Back to resultsA Prospective Open-label Study of Aripiprazole in Fragile X Syndrome
Primary Purpose
Fragile X Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aripiprazole
Sponsored by
About this trial
This is an interventional treatment trial for Fragile X Syndrome
Eligibility Criteria
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.
Sites / Locations
- Riley Child and Adolescent Psychiatry Clinic - Riley Hospital for Children
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aripiprazole
Arm Description
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
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.
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
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.
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).
Full Information
NCT ID
NCT00420459
First Posted
January 9, 2007
Last Updated
March 29, 2017
Sponsor
Indiana University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT00420459
Brief Title
A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome
Official Title
Aripiprazole in Fragile X Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University School of Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aripiprazole
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
Abilify
Intervention Description
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.
Primary Outcome Measure Information:
Title
Aberrant Behavior Checklist
Description
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).
Time Frame
Obtained at Baseline and Week 12
Title
Clinical Global Impressions- Severity
Description
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.
Time Frame
Obtained at Baseline and Week 12
Secondary Outcome Measure Information:
Title
The Children's Yale-Brown Obsessive Compulsive Scale
Description
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.
Time Frame
Obtained at Baseline and Week 12
Title
Social Responsiveness Scale
Description
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
Time Frame
Obtained at Baseline and Week 12
Title
The Vineland Adaptive Behavior Scales
Description
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.
Time Frame
Screen Visit
Title
The Vineland Maladaptive Behavior Subscales
Description
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).
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A. Erickson, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Riley Child and Adolescent Psychiatry Clinic - Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21318565
Citation
Erickson CA, Stigler KA, Wink LK, Mullett JE, Kohn A, Posey DJ, McDougle CJ. A prospective open-label study of aripiprazole in fragile X syndrome. Psychopharmacology (Berl). 2011 Jul;216(1):85-90. doi: 10.1007/s00213-011-2194-7. Epub 2011 Feb 12.
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A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome
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