Neurophysiological and Acute Pharmacological Studies in FXS Patients

NCT02998151 | Completed Early Phase 1 Results

• 2 other identifiers: CIN001 - {LAM}U54HD082008
• Study Type: interventional
• Target: 29
• 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 (2)

• 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, 4-hour post-dose

• 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).

  4-hour post-dose

Secondary Outcomes (3)

• Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task

  4-hour post-dose

• Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose

  Pre-dose, 4-hour post dose

• Test of Attentional Performance for Children (KiTAP) Test of Alertness

  Predose, 4-hour post-dose

Study Arms (1)

All Study Participants

EXPERIMENTAL

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; Drug: Lovastatin; Drug: Minocycline; Drug: Placebo; Drug: Baclofen

Interventions

Acamprosate DRUG

two 666mg pills

All Study Participants

Lovastatin DRUG

two 20mg pills

All Study Participants

Minocycline DRUG

two 135mg pills

All Study Participants

Placebo DRUG

placebo pill

All Study Participants

Baclofen DRUG

one 30mg pill

All Study Participants

Eligibility Criteria

• Age: 15 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

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

Related Publications (1)

• Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord. 2022 Sep 27;14(1):52. doi: 10.1186/s11689-022-09455-9.

  PMID: 36167501 DERIVED

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Acamprosate; Lovastatin; Minocycline; Baclofen

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)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Tetracyclines; Naphthacenes; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids

Results Point of Contact

• Title: Dr. Craig Erickson
• Organization: Cincinnati Children's Hospital Medical Center

craig.erickson@cchmc.org

513-636-0523

Study Officials

• Craig A Erickson, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, 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 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.

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 20, 2016
• Study Start: January 1, 2016
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 26, 2021
• Results First Posted: November 24, 2021

Record last verified: 2021-11

Locations

US (1)