Multiple Sclerosis, Relapsing-RemittingPhase 2ReBUILDNCT02040298
Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis
A Phase 2 study testing Clemastine in people with Multiple Sclerosis, Relapsing-Remitting, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Clemastine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria
- Age 18-60.
- Latency delay > 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)
- Retinal nerve fiber layer (RNFL) > 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)
- No optic neuritis in prior 6 months
- Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening
Show all 9Show fewer
- Use of appropriate contraception during period of trial (females of child bearing potential)
- Understand and sign informed consent.
- Expanded disability status scale (EDSS) 0-6.0 (inclusive)
Who cannot join
- Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).
- Myopia > -7 Diopters (Severe myopia)
- History of significant cardiac conduction block
- History of cancer
- Known optic neuritis in involved eye > 5 years ago OR disease duration > 15 years
- Suicidal ideation or behaviour in 6 months prior to screening
Show all 17Show fewer
- Pregnancy, breastfeeding, or planning to become pregnant.
- Involved with other study protocol simultaneously without prior approval. 9. Concomitant use of Dalfampridine (4AP or diamino4AP) or any other formulation of 4AP or diamino4AP.
- Concomitant use of any other putative remyelinating therapy as determined by investigator.
- Treatment with corticosteroids within 30 days prior to screening
- Prior treatment with total lymphoid irradiation, T cell or T cell receptor vaccination
- Prior treatment with alemtuzumab, mitoxantrone, or cyclophosphamide
- Serum creatinine > 1.5 mg/dL; aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2 times the upper limit of normal
- History of drug or alcohol abuse within the past year
- Untreated vitamin B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism
- Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, psychiatric allergic, renal or other major diseases that in the PI's judgment may affect interpretation of study results or patient safety.
- History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Multiple Sclerosis Center
San Francisco, California, 94518
About this study
Official title: A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis
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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Clemastine, Placebo
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClemastineDrug
Also called Clemastine Fumarate,, Tavist -1
4mg tablet twice daily
PlaceboDrug
Placebo tablet twice daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Clemastine; Drug: Placebo |
| 3 months Placebo , 2 months Clemastine | Active comparator | Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months. Receives: Drug: Clemastine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Treatment start to treatment end, up to 3 months.
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Start of treatment to end of treatment, up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionSep 2015
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ari J. Green, MD, MCR, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02040298
- Sponsor's protocol ID
- ReBUILD
- Acronym
- ReBUILD
- Status last verified
- Sep 2025
- First submitted
- 10 Jan 2014
- Last updated
- 17 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 10467384Green 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.
PubMed 29029896Abdelhak 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.
PubMed 35710320
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT02040298
- Acronym / sponsor ID
- ReBUILD / ReBUILD
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 20 Jan 2014 (estimated)
- Results
- Posted 15 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 3 months Clemastine, 2 months Placebo | Active comparator | Drug: Clemastine, Drug: Placebo4mg 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 | Drug: Clemastine, Drug: PlaceboPlacebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria
- Age 18-60.
- Latency delay > 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)
- Retinal nerve fiber layer (RNFL) > 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)
- No optic neuritis in prior 6 months
Key exclusion criteria (17 listed)
- Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).
- Myopia > -7 Diopters (Severe myopia)
- History of significant cardiac conduction block
- History of cancer
- Known optic neuritis in involved eye > 5 years ago OR disease duration > 15 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClemastineAlso: Clemastine Fumarate,, Tavist -14mg tablet twice daily | Drug | 3 months Clemastine, 2 months Placebo, 3 months Placebo , 2 months Clemastine |
| PlaceboPlacebo tablet twice daily | Drug | 3 months Clemastine, 2 months Placebo, 3 months Placebo , 2 months Clemastine |
Primary outcome
Full Field Visual Evoked Potential (VEP)
Time frame: Treatment start to treatment end, up to 3 months.
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.
3 secondary outcomes
Tolerability of Clemastine in Multiple Sclerosis (MS) Patients
Time frame: Treatment start to treatment end, up to 3 months.
Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR)
Time frame: Treatment start to treatment end, up to 3 months.
Expanded Disability Status Scale (EDSS) Score
Time frame: Start of treatment to end of treatment, up to 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10467384Fischer 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.
- Results publication: PubMed 29029896Green 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.
- Derived from this study: PubMed 35710320Abdelhak 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.
- ReBUILD trial description University of California, San Francisco Multiple Sclerosis CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ari J. Green, MD, MCR principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clemastine in people with Multiple Sclerosis, Relapsing-Remitting, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Full Field Visual Evoked Potential (VEP) (time frame: Treatment start to treatment end, up to 3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02040298, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.