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| ID | Type | Description | Link |
|---|---|---|---|
| U54HD082008 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acamprosate | Drug | two 666mg pills |
| |
| Lovastatin |
| 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, 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Craig A Erickson, M.D. | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36167501 | Derived | 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. |
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Participants engaged in a baseline visit to gather preliminary data and ensure study compliance. Participants were then randomly assigned to different sequences for receiving acamprosate, lovastatin, minocycline, baclofen, and placebo. There was a 2-week washout period between visits.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Study Participants | 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 arm was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Missing 1 placebo, 1 lovastatin who contributed data with excessive movement or other artifact, or were unable to complete the task. | Posted | Mean | Standard Deviation | percent of power in gamma frequencies | Pre-dose, 4-hour post-dose |
|
Adverse events were collected up to four weeks after the final dosing visit.
Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: placebo pill | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | CTCAE v5.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Craig Erickson | Cincinnati Children's Hospital Medical Center | 513-636-0523 | craig.erickson@cchmc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Latest study protocol with baclofen | Aug 27, 2019 | Jan 26, 2021 | Prot_SAP_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Previous study protocol with original arms | Dec 1, 2015 | Jan 26, 2021 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Latest consent form with baclofen | Aug 30, 2019 | Jan 26, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D005600 | Fragile X Syndrome |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D000077443 | Acamprosate |
| D008148 | Lovastatin |
| D008911 | Minocycline |
| D001418 | Baclofen |
| ID | Term |
|---|---|
| D013654 | Taurine |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
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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.
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| Drug |
two 20mg pills |
|
| Minocycline | Drug | two 135mg pills |
|
| Placebo | Drug | placebo pill |
|
| Baclofen | Drug | one 30mg pill |
|
| 4-hour post-dose |
| Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours 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. | Pre-dose, 4-hour post dose |
| Test of Attentional Performance for Children (KiTAP) Test of Alertness | 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. | Predose, 4-hour post-dose |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task | Measure Description: 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). | One participant did not complete the Woodcock Johnson. | Mean | Standard Deviation | scores on a scale |
|
| OG001 |
| Acamprosate |
Acamprosate: two 666mg pills |
| OG002 | Lovastatin | Lovastatin: two 20mg pills |
| OG003 | Minocycline | Minocycline: two 135mg pills |
| OG004 | Baclofen | Baclofen: one 30mg pill |
|
|
| Primary | 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). | CGI-I was not collected for one participant on their minocycline day and another participant on their baclofen day. | Posted | Mean | Standard Deviation | score on a scale | 4-hour post-dose |
|
|
|
| Secondary | Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task | 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). | Data is missing from 2 placebo, 1 acamprosate, 1 lovastatin, 2 minocycline, and 1 baclofen. | Posted | Mean | Standard Deviation | score on a scale | 4-hour post-dose |
|
|
|
| Secondary | Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours 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. | One participant is missing from placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to repeat list words back to experimenter (nonverbal). Baclofen and placebo are each additionally missing one participant who did not complete the pre-dose or post-dose task. | Posted | Mean | Standard Deviation | number of words remembered | Pre-dose, 4-hour post dose |
|
|
|
| Secondary | Test of Attentional Performance for Children (KiTAP) Test of Alertness | 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. | One participant is missing from the placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to participate in the task. An additional one participant each is missing from placebo, acamprosate, and lovastatin conditions due to uncollected data at either the pre-dose or post-dose timepoint. | Posted | Mean | Standard Deviation | change in median RT in milliseconds | Predose, 4-hour post-dose |
|
|
|
| 27 |
| 0 |
| 27 |
| 3 |
| 27 |
| EG001 | Acamprosate | Acamprosate: two 666mg pills | 0 | 16 | 0 | 16 | 7 | 16 |
| EG002 | Lovastatin | Lovastatin: two 20mg pills | 0 | 29 | 0 | 29 | 4 | 29 |
| EG003 | Minocycline | Minocycline: two 135mg pills | 0 | 27 | 0 | 27 | 4 | 27 |
| EG004 | Baclofen | Baclofen: one 30mg pill | 0 | 18 | 0 | 18 | 4 | 18 |
| Stomach pain | Gastrointestinal disorders | CTCAE v5.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE v5.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | CTCAE v5.0 | Systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE v5.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v5.0 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | CTCAE v5.0 | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE v5.0 | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE v5.0 | Systematic Assessment |
|
| Mania | Psychiatric disorders | CTCAE v5.0 | Systematic Assessment | excessive talking or hyperactivity |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE v5.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE v5.0 | Systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D025064 | Sex Chromosome Disorders |
| D025063 | Chromosome Disorders |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D040181 | Genetic Diseases, X-Linked |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |