Clinical trial NCT02998151: Neurophysiological and Acute Pharmacological Studies in FXS Patients
Official title: Neurophysiological and Acute Pharmacological Studies in FXS Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Fragile X Syndrome
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-12-20
Enrollment: 29
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Change in EEG Relative Gamma Power
timeFrame: Pre-dose, 4-hour post-dose
measure: Clinical Global Impressions-Improvement
timeFrame: 4-hour post-dose
Secondary outcomes:
measure: Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
timeFrame: 4-hour post-dose
measure: Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
timeFrame: Pre-dose, 4-hour post dose
measure: Test of Attentional Performance for Children (KiTAP) Test of Alertness
timeFrame: Predose, 4-hour post-dose
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Craig A Erickson, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.