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

Aripiprazole in Fragile X Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Aripiprazole

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
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Child and Adolescent Psychiatry Clinic - Riley Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole	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 Names: Abilify

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indiana University School of Medicine
• Investigators: Principal Investigator: Craig A. Erickson, MD, Indiana University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 9, 2007
• First Submitted That Met QC Criteria: January 9, 2007
• First Posted (Estimate): January 11, 2007

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 0609-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO