Evaluating the effects of a single dose drug challenge on Fragile X Syndrome

Evaluating the Neurophysiologic and Clinical Effects of Single-Dose Baclofen, Roflumilast, Memantine, and Placebo in Fragile X Syndrome

This study is testing if a single dose of different medications can help improve symptoms in adults with Fragile X Syndrome.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: Children's Hospital Medical Center, Cincinnati (other)
• Locations: 1 site (Cincinnati, Ohio)
• Trial ID: NCT05418049 on ClinicalTrials.gov

What this trial studies

This study aims to assess the neurophysiologic and clinical effects of a single dose of pharmacological agents in individuals with Fragile X Syndrome (FXS). Participants aged 18-45 who have completed a prior study will receive either baclofen, memantine, roflumilast, or a placebo. The study will measure changes in deficits associated with FXS through neurophysiologic assessments and behavioral measures before and after drug administration. The goal is to better understand the impact of these medications on individuals with FXS.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-45 with a confirmed diagnosis of Fragile X Syndrome and stable mental health.

Not a fit: Patients with a history of intolerance to the study medications or significant psychiatric conditions unrelated to FXS may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for individuals with Fragile X Syndrome.

How similar studies have performed: Other studies have explored pharmacological interventions for Fragile X Syndrome, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

* Subjects ages 18-45, with FXS who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome" (IRB # 2015-8425) or appropriate baseline measures through Biorepository (2013-7327).
* 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.
* Stanford Binet IQ \<85
* Stable dosing of psychotropic drugs for at least 4 weeks.

Exclusion Criteria:

* Subjects with a history of intolerance to baclofen, roflumilast, or memantine 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 CNS neurological disease unrelated to FXS.
* Uncontrolled seizures or history of epilepsy with a seizure in the past 6 months
* Auditory or visual impairments that cannot be corrected based on visual and auditory screener benchmarks.
* Moderate to severe renal or hepatic impairment and determined by a study physician incorporating data from exam, medical history and laboratory value evaluation among other data points.
* Use of barbiturates, benzodiazepines, antiepileptics, or other GABAergic or glutamatergic modulators
* Current use of: Amifampridine, Butalbital, Codeine, Doxylamine, Ethanol, Hydrocodone, Isocarboxazid, Kava, Metoclopramide, Midazolam, Oxybate, Phenelzine, Promethazine, Thalidomide, Tranylcypromine, Trimethobenzamide, Erythromycin, Ketoconazole, Fluvoxamine, Enoxacin, and Cimetidine.
* Those taking other psychiatric medications must be on stable doses for 4 weeks before the baseline visit.
* Pregnancy or breast-feeding. For female subjects of child bearing potential, a urine pregnancy test will be performed.
* 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.

Where this trial is running

Cincinnati, Ohio

• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Craig A. Erickson, M.D. — Children's Hospital Medical Center, Cincinnati
• Study coordinator: Hannah J. Sachs, MPA

Conditions: Fragile X Syndrome