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The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis. The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with multiple sclerosis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. The study will also assess the robustness and stability of this clinical effect in patients taking clemastine for up to 3 months. Patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 3 months Clemastine, 2 months Placebo | Active Comparator | 4mg clemastine twice daily for first 3 months -- crossover -- equivalent quantity/frequency of placebo for last 2 months |
|
| 3 months Placebo , 2 months Clemastine | Active Comparator | Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clemastine | Drug | 4mg tablet twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Full Field Visual Evoked Potential (VEP) | The primary objective is to evaluate the efficacy of Clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials.Visual evoked potentials (VEP) are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain. VEP latencies were collected at Baseline, Month 1, Month 3, and Month 5. | Treatment start to treatment end, up to 3 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Tolerability of Clemastine in Multiple Sclerosis (MS) Patients | Will demonstrate the tolerability of Clemastine in this population. This will include special focus with regards to fatigue as this is a major symptom for patients suffering from multiple sclerosis.This will be assessed by administering a fatigue questionnaire called the Multidimensional Assessment of Fatigue (MAF) at all four visits throughout the study. MAF scale range is 0-50. Lower scores indicate lower levels of fatigue and higher scores indicate higher levels of fatigue. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Creatinine Level | Blood sample will be collected at each visit to evaluate health status... | Baseline, 1 month, 3 month, 5 month |
| Serum Triglyceride Level | Blood sample will be collected at each visit to evaluate health status. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ari J. Green, MD, MCR | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Multiple Sclerosis Center | San Francisco | California | 94518 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10467384 | Background | Fischer JS, LaRocca NG, Miller DM, Ritvo PG, Andrews H, Paty D. Recent developments in the assessment of quality of life in multiple sclerosis (MS). Mult Scler. 1999 Aug;5(4):251-9. doi: 10.1177/135245859900500410. | |
| 29029896 | Result | Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Budingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017 Dec 2;390(10111):2481-2489. doi: 10.1016/S0140-6736(17)32346-2. Epub 2017 Oct 10. |
| Label | URL |
|---|---|
| ReBUILD trial description University of California, San Francisco Multiple Sclerosis Center | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Clemastine First, Then Placebo | Participants first received Clemastine 4mg twice daily for 3 months. Then they received Placebo (matching Clemastine 4mg) twice daily for 2 months. |
| FG001 | Placebo First, Then Clemastine | Participants first received Placebo (matching Clemastine 4mg) twice daily for 3 months. Then they received Clemastine 4mg twice daily for 2 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (3 Months) |
| |||||||||||||
| Second Intervention (2 Months) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Clemastine First, Then Placebo | Participants first received Clemastine 4mg tablet twice daily for 3 months, then they received Placebo (matching Clemastine 4mg) for 2 months. |
| BG001 | Placebo First, Then Clemastine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Full Field Visual Evoked Potential (VEP) | The primary objective is to evaluate the efficacy of Clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials.Visual evoked potentials (VEP) are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain. VEP latencies were collected at Baseline, Month 1, Month 3, and Month 5. | The data for 7 eyes did not meet criteria for inclusion in analysis (i.e., absent or unidentifiable waveforms.). | Posted | Mean | Standard Deviation | ms | Treatment start to treatment end, up to 3 months. | eyes | eyes |
|
Through study completion, an average of 5 months.
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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 | Clemastine | Participants received Clemastine 4mg twice daily for either 3 months or 2 months. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased trigylcerides | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tracy Tran, BA | UCSF | 415-353-2707 | tracy.tran@ucsf.edu |
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| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D002974 | Clemastine |
| ID | Term |
|---|---|
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo tablet twice daily |
|
| Treatment start to treatment end, up to 3 months. |
| Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR) | To evaluate the efficacy of Clemastine relative to placebo in increasing magnetization transfer ratios derived from magnetic resonance imaging (MRI) of the brain during the period of exposure to active treatment. To evaluate the efficacy of Clemastine relative to placebo at reducing radial diffusivity derived from diffusion tensor imaging as assessed by magnetic resonance imaging (MRI) during the period of exposure to active medication. | Treatment start to treatment end, up to 3 months. |
| Expanded Disability Status Scale (EDSS) Score | To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 90 days compared to placebo (Group A) & at 150 days compared to day 90 (Group B). EDSS is an ordinal scale for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) & an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. The FSs are the Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, & Cerebral functions. FSs & EDSS steps assessed in a standardized manner. EDSS is a widely used &accepted instrument to evaluate disability status at a given time & longitudinally, to assess disability progression in clinical studies in MS. | Start of treatment to end of treatment, up to 3 months |
