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

Phase 4

Completed

Conditions: Asperger Syndrome
Aspergers Syndrome
Autism Spectrum Disorder

Interventions: Drug: Milnacipran
Drug: Placebo

Registration Number: NCT01337700

Lead Sponsor: Montefiore Medical Center

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Milnacipran	Milnacipran	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale	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	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.

Secondary Outcome Measures

Name	Time	Method
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale	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	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)	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.