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Neurophysiological and Acute Pharmacological Studies in FXS Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02998151
Recruitment Status : Completed
First Posted : December 20, 2016
Results First Posted : November 24, 2021
Last Update Posted : November 26, 2021
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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.

Condition or disease Intervention/treatment Phase
Fragile X Syndrome Drug: Acamprosate Drug: Lovastatin Drug: Minocycline Drug: Placebo Drug: Baclofen Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Neurophysiological and Acute Pharmacological Studies in FXS Patients
Study Start Date : January 2016
Actual Primary Completion Date : November 2020
Actual Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: All Study Participants
Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Drug: Acamprosate
two 666mg pills

Drug: Lovastatin
two 20mg pills

Drug: Minocycline
two 135mg pills

Drug: Placebo
placebo pill

Drug: Baclofen
one 30mg pill




Primary Outcome Measures :
  1. Change in EEG Relative Gamma Power [ Time Frame: Pre-dose, 4-hour post-dose ]
    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.

  2. Clinical Global Impressions-Improvement [ Time Frame: 4-hour post-dose ]
    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).


Secondary Outcome Measures :
  1. Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task [ Time Frame: 4-hour post-dose ]
    Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).

  2. Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose [ Time Frame: Pre-dose, 4-hour post dose ]
    Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.

  3. Test of Attentional Performance for Children (KiTAP) Test of Alertness [ Time Frame: Predose, 4-hour post-dose ]
    Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.



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Ages Eligible for Study:   15 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). 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.

Exclusion Criteria:

  • Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline 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 central nervous system neurological disease unrelated to FXS.
  • Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and benzodiazepines and are exclusions (within 5 half-lives). Those taking other psychiatric medications must be on stable doses for 4 weeks before any testing.
  • For female subjects of child bearing potential, a positive urine pregnancy test.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02998151


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Craig A Erickson, M.D. Children's Hospital Medical Center, Cincinnati
  Study Documents (Full-Text)
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02998151    
Other Study ID Numbers: CIN001 - {LAM}
U54HD082008 ( U.S. NIH Grant/Contract )
First Posted: December 20, 2016    Key Record Dates
Results First Posted: November 24, 2021
Last Update Posted: November 26, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fragile X Syndrome
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Minocycline
Acamprosate
Baclofen
Lovastatin
L 647318
Dihydromevinolin
Anti-Bacterial Agents
Anti-Infective Agents
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticholesteremic Agents