Clinical trial NCT05418049: Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge
Official title: Evaluating the Neurophysiologic and Clinical Effects of Single-Dose Baclofen, Roflumilast, Memantine, and Placebo in Fragile X Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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: 2022-06-14
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: 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 are placebo, baclofen, roflumilast, and memantine.
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 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.

Primary outcomes:
measure: Change in EEG Relative Gamma Power
timeFrame: Pre-dose, 3-hour post-dose
Secondary outcomes:
measure: Clinical Global Impressions-Improvement
timeFrame: Pre-dose, 3-hour post-dose
measure: Clinical Global Impressions-Improvement-Caregiver
timeFrame: Pre-dose, 3-hour post-dose
measure: Visual Analog Scale - Caregiver
timeFrame: Pre-dose, 3-hour post-dose
Other outcomes:
measure: Probabilistic Reversal Learning (PRL)
timeFrame: Pre-dose, 3-hour post-dose
measure: NIH Cognitive Toolbox
timeFrame: 3-hour post-dose
measure: Expressive Language Sampling (ELS)
timeFrame: 3 hour post-dose
measure: Test of Attentional Performance for Children (KiTAP) Test of Alertness
timeFrame: Pre-dose, 3-hour post-dose
measure: Eye-tracking
timeFrame: Pre-dose, 3-hour post-dose
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: