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

NCT01337700 | Completed Phase 4 Results DMC

• 1 other identifier: 10-09-299
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder; Asperger Syndrome; Aspergers Syndrome

Keywords

ASD; Autism; Autism Spectrum Disorder; Asperger Syndrome; Asperger; PDD; PDD-NOS

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline to Endpoint - 12 weeks

Secondary Outcomes (3)

• Change in Autism Severity Levels Based on the Clinical Global Impressions Scale

  screening, baseline, weeks 2,4,6,8,10,12

• Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale

  baseline, weeks 2,4,6,8,10,12

• Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF)

  baseline, weeks 2,4,6,8,10,12

Study Arms (2)

Milnacipran

EXPERIMENTAL

Drug: Milnacipran

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Milnacipran DRUG

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.

Also known as: Savella

Milnacipran

Placebo DRUG

Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Pregnant subjects
• Patients deemed by comprehensive psychiatric interview to have a significant risk of suicide

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Forest Laboratories: collaborator

Study Sites (1)

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Asperger Syndrome; Autistic Disorder

Interventions

Milnacipran

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Eric Hollander, MD
• Organization: Montefiore Medical Center, Albert Eins

eholland@montefiore.org

7189204287

Study Officials

• Eric Hollander, MD

  Montefiore Medical Center/Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 27, 2010
• First Posted: April 19, 2011
• Study Start: February 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 27, 2020
• Results First Posted: February 27, 2020

Record last verified: 2020-02

Locations

US (1)