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

• ClinicalTrials.gov Identifier: NCT00420459
• Recruitment Status: Completed
• First Posted: January 11, 2007
• Results First Posted: April 18, 2017
• Last Update Posted: April 18, 2017
• Sponsor: Indiana University School of Medicine
• Information provided by (Responsible Party): Indiana University ( Indiana University School of Medicine )

Tracking Information

• First Submitted Date: January 9, 2007
• First Posted Date: January 11, 2007
• Results First Submitted Date: July 29, 2015
• Results First Posted Date: April 18, 2017
• Last Update Posted Date: April 18, 2017
• Study Start Date: April 2007
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2017)

• Aberrant Behavior Checklist [ Time Frame: Obtained at Baseline and Week 12 ]
  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 [ Time Frame: Obtained at Baseline and Week 12 ]
  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.

Original Primary Outcome Measures (submitted: January 9, 2007)

• Parent-rated irritability subscale of Aberrant Behavior Checklist (ABC)
• Clinician-rated Clinical Global Impression (CGI)- global improvement item (CGI-I)

Current Secondary Outcome Measures (submitted: March 29, 2017)

• The Children's Yale-Brown Obsessive Compulsive Scale [ Time Frame: Obtained at Baseline and Week 12 ]
  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 [ Time Frame: Obtained at Baseline and Week 12 ]
  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 [ Time Frame: Screen Visit ]
  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 [ Time Frame: Week 12 ]
  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).

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome
• Official Title: Aripiprazole in Fragile X Syndrome
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fragile X Syndrome

Intervention

Drug: Aripiprazole

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.

Other Name: Abilify

Study Arms

Experimental: Aripiprazole

Intervention: Drug: Aripiprazole

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 9, 2007): 12
• Original Enrollment: Same as current
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males and females between the ages of 5 and 35 years and
2. Body weight greater than or equal to 15 kg
3. Confirmed diagnosis of Fragile X Syndrome based upon genetic testing results.
4. Outpatients.
5. 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.
6. Clinical Global Impression Scale Severity score (CGI-S) of at greater than or equal to 4 (Moderately Ill)
7. A score of at greater than or equal to 18 on the Irritability subscale of the Aberrant Behavior Checklist (ABC) at screen and baseline.
8. Mental age of greater than or equal to 18 months as measured by the Wechsler, revised Leiter, or Mullen tests
9. 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:

1. DSM-IV diagnosis of schizophrenia, another psychotic disorder, bipolar disorder or alcohol or other substance abuse within the last 6 months.
2. 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.
3. Subjects with an unstable seizure disorder will be excluded.
4. Females with a positive urine pregnancy test.
5. 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.
6. Evidence of hypersensitivity to aripiprazole (defined as an allergic response [e.g., skin rash] or potentially serious adverse effect [e.g., significant tachycardia]).
7. History of neuroleptic malignant syndrome.
8. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 35 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00420459
• Other Study ID Numbers: 0609-22
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Indiana University ( Indiana University School of Medicine )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Indiana University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Craig A. Erickson, MD; Indiana University

• PRS Account: Indiana University
• Verification Date: March 2017