Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge

Cincinnati Children's Hospital Medical Center

Status and phase: Active, not recruiting; Phase 2

Conditions: Fragile X Syndrome

Treatments: Drug: Roflumilast; Drug: Memantine; Drug: Baclofen; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05418049

U54HD104461 (U.S. NIH Grant/Contract)

2022-0202

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: 45 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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45 participants in 2 patient groups, including a placebo group

Experimental Study Participants

Experimental group

Description:

Participants received, in random order, a single dose of placebo, baclofen, roflumilast or memantine with a two-week washout period between doses.

Treatment:

Drug: Baclofen

Drug: Memantine

Drug: Roflumilast

Control Study Participants

Placebo Comparator group

Description:

Participants received, in random order, a single dose of placebo, baclofen, roflumilast or memantine with a two-week washout period between doses.

Treatment:

Drug: Placebo