Back to resultsAcamprosate in Youth With Fragile X Syndrome
Primary Purpose
Fragile X Syndrome, Autism Spectrum Disorders
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acamprosate
Sponsored by
About this trial
This is an interventional treatment trial for Fragile X Syndrome focused on measuring Fragile X Syndrome, Acamprosate
Eligibility Criteria
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.
Sites / Locations
- Riley Child and Adolescent Psychiatry Clinic - Riley Hospital for Children
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Acamprosate
Autism Spectrum Disorder
Arm Description
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.
This baseline comparison group will participated in only the psychophysiological and biomarker portion of subject characterization.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01300923
Brief Title
Acamprosate in Youth With Fragile X Syndrome
Official Title
Pilot Study of Acamprosate in Youth With Fragile X Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome, Autism Spectrum Disorders
Keywords
Fragile X Syndrome, Acamprosate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acamprosate
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Autism Spectrum Disorder
Arm Type
No Intervention
Arm Description
This baseline comparison group will participated in only the psychophysiological and biomarker portion of subject characterization.
Intervention Type
Drug
Intervention Name(s)
Acamprosate
Other Intervention Name(s)
Campral
Primary Outcome Measure Information:
Title
Clinical Global Impression- Severity Scale (CGI-S)
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
Week 10
Secondary Outcome Measure Information:
Title
The Aberrant Behavior Checklist (ABC)
Description
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.
Time Frame
Week 10
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
Week 10
Title
Children's Yale-Brown Obsessive Compulsive Scale Modified for PDD
Description
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.
Time Frame
Week 10
Title
ADHD Rating Scale 4th Edition
Description
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.
Time Frame
Week 10
Title
Vineland Adaptive Behavior Scales-II (VABS-II) Communication Domain
Description
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.
Time Frame
Week 10
Title
Peabody Picture Vocabulary
Description
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.
Time Frame
Week 10
Title
Brain-derived Neurotrophic Factor (BDNF)
Description
BDNF is a protein that supports the survival of existing neurons and growth and differentiation of new neurons and synapses.
Time Frame
Screen and Week 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A. Erickson, M.D.
Organizational Affiliation
Indiana University School of Medicine - Department of Psychiatry
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
Citations:
PubMed Identifier
23436129
Citation
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.
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Acamprosate in Youth With Fragile X Syndrome
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