| Baseline, 1 month, 3 month, 5 month |
| Vitamin B-12 Level | Blood sample will be collected at each visit to evaluate health status. | Baseline, 1 month, 3 month, 5 month |
| Human Chorionic Gonadotropin (hCG) Level in Female Patients of Childbearing Potential | Blood and urine sample will be collected to assess pregnancy status of all female participants of child bearing potential. | Baseline, 1 month, 3 month, 5 month |
| 35710320 | Derived | Abdelhak A, Cordano C, Boscardin WJ, Caverzasi E, Kuhle J, Chan B, Gelfand JM, Yiu HH, Oertel FC, Beaudry-Richard A, Condor Montes S, Oksenberg JR, Lario Lago A, Boxer A, Rojas-Martinez JC, Elahi FM, Chan JR, Green AJ. Plasma neurofilament light chain levels suggest neuroaxonal stability following therapeutic remyelination in people with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 Jun 16:jnnp-2022-329221. doi: 10.1136/jnnp-2022-329221. Online ahead of print. |
| NOT COMPLETED |
|
Participants first received Placebo (matching Clemastine 4mg) tablet twice daily for 3 months, then they received Clemastine 4mg twice daily for 2 months.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Disease duration | Mean | Standard Deviation | years |
|
| EDSS | Expanded Disability Status Scale (EDSS) is an ordinal scale for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) and an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. | Mean | Standard Deviation | units on a scale |
|
| History of optic neuritis | Count of Participants | Participants |
|
| Time since optic neuritis | Mean | Standard Deviation | years |
|
| VEP P100 latency | Visual Evoked Potential (VEP); prominent positive deflection (P100) | Mean | Standard Deviation | milliseconds |
|
| OCT Retinal Nerve Fiber Layer (RNFL) | Optical Coherence Tomography (OCT) Retinal Nerve Fiber Layer (RNFL) | Mean | Standard Deviation | µm |
|
| OCT Macular volume | Mean | Standard Deviation | mm^3 |
|
| LCLA | Low Contrast Letter Acuity (LCLA) is scored from 0-70. Higher scores are better. | Mean | Standard Deviation | Number of letters read correctly |
|
| SDMT | Symbol Digit Modalities Test (SDMT) is scored 0-110. Higher scores are better. | Mean | Standard Deviation | number of correct substitutions |
|
| MAF | Mean | Standard Deviation | units on a scale |
|
| 6-min walk | Mean | Standard Deviation | feet |
|
| 25-foot walk | Mean | Standard Deviation | seconds |
|
| Myelin water fraction | Mean | Standard Deviation | ratio |
|
| MTR 25 | Mean | Standard Deviation | ratio |
|
| FA white matter | Mean | Standard Deviation | ratio |
|
| OG001 |
| Placebo |
Participants who received Placebo tablet (matching clemastine 4mg) twice daily in either the first 3 months or last 2 months of the study. |
|
|
| Secondary | Tolerability of Clemastine in Multiple Sclerosis (MS) Patients | Will demonstrate the tolerability of Clemastine in this population. This will include special focus with regards to fatigue as this is a major symptom for patients suffering from multiple sclerosis.This will be assessed by administering a fatigue questionnaire called the Multidimensional Assessment of Fatigue (MAF) at all four visits throughout the study. MAF scale range is 0-50. Lower scores indicate lower levels of fatigue and higher scores indicate higher levels of fatigue. | Posted | Mean | Standard Deviation | score on a scale | Treatment start to treatment end, up to 3 months. |
|
|
|
| Secondary | Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR) | To evaluate the efficacy of Clemastine relative to placebo in increasing magnetization transfer ratios derived from magnetic resonance imaging (MRI) of the brain during the period of exposure to active treatment. To evaluate the efficacy of Clemastine relative to placebo at reducing radial diffusivity derived from diffusion tensor imaging as assessed by magnetic resonance imaging (MRI) during the period of exposure to active medication. | MRI done at baseline, month 3, month 5 | Posted | Mean | Standard Deviation | Ratio | Treatment start to treatment end, up to 3 months. |
|
|
|
| Secondary | Expanded Disability Status Scale (EDSS) Score | To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 90 days compared to placebo (Group A) & at 150 days compared to day 90 (Group B). EDSS is an ordinal scale for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) & an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. The FSs are the Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, & Cerebral functions. FSs & EDSS steps assessed in a standardized manner. EDSS is a widely used &accepted instrument to evaluate disability status at a given time & longitudinally, to assess disability progression in clinical studies in MS. | Posted | Mean | Standard Deviation | score on a scale | Start of treatment to end of treatment, up to 3 months |
|
|
|
| Other Pre-specified | Serum Creatinine Level | Blood sample will be collected at each visit to evaluate health status... | Not Posted | Baseline, 1 month, 3 month, 5 month | Participants |
| Other Pre-specified | Serum Triglyceride Level | Blood sample will be collected at each visit to evaluate health status. | Not Posted | Baseline, 1 month, 3 month, 5 month | Participants |
| Other Pre-specified | Vitamin B-12 Level | Blood sample will be collected at each visit to evaluate health status. | Not Posted | Baseline, 1 month, 3 month, 5 month | Participants |
| Other Pre-specified | Human Chorionic Gonadotropin (hCG) Level in Female Patients of Childbearing Potential | Blood and urine sample will be collected to assess pregnancy status of all female participants of child bearing potential. | Not Posted | Baseline, 1 month, 3 month, 5 month | Participants |
| 0 |
| 50 |
| 0 |
| 50 |
| 10 |
| 50 |
| EG001 | Placebo | Participants received Placebo (matching Clemastine 4mg) for either 3 months or 2 months. | 0 | 50 | 0 | 50 | 15 | 50 |
| Severe fatigue | Investigations | Systematic Assessment |
|
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| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| MWF 50 at baseline |
|
| MTR 25: full brain change from baseline |
|
| MTR: white matter change from baseline |
|
| MWF 50 change from baseline |
|