Neurophysiological and Acute Pharmacological Studies in FXS Patients
Overview
- Phase
- Early Phase 1
- Intervention
- Acamprosate
- Conditions
- Fragile X Syndrome
- Sponsor
- Children's Hospital Medical Center, Cincinnati
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Change in EEG Relative Gamma Power
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
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.
Arms & Interventions
All Study Participants
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: Acamprosate
All Study Participants
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: Lovastatin
All Study Participants
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: Minocycline
All Study Participants
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: Placebo
All Study Participants
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: Baclofen
Outcomes
Primary Outcomes
Change in EEG Relative Gamma Power
Time Frame: Pre-dose, 4-hour post-dose
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
Time Frame: 4-hour post-dose
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 Outcomes
- Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task(4-hour post-dose)
- Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose(Pre-dose, 4-hour post dose)
- Test of Attentional Performance for Children (KiTAP) Test of Alertness(Predose, 4-hour post-dose)