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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

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.


Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Asperger Syndrome Aspergers Syndrome Drug: Milnacipran Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
Study Start Date : February 2011
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Milnacipran 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

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




Primary Outcome Measures :
  1. 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.


  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01337700


Locations
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United States, New York
Montefiore Medical Center, Albert Einstein College of Medicine
Bronx, New York, United States, 10467
Sponsors and Collaborators
Montefiore Medical Center
Forest Laboratories
Investigators
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Principal Investigator: Eric Hollander, MD Montefiore Medical Center/Albert Einstein College of Medicine
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Responsible Party: Eric Hollander, Clinical Professor, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT01337700    
Other Study ID Numbers: 10-09-299
First Posted: April 19, 2011    Key Record Dates
Results First Posted: February 27, 2020
Last Update Posted: February 27, 2020
Last Verified: February 2020
Keywords provided by Eric Hollander, Montefiore Medical Center:
ASD
Autism
Autism Spectrum Disorder
Asperger Syndrome
Asperger
PDD
PDD-NOS
Additional relevant MeSH terms:
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Syndrome
Autistic Disorder
Autism Spectrum Disorder
Asperger Syndrome
Disease
Pathologic Processes
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Milnacipran
Levomilnacipran
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Psychotropic Drugs