Evaluating the Neurophysiologic and Clinical Effects of S... | NCT05418049

NCT05418049

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
U54HD104461	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	NIH

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Baclofen	Drug	30mg - Supplied as 10mg and 20mg tablets	Experimental Study Participants

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Clinical Global Impressions-Improvement	The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).	Pre-dose, 3-hour post-dose
Clinical Global Impressions-Improvement-Caregiver

Other Outcomes

Measure	Description	Time Frame
Probabilistic Reversal Learning (PRL)	An examinee will be prompted to complete four different reversal learning tasks on a computer, each which had two phases: Acquisition and Reversal. Participants will be instructed to choose one of two identical stimuli positioned in different locations on the screen. Participant behavior will be reinforced on 80% of correct responses and on 20% of incorrect responses. During the acquisition phase, participants chose one of two stimulus locations until they identified the correct location on 8 of 10 consecutive trials. Then, they proceeded to the reversal phase in which the correct location is switched without warning, and participants had to identify the new correct location on 8 of 10 consecutive trials. Testing was discontinued if they did not reach criterion within 50 trials on either phase. Participants completed two practice tests to establish test comprehension. We computed total number of trials to reach criterion and number of errors after reversal.

Eligibility Module

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.

ID	Term
D038901	X-Linked Intellectual Disability
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic