Autistic Disorder
Conditions
Keywords
Autism
Brief summary
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.
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.
Interventions
DRUGFluoxetine
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.
DRUGPlacebo
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.
Sponsors
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Months to 58 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Recruitment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Attrition | 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 | 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will take the placebo | 10 |
| Fluoxetine Participants will take liquid fluoxetine 2-20 mg | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | Fluoxetine | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 18 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 42.6 months STANDARD_DEVIATION 8.1 | 43.4 months STANDARD_DEVIATION 7.4 | 44.0 months STANDARD_DEVIATION 6.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 18 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 7 / 8 |
| serious Total, serious adverse events | 1 / 10 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 19 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Rate of Recruitment | 2.1 months/participant at 1 site |
| Fluoxetine | Rate of Recruitment | 2.1 months/participant at 1 site |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire | 0.8 units on a scale | Standard Deviation 2.5 |
| Fluoxetine | Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire | -1.86 units on a scale | Standard Deviation 2.3 |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I) | -0.70 units on a scale | Standard Deviation 2.9 |
| Fluoxetine | Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I) | -8.50 units on a scale | Standard Deviation 10.6 |
Secondary
Rate of Attrition
The percentage of participants who discontinued treatment prior to completion of the 12 month study
Time frame: Measured at Month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Rate of Attrition | 60 percent of group that discontinued early |
| Fluoxetine | Rate of Attrition | 50 percent of group that discontinued early |