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.

Study Overview

• Status: Completed
• Conditions: Autistic Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Fluoxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 25714
      • University of North Carolina, Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo, liquid solution flexible dose 0.5 to 5ml every morning (AM)	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.
Experimental: fluoxetine; Fluoxetine, 20mg/5ml solution, flexible dose 0.5 to 5ml every AM	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 Names: Prozac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Recruitment	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.	19 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Attrition	The percentage of participants who discontinued treatment prior to completion of the 12 month study	Measured at Month 12
Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire	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.	12 months
Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I)	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.	12 months

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Linmarie Sikich, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: February 7, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Autism
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: U54MH066418 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No