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Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01337700
Recruitment Status : Completed
First Posted : April 19, 2011
Results First Posted : February 27, 2020
Last Update Posted : February 27, 2020
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Eric Hollander, Montefiore Medical Center

Tracking Information
First Submitted Date  ICMJE December 27, 2010
First Posted Date  ICMJE April 19, 2011
Results First Submitted Date  ICMJE March 17, 2016
Results First Posted Date  ICMJE February 27, 2020
Last Update Posted Date February 27, 2020
Study Start Date  ICMJE February 2011
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2020)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale [ Time Frame: Baseline through Week 12 ]
Change will be measured in each subject's score on the Conners from baseline through study end (week 12). It is a clinically expert rating scale used to measure attention dysfunction. It offers good psychometric properties and psychopathological item content focused on inattention, impulsivity and hyperactivity. Change in subjects on placebo, will be compared to those receiving the study drug.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2020)
  • Change in Autism Severity Levels Based on the Clinical Global Impressions Scale [ Time Frame: screening, baseline, weeks 2,4,6,8,10,12 ]
    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).
  • Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale [ Time Frame: baseline, weeks 2,4,6,8,10,12 ]
    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.
  • Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) [ Time Frame: baseline, weeks 2,4,6,8,10,12 ]
    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.
    1. Child faces 2 (range 0 - 100, higher values reflecting higher % of errors)
    2. Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors)
    3. Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors)
    4. 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
  • Aberrant Behavior Checklist - Irritability Scale [ Time Frame: Screening, baseline, weeks 2,4,6,8,10,12 ]
    Rating scale sensitive to changes in disruptive behaviors in autism.
  • Yale-Brown Obsessive Compulsive Scale (YBOCS)- Compulsion Subscale [ Time Frame: screening, baseline, weeks, 2,4,6,8,10,12 ]
    Clinical tool used to measure repetitive behaviors in autism trials.
  • Diagnostic Analysis of Nonverbal Activity-2 (DANVA-2) [ Time Frame: screening, baseline, weeks 2,4,6,8,10,12 ]
    Tool used to measure social cognition in adults with autism, as related to amygdala function.
  • NoGo-Go Task During functional Magnetic Resonance Imaging (fMRI) [ Time Frame: Baseline and Week 12 ]
    A neurocognitive task of motor inhibition measured during the fMRI.
  • Core Autism Treatment Scale - Severity and Improvement [ Time Frame: screening, baseline, weeks 2, 4, 6, 8, 10, 12 ]
    Tool used to compare pretreatment ratings of severity and post treatment ratings of improvement after the start of therapy.
  • Clinical Global Impressions Scale (CGI) [ Time Frame: screening, baseline, weeks 2,4,6,8,10,12 ]
    A scale that measures improvement based off of the clinician's interpretations.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
Official Title  ICMJE Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
Brief 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. 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Autism Spectrum Disorder
  • Asperger Syndrome
  • Aspergers Syndrome
Intervention  ICMJE
  • Drug: Milnacipran
    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.
    Other Name: Savella
  • Drug: Placebo
    Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Study Arms  ICMJE
  • Experimental: Milnacipran
    Intervention: Drug: Milnacipran
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2014)
10
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2011)
34
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and Female patients
  • Aged 18-50 years
  • Diagnosis of Autism Spectrum Disorder
  • intelligence quotient greater than 70

Exclusion Criteria:

  • Pregnant subjects
  • Patients deemed by comprehensive psychiatric interview to have a significant risk of suicide
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01337700
Other Study ID Numbers  ICMJE 10-09-299
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eric Hollander, Montefiore Medical Center
Study Sponsor  ICMJE Montefiore Medical Center
Collaborators  ICMJE Forest Laboratories
Investigators  ICMJE
Principal Investigator: Eric Hollander, MD Montefiore Medical Center/Albert Einstein College of Medicine
PRS Account Montefiore Medical Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP