Back to resultsNeurophysiological and Acute Pharmacological Studies in FXS Patients
Primary Purpose
Fragile X Syndrome
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Acamprosate
Lovastatin
Minocycline
Placebo
Baclofen
Sponsored by
About this trial
This is an interventional basic science trial for Fragile X Syndrome
Eligibility Criteria
Inclusion Criteria:
- Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). FXS is defined as full FMR1 mutations (>200 CGG repeats) confirmed by genetic testing.
- General good health as determined by physical exam, medical history and laboratory work up.
Exclusion Criteria:
- Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline will be excluded.
- Subjects will also be excluded if they have taken any investigational drug within 3 months, have a history of substance abuse or dependence within 6 months, or significant psychiatric or central nervous system neurological disease unrelated to FXS.
- Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and benzodiazepines and are exclusions (within 5 half-lives). Those taking other psychiatric medications must be on stable doses for 4 weeks before any testing.
- For female subjects of child bearing potential, a positive urine pregnancy test.
- Potential subjects with a creatinine clearance < 50 mL/min will be excluded.
- Identified medical issues, inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.
Sites / Locations
- Cincinnati Children's Hospital Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Study Participants
Arm Description
Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Outcomes
Primary Outcome Measures
Change in EEG Relative Gamma Power
EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.
Clinical Global Impressions-Improvement
The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
Secondary Outcome Measures
Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).
Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.
Test of Attentional Performance for Children (KiTAP) Test of Alertness
Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.
Full Information
NCT ID
NCT02998151
First Posted
December 1, 2016
Last Updated
November 23, 2021
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT02998151
Brief Title
Neurophysiological and Acute Pharmacological Studies in FXS Patients
Official Title
Neurophysiological and Acute Pharmacological Studies in FXS Patients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
November 2020 (Actual)
Study Completion Date
November 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to utilize neurophysiologic assessments, behavioral measures and clinical measures to assess how much deficits associated with Fragile X Syndrome from pre-dose to post-dose using pharmacology.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Model Description
This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All Study Participants
Arm Type
Experimental
Arm Description
Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Intervention Type
Drug
Intervention Name(s)
Acamprosate
Intervention Description
two 666mg pills
Intervention Type
Drug
Intervention Name(s)
Lovastatin
Intervention Description
two 20mg pills
Intervention Type
Drug
Intervention Name(s)
Minocycline
Intervention Description
two 135mg pills
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo pill
Intervention Type
Drug
Intervention Name(s)
Baclofen
Intervention Description
one 30mg pill
Primary Outcome Measure Information:
Title
Change in EEG Relative Gamma Power
Description
EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.
Time Frame
Pre-dose, 4-hour post-dose
Title
Clinical Global Impressions-Improvement
Description
The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
Time Frame
4-hour post-dose
Secondary Outcome Measure Information:
Title
Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
Description
Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).
Time Frame
4-hour post-dose
Title
Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
Description
Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.
Time Frame
Pre-dose, 4-hour post dose
Title
Test of Attentional Performance for Children (KiTAP) Test of Alertness
Description
Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.
Time Frame
Predose, 4-hour post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). FXS is defined as full FMR1 mutations (>200 CGG repeats) confirmed by genetic testing.
General good health as determined by physical exam, medical history and laboratory work up.
Exclusion Criteria:
Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline will be excluded.
Subjects will also be excluded if they have taken any investigational drug within 3 months, have a history of substance abuse or dependence within 6 months, or significant psychiatric or central nervous system neurological disease unrelated to FXS.
Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and benzodiazepines and are exclusions (within 5 half-lives). Those taking other psychiatric medications must be on stable doses for 4 weeks before any testing.
For female subjects of child bearing potential, a positive urine pregnancy test.
Potential subjects with a creatinine clearance < 50 mL/min will be excluded.
Identified medical issues, inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A Erickson, M.D.
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36167501
Citation
Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord. 2022 Sep 27;14(1):52. doi: 10.1186/s11689-022-09455-9.
Results Reference
derived
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Neurophysiological and Acute Pharmacological Studies in FXS Patients
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