
- 27 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
- ClinicalTrials.gov ID
- NCT01337700
- Acronym / sponsor ID
- 10-09-299
- Keywords
- ASD, Autism, Autism Spectrum Disorder, Asperger Syndrome, Asperger, PDD, PDD-NOS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Feb 2011
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 19 Apr 2011 (estimated)
- Results
- Posted 27 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autism Spectrum Disorders (ASD) include Autistic disorder, Asperger's syndrome and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). These are developmental disorders beginning prior to three years of age. Recent Centers for Disease Control (CDC) estimates suggest that ASD affects up to 1 in 100 individuals and up to 1 in 50 boys. There are very substantial costs associated with caring for patients with ASD, and ASD has the highest Caregiver Burden Scores of any condition. There are three core symptom domains of ASD, including social deficits, repetitive behaviors and language deficits. Patients can also have associated symptoms of attentional deficits, disruptive behaviors and intellectual disability. There is currently no Food and Drug administration (FDA) approved treatment for the core symptoms of autism, but risperidone and aripiprazole have FDA approval for disruptive behaviors associated with autism.
This is a 12 week randomized double blind placebo controlled trial of Milnacipran in adults with ASD or Aspergers Syndrome. Milnacipran is said to play a role in the activation and normalization of the locus coeruleus-noradrenergic system, of which is hypothesized to play a role in behavior adaptations and performance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Milnacipran | Experimental | Drug: Milnacipran |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male and Female patients
- Aged 18-50 years
- Diagnosis of Autism Spectrum Disorder
- intelligence quotient greater than 70
Key exclusion criteria (2 listed)
- Pregnant subjects
- Patients deemed by comprehensive psychiatric interview to have a significant risk of suicide
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 |
|---|---|---|
| MilnacipranAlso: SavellaPatients will receive a titrated dose of milnacipran increasing to a maximum of 100mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile. | Drug | Milnacipran |
| PlaceboSubjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg. | Drug | Placebo |
Primary outcome
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale
Time frame: Baseline and Week 12 scores
Change will be measured in each subject's score on the Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale from baseline through study end (week 12).Higher values represent a worse outcome. The raw scores are converted to T-scores for each scale and sub-scale which are then compared against the mean. Higher values represent a worse outcome. A T-score of 50 is the mean of a relevant reference population. A T-score above 65 indicates a moderate to severe problem. For example, Row 1 is the mean of baseline T-scores for the Inattention/ Memory subscale and Row 2 is the mean of week 12 T-scores for the Inattention/ Memory subscale. The difference between these two means is used to measure the change from baseline through week 12 for both the groups.
Change in Hyperactivity as Measured by Aberrant Behavior Checklist - Hyperactivity Scale
Time frame: Baseline to Endpoint - 12 weeks
The Aberrant Behavior Checklist is an informant-based questionnaire consisting of 58 items subdivided amongst 5 scales: irritability, lethargy and social withdrawal, stereotypic behavior, hyperactivity/non-compliance, and inappropriate speech [34]. A score for each item ranges from 0 indicating "no problem" to 3 indicating "severe problem". Scale scores are calculated by summing the items within that scale. Higher scores indicate greater impairment.Reported Data is for change in ABC-H from baseline to endpoint (week 0 to week 12).This data is specifically looking at the hyperactivity scale which is 16 items with each item ranging from 0-3 making total scores 0-48.
3 secondary outcomes
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale
Time frame: screening, baseline, weeks 2,4,6,8,10,12
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale
Time frame: baseline, weeks 2,4,6,8,10,12
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF)
Time frame: baseline, weeks 2,4,6,8,10,12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eric Hollander, MD principal investigator
Montefiore Medical Center/Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Milnacipran in people with Autism Spectrum Disorder and Asperger Syndrome, run by Montefiore Medical Center 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 2 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 27 Feb 2020. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 27 Feb 2020). 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?
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale (time frame: Baseline and Week 12 scores). The study lists 2 primary outcomes in all. 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 27 Feb 2020.