A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness and tolerability of aripiprazole in the treatment of children and adolescents with Fragile X Syndrome.

Detailed Description
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This 12-week prospective, open-label study design was chosen to gather pilot data for potential future lager scale, double-blind, placebo-controlled studies in Fragile X Syndrome. We hypothesize that aripiprazole will be effective in decreasing aggression, SIB, agitation, and interfering repetitive behavior commonly observed in individuals with Fragile X Syndrome. We also hypothesize that aripiprazole will be well tolerated.

Official Title
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Aripiprazole in Fragile X Syndrome

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 5 and 35 years and Body weight greater than or equal to 15 kg Confirmed diagnosis of Fragile X Syndrome based upon genetic testing results. Outpatients. Psychotropic medication-free for at least 2 weeks prior to screening laboratory tests and electrocardiogram. (Except 5 weeks for fluoxetine and 4 weeks for all typical and atypical antipsychotics that have been administered for at least a 4 week period.) Exceptions to medication-free status will include drugs given at bedtime targeting insomnia. Such drugs may include melatonin, clonidine, chloral hydrate, diphenhydramine, ramelteon, benzodiazepines, or other sedative-hypnotics. Clinical Global Impression Scale Severity score (CGI-S) of at greater than or equal to 4 (Moderately Ill) A score of at greater than or equal to 18 on the Irritability subscale of the Aberrant Behavior Checklist (ABC) at screen and baseline. Mental age of greater than or equal to 18 months as measured by the Wechsler, revised Leiter, or Mullen tests Each subject must be in good physical health as determined by screening procedures which will include a detailed medical history, complete physical and neurological examination. Exclusion Criteria: DSM-IV diagnosis of schizophrenia, another psychotic disorder, bipolar disorder or alcohol or other substance abuse within the last 6 months. A significant medical condition such as heart, liver, renal or pulmonary disease, or an actively treated seizure disorder, as determined by history, physical examination or laboratory testing. Subjects with an unstable seizure disorder will be excluded. Females with a positive urine pregnancy test. Evidence of a prior adequate trial of aripiprazole (defined as a duration of greater than or equal to 2 weeks at a dose of at least 5 mg per day). When there is not evidence of a prior adequate trial of aripiprazole, subjects must be medication-free for at least 2 weeks prior to baseline. Evidence of hypersensitivity to aripiprazole (defined as an allergic response [e.g., skin rash] or potentially serious adverse effect [e.g., significant tachycardia]). History of neuroleptic malignant syndrome. Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study including being unable to comply with the requirements of the study for any reason.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole<br> | Drug: Aripiprazole<br>* All subjects will initially receive 2.5 mg/day of aripiprazole during the first week. The dosage may be increased to a maximum of 20 mg/day over 8 weeks.<br>* Other names: Abilify;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aberrant Behavior Checklist | The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. The ABC has 5 subscales: Social Withdrawal (16 items) ranging from 0 (not at all) to 48 (severe), Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), and Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe). Items are rated from 0 (not at all) to 3 (severe). | Obtained at Baseline and Week 12 | 
| Clinical Global Impressions- Severity | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. | Obtained at Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Children's Yale-Brown Obsessive Compulsive Scale | The CY-BOCS PDD has been utilized in a largescale clinical treatment study of repetitive behavior in idiopathic ASDs. CYBOCS-PDD scores range from 0 to 20 and measure repetitive/compulsive behavior and not obsessions. Higher score indicate worse outcome. | Obtained at Baseline and Week 12 | 
| Social Responsiveness Scale | The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The score of each individual item is summed to create a total raw score. A total scores results are as follows: 0-62: Within normal limits 63-79: Mild range of impairment 80-108: Moderate range of impairment 109-149: Severe range of impairment | Obtained at Baseline and Week 12 | 
| The Vineland Adaptive Behavior Scales | Vineland Adaptive Behavior Scales are a valid and reliable test to measure a person's adaptive level of functioning. Vineland-II forms aid in diagnosing and classifying intellectual and developmental disabilities and other disorders, such as autism spectrum disorders and developmental delays. The content and scales are organized within a 4 domain structure: Communication, Daily Living, Socialization and Motor Skills. The adaptive behavior composite standard score is computed from the sum of standard scores from the domains and converted into the adaptive behavior composite standard score. Higher scores indicate a higher adaptive level of functioning. | Screen Visit | 
| The Vineland Maladaptive Behavior Subscales | The Vineland Adaptive Behavior Scales include an optional Maladaptive Behavior Index with 27 items. The Maladaptive Behavior Index is a composite of Internalizing, Externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning. The Maladaptive Behavior subscale yields raw scores (0-27). | Week 12 |