Recruiting
Phase 1
Phase 2

Clemastine Fumarate

Sponsor:

UCLA

Code:

NCT05359653

Conditions

Multiple Sclerosis (MS)

Multiple Sclerosis, Relapsing-Remitting

Multiple Sclerosis, Primary Progressive

Multiple Sclerosis, Chronic Progressive

Multiple Sclerosis Relapse

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Clemastine Fumarate

Placebo

Study Details

Brief summary:

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with chronic inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments.

No reparative therapies exist for the treatment of multiple sclerosis. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at the University of California, San Francisco (UCSF). Following in vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of multiple sclerosis in the context of chronic optic neuropathy. That pilot study was recently completed and is the first randomized control trial documenting efficacy for a putative remyelinating agent for the treatment of MS. The preselected primary efficacy endpoint (visual evoked potential) was met and a strong trend to benefit was seen for the principal secondary endpoint assessing function (low contrast visual acuity). That trial number was 13-11577.

This study seeks to follow up on that study and examine clemastine fumarate's protective and reparative effects in the context of chronic demyelinating brain lesions as imaged by multi-parametric MRI assessments. The investigators will be assessing the effects of clemastine fumarate as a remyelinating therapy and assessing its effect on MRI metrics of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis.

In addition to using conventional multi-parametric MRI assessments, this study will also evaluate a new MRI technique called Ultrashort Echo Time (UTE) MRI to assess the effects of clemastine fumarate as a remyelinating therapy of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis and compare it to the other assessments.

Conditions

Multiple Sclerosis (MS)

Multiple Sclerosis, Relapsing-Remitting

Multiple Sclerosis, Primary Progressive

Multiple Sclerosis, Chronic Progressive

Multiple Sclerosis Relapse

Study ID

NCT05359653

Start date

Aug 1, 2023

Status verified date

Jun, 2026

Completion date

Jun 1, 2027

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Written informed consent must be obtained prior to any assessment being performed.
  • Patients diagnosed with relapsing remitting multiple sclerosis and a disease duration of < 15 years
  • Male or female patients aged 18-55 years (inclusive)
  • Use of appropriate contraception during period of trial (women). Before entry women must be:

  • Post-menopausal for at least 1 year OR
  • Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, male partner vasectomy or otherwise incapable of pregnancy) OR
  • Practicing a highly effective method of birth control if sexually active, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g., condoms, diaphragm or cervical cap with spermicidal foam, cream or gel), or male partner sterilization consistent with local regulations regarding use of birth control methods for patients participating in clinical trials, for the duration of their participation in the study OR
  • Not heterosexually active (patients who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study) OR
  • Practicing true abstinence (when this is in line with the preferred and usual lifestyle of the subject) Period abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) is not an acceptable method.

Exclusion Criteria:

  • Radiologic identification of marked brain atrophy relative to patients age based on recent MRI and interpretation of expert neuroradiologist or PI
  • New lesion in most recent MRI (within 3 months)
  • Hypersensitivity to clemastine or other arylalkylamine antihistamines, or any of the excipients.
  • Treatment with corticosteroids within 30 days prior to screening.
  • Expanded Disability Status Scale (EDSS) ≥ 4.5
  • History of significant cardiac conduction block.
  • History of cancer.
  • Suicidal ideation or behavior in 6 months prior to baseline.
  • Pregnancy, breastfeeding or planning to become pregnant.
  • Involved with other study protocols simultaneously without prior approval.
  • Concomitant use of any other putative remyelinating therapy as determined by the investigator.
  • 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 transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase > 2 times the upper limit of normal. (Reported within 72 hours)
  • History of drug or alcohol abuse within the past year.
  • Untreated 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, allergic, renal, or other major diseases that in the PI's judgment may affect the 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
  • Inability to participate in MRI, including extreme claustrophobia.
  • Any dental braces or permanent or undetachable metals in the jaw or face.

Study Design

Enrollment

74 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Clemastine 8 mg, then Placebo

Group 1 will receive the treatment (clemastine 8mg/day) for the first 90 days and then switch to the placebo (a sugar pill) for the remaining 90 days

experimental: Placebo, then Clemastine 8 mg

Group 2 will receive the placebo (a sugar pill) for the first 90 days and then switch to the treatment (clemastine 8mg/day) for the remaining 90 days

Interventions

Clemastine Fumarate

8 mg Clemastine tablet. Clemastine fumarate was approved by the Food and Drug Administration (FDA) for the treatment of allergic rhinitis (seasonal allergies) in 1977 and was approved for over-the-counter marketing in 1992. Clemastine is not FDA approved as a remyelinating therapy

Placebo

Matched sugar tablet

Primary outcome measure

  • Corpus Callosum Myelin Water Fraction [ Time Frame: This will be assessed at the baseline visit. ]
  • Change from Baseline in Corpus Callosum Myelin Water Fraction at 3 Months [ Time Frame: This will be assessed at the baseline and 3-month visits. ]
  • Change from Baseline in Corpus Callosum Myelin Water Fraction at 6 Months [ Time Frame: This will be assessed at the baseline and 6-month visits. ]
  • Corpus Callosum T1 Relaxation Time [ Time Frame: This will be assessed at the baseline visit. ]
  • Change from Baseline in Corpus Callosum T1 Relaxation Time at 3 Months [ Time Frame: This will be assessed at the baseline and 3-month visits. ]
  • Change from Baseline in Corpus Callosum T1 Relaxation Time at 6 Months [ Time Frame: This will be assessed at the baseline and 6-month visits. ]
  • Corpus Callosum UTE Fraction [ Time Frame: This will be assessed at the baseline visit. ]
  • Change from Baseline in Corpus Callosum UTE Fraction at 3 Months [ Time Frame: This will be assessed at the baseline and 3-month visits. ]
  • Change from Baseline in Corpus Callosum UTE Fraction at 6 Months [ Time Frame: This will be assessed at the baseline and 6-month visits. ]

Central Contacts and Locations

Central contacts

Harkeerat Halait, BS

415-745-1304Harkeerat.Halait@ucsf.edu

Angelica Montevirgen

415-745-1304Angelica.Montevirgen@ucsf.edu

Locations

Sandler Neurosciences Building, Neurological Clinical Research Unit

Recruiting

San Francisco, California, United States, 94107

Contacts

Harkeerat Halait, BS

415-745-1304Harkeerat.Halait@ucsf.edu

Angelica Montevirgen, BS

415-745-1304Angelica.Montevirgen@ucsf.edu

Principal Investigator:

Ari J Green, MD

More Information

Sponsor

University of California, San Francisco

Last update posted

Jul 2, 2026

Last verified

Jun, 2026

Keywords

  • multiple sclerosis
  • mri
  • brain
  • spinal cord

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, San Francisco on 2026-07-02.