Acamprosate in Youth With Fragile X Syndrome

Pilot Study of Acamprosate in Youth With Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited form of developmental disability. FXS is inherited from the carrier parent, most often the mothers. FXS is associated with severe interfering behavioral symptoms which include anxiety related symptoms, attention deficit hyperactivity, and aggressive behaviors. Approximately 25-33% of individuals with FXS also meet criteria for autistic disorder. The hypothesis of this study is that treatment with acamprosate will reduce inattention/hyperactivity, language impairment, irritability, social deficits, and cognitive delay in youth with FXS. The purpose of this study is to investigate the effectiveness and tolerability of acamprosate in youth with Fragile X Syndrome and to assess the potential psychophysiological differences between FXS and autism spectrum disorders.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome; Autism Spectrum Disorders
• Intervention / Treatment: Drug: Acamprosate

• Study Type: Interventional
• Enrollment (Actual): 14
• 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: 3 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female outpatients between the ages of 5 and 17 years.
• Confirmed diagnosis of Fragile X Syndrome based upon genetic testing.
• Stable dosing of all psychotropic medications for at least 2 weeks prior to baseline.
• Subjects with a stable seizure disorder or history of only childhood febrile seizures will be included.
• Clinical Global Impression-Severity Score of 4 (Moderately Ill) or greater.
• Must be in good physical health.
• Subjects of child bearing age of both genders will be required to utilize birth control as applicable.

Exclusion Criteria:

• Diagnosis of schizophrenia, another psychotic disorder, bipolar disorder or alcohol or other substance abuse based on Diagnostic and Statistical Manual Fourth Edition-Text Revised (DSM-IV-TR).
• A significant medical condition such as heart, liver, renal or pulmonary disease or unstable seizure disorder.
• Females with a positive urine pregnancy test
• Creatinine clearance of less than 30.
• Concomitant use of another glutamatergic agent (memantine,riluzole, d-cycloserine, amantadine topiramate, gabapentin, among others.
• Evidence of hypersensitivity to acamprosate or potentially serious adverse effect.
• 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acamprosate; The maximum dose of acamprosate to be used in this study is 1998 mg per day for those subjects weighing greater than 60kg and 1332 mg per day for those less weighing less than 60kg.	Drug: Acamprosate; Other Names: Campral
No Intervention: Autism Spectrum Disorder; This baseline comparison group will participated in only the psychophysiological and biomarker portion of subject characterization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression- Severity Scale (CGI-S)	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.	Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Aberrant Behavior Checklist (ABC)	The Aberrant Behavior Checklist (ABC) is a 58-item rating scale used to assess maladaptive behaviors across five original subscales: Irritability (15 items from 0-45), Social Withdrawal (16 items from 0-48), Stereotypy (7 items from 0-21), Hyperactivity (16 items from 0-48), Inappropriate Speech (4 items from 0-12). Additionally, Social Avoidance, a newly developed four-item subscale (from 0-12) of the ABC that captures core social avoidance aspects of Fragile X Syndrome is reported. All items on the ABC are rated from 0 (not at all a problem) to 3 (the problem is severe in degree). Higher scores indicate greater maladaptive behaviors. Differences between Baseline and Week 10 are used as an indicator of change.	Week 10
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	Week 10
Children's Yale-Brown Obsessive Compulsive Scale Modified for PDD	The Children's Yale-Brown Obsessive Compulsive Scales-Modified (CY-BOCS) is a 5-item, semi-structured clinician rating scale modified designed to rate the current severity of repetitive behavior in children and adolescents with PDD. Once the current repetitive behaviors are identified, they are separately rated on 5 items: Time Spent, Interference, Distress, Resistance, and Control. Each of these items is scored on a 5-point scale form 0 (least symptomatic) to 4 (most symptomatic). The CY-BOCS yields a Total Score from 0 to 20 and is sensitive to change.	Week 10
ADHD Rating Scale 4th Edition	The ADHD Rating Scale is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder. The ADHD Rating Scale-IV is completed by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. The total score can range from 0 to 54, with a higher score indicating greater severity.	Week 10
Vineland Adaptive Behavior Scales-II (VABS-II) Communication Domain	The VABS-II is a semi-structured interview designed to assess adaptive functioning in communication, daily living, socialization and motor skills. Recognizing that language is a major area of impairment in the study population, the Communication Domain (99 Items from 0-198), in particular the Expressive Subdomain (54 Items from 0-108) are of interest in this study. Items arranged in a developmental sequence are rated on a 3-point scale. Each item is scored from 0 (never performs the behavior) to 3 (usually performs the behavior independently). Higher scores indicate higher adaptive functioning. Differences between Baseline and Week 10 are used as an indicator of change.	Week 10
Peabody Picture Vocabulary	The Peabody Picture Vocabulary Test is one of the most commonly used assessment tests that measure verbal ability in standard American English vocabulary. This test has been nationally standardized using examinees from various age groups, from children to adults. Thus, the raw scores are equated to mental age, using the norms obtained from standardization. The total standard scores range from 40 (worse receptive vocabulary) to 160 (better receptive vocabulary). The scores can also be converted to percentile rank.	Week 10
Brain-derived Neurotrophic Factor (BDNF)	BDNF is a protein that supports the survival of existing neurons and growth and differentiation of new neurons and synapses.	Screen and Week 10

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Craig A. Erickson, M.D., Indiana University School of Medicine - Department of Psychiatry

Publications and helpful links

General Publications

• Erickson CA, Wink LK, Ray B, Early MC, Stiegelmeyer E, Mathieu-Frasier L, Patrick V, Lahiri DK, McDougle CJ. Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl). 2013 Jul;228(1):75-84. doi: 10.1007/s00213-013-3022-z. Epub 2013 Feb 24.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: August 25, 2010
• First Submitted That Met QC Criteria: February 18, 2011
• First Posted (Estimate): February 23, 2011

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Fragile X Syndrome; Acamprosate
• Additional Relevant MeSH Terms: Mental Disorders; 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; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Autism Spectrum Disorder; Fragile X Syndrome; Alcohol Deterrents; Acamprosate
• Other Study ID Numbers: 1003-26