Neurophysiological and Acute Pharmacological Studies in FXS Patients

Cincinnati Children's Hospital Medical Center

Status and phase: Completed; Early Phase 1

Conditions: Fragile X Syndrome

Treatments: Drug: Minocycline; Drug: Acamprosate; Drug: Baclofen; Drug: Placebo; Drug: Lovastatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02998151

U54HD082008 (U.S. NIH Grant/Contract)

CIN001 - {LAM}

Details and patient eligibility

About

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.

Enrollment: 29 patients

Sex: All

Ages: 15 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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29 participants in 1 patient group

All Study Participants

Experimental group

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.

Treatment:

Drug: Acamprosate

Drug: Minocycline

Drug: Lovastatin

Drug: Placebo

Drug: Baclofen