Early Intervention With Fluoxetine in 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. Identifier: NCT00183339
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : March 26, 2014
Last Update Posted : March 26, 2014
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill

September 6, 2005
September 16, 2005
September 10, 2013
March 26, 2014
March 26, 2014
July 2005
February 2008   (Final data collection date for primary outcome measure)
Rate of Recruitment [ Time Frame: 19 months ]
In order for a larger trial with similar design to be feasible a number of factors needed to be examined. The first was whether families would enroll very young children with ASD into a year long blinded medication study. To determine this we examined the average number of months to randomize 1 participant per site. We calculated this (as total # months required for recruitment* 2sites ) /[ # participants randomized ] and compared it to the typical # of months required to recruit an older child with ASD for a double-blind 12 week placebo controlled medication study, which is typically about 1.2 months at each of the sites involved in the study.
Growth curve on the Pervasive Developmental Disorder Behavior Inventory-Parent Version (PDDBIp)subscales; measured over 12 months
Complete list of historical versions of study NCT00183339 on Archive Site
  • Rate of Attrition [ Time Frame: Measured at Month 12 ]
    The percentage of participants who discontinued treatment prior to completion of the 12 month study
  • Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire [ Time Frame: 12 months ]
    This is a caregiver completed measure that assesses the extent to which the caregiver feels care of the participant influences the caregiver's and other family members' emotional states and/or activities. There are a total of 22 items rated from 1 - not at all to 5 - very much (with one item reverse scored). Total score is the sum of all the items (with one item reverse scored). There are three subscales objective strain -12 items, internalized subjective strain 6 items, externalized subjective 4 items. The total score can range from a minimum of 0 - no strain at all, to 110 all items rated as very much.
  • Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I) [ Time Frame: 12 months ]
    The Aberrant Behavior Checklist (ABC) is a caregiver completed rating scale that assesses problem behaviors frequently seen in individuals with developmental disabilities. There are a total of 58 items on 5 subscales that are rated from 0 - not at all a problem to 3 - problem is severe in degree. The ABC-I consists of 15 items that reflect mood swings, self-injury and aggression. The subscale score is the sum of the score on each of the 15 items. The minimum score on the ABC-I is 0 and the maximum score is 45. Higher scores reflect more severe behavioral problems. A score > or = to 18 is generally considered clinically significant.
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Early Intervention With Fluoxetine in Autism
A Randomized, Placebo-controlled Trial of Fluoxetine in Preschool Children
This study is a pilot study to evaluate the feasibility and safety of conducting a year long, double-blind, placebo-controlled trial of fluoxetine in pre-school children to enhance developmental processes in core areas impacted by autism.

Autism, a brain disorder that affects a small percentage of Americans, often results in a lifetime of impaired thinking, feeling, and social functioning. The disorder generally becomes apparent in children by the age of 3. Autism typically affects a person's ability to communicate, form relationships with others, and respond appropriately to the external world. Some people with autism can function at a relatively high level, with speech and intelligence intact. Others have serious cognitive impairments and language delays, and some never speak. This study will assess the safety and effectiveness of treating autistic children with fluoxetine to enhance developmental processes in core areas impacted by autism.

Each participant was randomly assigned to treatment with double-blinded placebo or fluoxetine for 12 months. After initial screening and randomization, participants were assessed every two weeks for approximately the first 3 months, or until the dose of medication is stabilized. After this initial period, they were assessed on a monthly basis. Dosing was flexible as determined by the adverse and beneficial responses to treatment although there was a suggested titration schedule.

Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Autistic Disorder
  • Drug: Fluoxetine
    Between 2 mg per day and 20 mg per day of liquid fluoxetine will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule.
    Other Name: Prozac
  • Drug: Placebo
    Between 0.5ml per day and 5ml per day of liquid placebo will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule.
  • Placebo Comparator: Placebo
    Placebo, liquid solution flexible dose 0.5 to 5ml every morning (AM)
    Intervention: Drug: Placebo
  • Experimental: fluoxetine
    Fluoxetine, 20mg/5ml solution, flexible dose 0.5 to 5ml every AM
    Intervention: Drug: Fluoxetine
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
February 2008
February 2008   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of autism

Exclusion Criteria:

  • Diagnosis of Asperger Syndrome, Rett Syndrome, Childhood Disintegrative Disorder, or Pervasive Development Disorder-Not Otherwise Specified
  • Informed that treatment with a selective serotonin reuptake inhibitor (SSRI) is medically inadvisable
  • Need for ongoing psychotropic medication (except for diphenhydramine, clonidine, or melatonin for sleep)
  • Recent use of stimulants within 5 days prior to enrollment
  • Ongoing need for or recent use of most psychotropic medications within 14 days of enrollment
  • Recent initiation of specialized educational, behavioral, or diet intervention for autism in the month prior to enrollment
Sexes Eligible for Study: All
30 Months to 58 Months   (Child)
Contact information is only displayed when the study is recruiting subjects
United States
U54MH066418( U.S. NIH Grant/Contract )
U54MH066418 ( U.S. NIH Grant/Contract )
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Linmarie Sikich, MD, University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Study Chair: Linmarie Sikich, MD University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
February 2014

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