Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge

NCT05418049 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0202U54HD104461
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in EEG Relative Gamma Power

  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.

  Pre-dose, 3-hour post-dose

Secondary Outcomes (3)

• Clinical Global Impressions-Improvement

  Pre-dose, 3-hour post-dose

• Clinical Global Impressions-Improvement-Caregiver

  Pre-dose, 3-hour post-dose

• Visual Analog Scale - Caregiver

  Pre-dose, 3-hour post-dose

Other Outcomes (5)

• Probabilistic Reversal Learning (PRL)

  Pre-dose, 3-hour post-dose

• NIH Cognitive Toolbox

  3-hour post-dose

• Expressive Language Sampling (ELS)

  3 hour post-dose

Study Arms (2)

Experimental Study Participants

EXPERIMENTAL

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

Drug: Baclofen; Drug: Memantine; Drug: Roflumilast

Control Study Participants

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Baclofen DRUG

30mg - Supplied as 10mg and 20mg tablets

Experimental Study Participants

Memantine DRUG

two 10 mg tablets

Also known as: NAMENDA

Experimental Study Participants

Roflumilast DRUG

250 mcg capsule

Also known as: DAILIRESP

Experimental Study Participants

Placebo DRUG

Placebo pill

Control Study Participants

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Baclofen; Memantine; Roflumilast

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Craig A. Erickson, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Quadruple masking (participant, care provider, investigator and outcomes assessor)
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These are placebo, baclofen, roflumilast, and memantine.

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 14, 2022
• Study Start: September 8, 2022
• Primary Completion: October 28, 2025
• Study Completion: March 5, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-11

Locations

US (1)