Back to resultsEvaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge
Primary Purpose
Fragile X Syndrome
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Baclofen
Memantine
Roflumilast
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Fragile X Syndrome
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.
Sites / Locations
- Cincinnati Children's Hospital Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Study Participants
Arm Description
Participants received, in random order, a single dose of placebo, baclofen, roflumilast or memantine with a two-week washout period between doses.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
Clinical Global Impressions-Improvement-Caregiver
The CGI-I requires the caregiver to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
Visual Analog Scale - Caregiver
The parent or caregiver will be asked to assess how much anxiety the participant is expressing on a line between two endpoints (no anxiety to worsened anxiety).
Full Information
NCT ID
NCT05418049
First Posted
May 31, 2022
Last Updated
May 25, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT05418049
Brief Title
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 8, 2022 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
None (Open Label)
Masking Description
Quadruple masking (participant, care provider, investigator and outcomes assessor)
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
All Study Participants
Arm Type
Experimental
Arm Description
Participants received, in random order, a single dose of placebo, baclofen, roflumilast or memantine with a two-week washout period between doses.
Intervention Type
Drug
Intervention Name(s)
Baclofen
Intervention Description
30mg - Supplied as 10mg and 20mg tablets
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
NAMENDA
Intervention Description
two 10 mg tablets
Intervention Type
Drug
Intervention Name(s)
Roflumilast
Other Intervention Name(s)
DAILIRESP
Intervention Description
250 mcg capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo pill
Primary Outcome Measure Information:
Title
Change in EEG Relative Gamma Power
Description
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.
Time Frame
Pre-dose, 3-hour post-dose
Secondary Outcome Measure Information:
Title
Clinical Global Impressions-Improvement
Description
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).
Time Frame
Pre-dose, 3-hour post-dose
Title
Clinical Global Impressions-Improvement-Caregiver
Description
The CGI-I requires the caregiver to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
Time Frame
Pre-dose, 3-hour post-dose
Title
Visual Analog Scale - Caregiver
Description
The parent or caregiver will be asked to assess how much anxiety the participant is expressing on a line between two endpoints (no anxiety to worsened anxiety).
Time Frame
Pre-dose, 3-hour post-dose
Other Pre-specified Outcome Measures:
Title
Probabilistic Reversal Learning (PRL)
Description
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.
Time Frame
Pre-dose, 3-hour post-dose
Title
NIH Cognitive Toolbox
Description
Computerized tasks comprised of 3 subtests where an examinee is shown a series of target stimuli, oral reading components, directional decision-making and picture vocabulary.
Time Frame
3-hour post-dose
Title
Expressive Language Sampling (ELS)
Description
An examinee will provide a sample of their spoken language while they create a narrative of a story. Participants were asked to tell the story of a wordless picture book "Frog Goes to Dinner." First the examiner showed the participant each page of the book at a 10 s interval per page. The examiner then asked the participant to tell the story page by page. The examiner utilized scripted prompts to encourage the participants to narrate the book with his/her own words. Digital audio-recorded samples were then de-identified and transferred to the at the UC Davis MIND Institute for transcription and analysis. The samples were transcribed using Systematic Analysis of Language Transcripts, 2018 Research Version software (SALT). The SALT program performs predetermined and customized analysis of text language files.
Time Frame
3 hour post-dose
Title
Test of Attentional Performance for Children (KiTAP) Test of Alertness
Description
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.
Time Frame
Pre-dose, 3-hour post-dose
Title
Eye-tracking
Description
An examinee will observe a series of pictures and videos on a computer screen where a video will capture gaze preference.
Time Frame
Pre-dose, 3-hour post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hannah J. Sachs, MPA
Phone
513-636-2592
Email
hannah.sachs@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A. Erickson, M.D.
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hannah J. Sachs, MPA
Phone
513-636-2592
Email
hannah.sachs@cchmc.org
First Name & Middle Initial & Last Name & Degree
Craig A. Erickson, M.D.
12. IPD Sharing Statement
Learn more about this trial
Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge
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