Acamprosate in Youth With Fragile X Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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Pilot Study of Acamprosate in Youth With Fragile X Syndrome

Conditions
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Fragile X Syndrome, Autism Spectrum Disorders

Intervention / Treatment
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* Drug: Acamprosate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acamprosate<br>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<br> <br> * Other names: Campral;|
| No Intervention: Autism Spectrum Disorder<br>This baseline comparison group will participated in only the psychophysiological and biomarker portion of subject characterization. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acamprosate, Fragile X Syndrome