Assessing Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy

NCT06065670 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 23-38525
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with acute inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments. No reparative therapies exist for the treatment of acute demyelinating lesions. 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 acute 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 lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination. 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 acute lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination and compare it to the other assessments.

Conditions

Demyelinating Diseases; Demyelination; Corpus Callosum; Multiple Sclerosis Brain Lesion; Multiple Sclerosis Acute and Progressive; Clinically Isolated Syndrome, CNS Demyelinating

Keywords

acute brain lesions; mri; brain; demyelinating lesions; spinal cord

Outcome Measures

Primary Outcomes (9)

• Corpus Callosum Myelin Water Fraction

  The efficacy of clemastine relative to placebo at increasing the myelin water fraction (MWF) (measured in %) from magnetic resonance imaging of the corpus callosum.

  This will be assessed at the baseline visit.

• Change from Baseline in Corpus Callosum Myelin Water Fraction at 3 Months

  The efficacy of clemastine relative to placebo at increasing the myelin water fraction (MWF) (measured in %) from magnetic resonance imaging of the corpus callosum. Change = (3-month % - Baseline %)

  This will be assessed at the baseline and 3 month visits.

• Change from Baseline in Corpus Callosum Myelin Water Fraction at 6 Months

  The efficacy of clemastine relative to placebo at increasing the myelin water fraction (MWF) (measured in %) from magnetic resonance imaging of the corpus callosum. Change = (6-month % - Baseline %)

  This will be assessed at the baseline and 6 month visits.

• Corpus Callosum T1 Relaxation Time

  The efficacy of clemastine relative to placebo at shortening the T1 relaxation time (measured in seconds) within the corpus callosum using T1 mapping protocols in an MRI.

  This will be assessed at the baseline visit.

• Change from Baseline in Corpus Callosum T1 Relaxation Time at 3 Months

  The efficacy of clemastine relative to placebo at shortening the T1 relaxation time (measured in seconds) within the corpus callosum using T1 mapping protocols in an MRI. (3-month time - Baseline time)

  This will be assessed at the baseline and 3-month visits.

• Change from Baseline in Corpus Callosum T1 Relaxation Time at 6 Months

  The efficacy of clemastine relative to placebo at shortening the T1 relaxation time (measured in seconds) within the corpus callosum using T1 mapping protocols in an MRI. (6-month time - Baseline time)

  This will be assessed at the baseline and 6-month visits.

• Corpus Callosum UTE Fraction

  The efficacy of clemastine relative to placebo at increasing the ultrashort echo time (UTE) fraction (measured in %) derived from magnetic resonance imaging of the corpus callosum.

  This will be assessed at the baseline visit.

• Change from Baseline in Corpus Callosum UTE Fraction at 3 Months

  The efficacy of clemastine relative to placebo at increasing the ultrashort echo time (UTE) fraction (measured in %) derived from magnetic resonance imaging of the corpus callosum. Change = (3-month % - Baseline %)

  This will be assessed at the baseline and 3-month visits.

• Change from Baseline in Corpus Callosum UTE Fraction at 6 Months

  The efficacy of clemastine relative to placebo at increasing the ultrashort echo time (UTE) fraction (measured in %) derived from magnetic resonance imaging of the corpus callosum. Change = (6-month % - Baseline %)

  This will be assessed at the baseline and 6-month visits.

Secondary Outcomes (39)

• Optic Radiation Myelin Water Fraction

  This will be assessed at the baseline visit.

• Change from Baseline in Optic Radiation Myelin Water Fraction at 3 Months

  This will be assessed at the baseline and 3-month visits.

• Change from Baseline in Optic Radiation Myelin Water Fraction at 6 Months

  This will be assessed at the baseline and 6-month visits.

• Corticospinal Tract Myelin Water Fraction

  This will be assessed at the baseline visit.

• Change from Baseline in Corticospinal Tract Myelin Water Fraction at 3 Months

  This will be assessed at the baseline and 3-month visits.

Study Arms (2)

Clemastine 12 mg, then clemastine 8 mg, then Placebo

EXPERIMENTAL

Group 1 will receive the treatment (clemastine) for the first 90 days. They will receive clemastine 12 mg for 14 days followed by clemastine 8 mg for 76 days, and then switch to the placebo (a sugar pill) for the remaining 90 days

Drug: Clemastine Fumarate; Drug: Placebo

Placebo, then Clemastine 12 mg, then Clemastine 8 mg

EXPERIMENTAL

Group 1 will receive the placebo for the first 90 days. Then, they will switch to clemastine (treatment) for 90 days. They will receive clemastine 12 mg for 14 days followed by clemastine 8 mg for the remaining 76 days.

Drug: Clemastine Fumarate; Drug: Placebo

Interventions

Placebo DRUG

Matched sugar tablet

Also known as: Sugar pill

Clemastine 12 mg, then clemastine 8 mg, then Placebo; Placebo, then Clemastine 12 mg, then Clemastine 8 mg

Clemastine Fumarate DRUG

12 or 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

Also known as: Clemastine, Dayhist, Dayhist Allergy

Clemastine 12 mg, then clemastine 8 mg, then Placebo; Placebo, then Clemastine 12 mg, then Clemastine 8 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Sandler Neurosciences Building, Neurological Clinical Research Unit

San Francisco, California, 94107, United States

Location

Related Publications (5)

• Mei F, Fancy SPJ, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA, Etxeberria A, Xiao L, Franklin RJM, Green A, Hauser SL, Chan JR. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014 Aug;20(8):954-960. doi: 10.1038/nm.3618. Epub 2014 Jul 6.

  PMID: 24997607 BACKGROUND

• Marques JP, Kober T, Krueger G, van der Zwaag W, Van de Moortele PF, Gruetter R. MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. Neuroimage. 2010 Jan 15;49(2):1271-81. doi: 10.1016/j.neuroimage.2009.10.002. Epub 2009 Oct 9.

  PMID: 19819338 BACKGROUND

• Sheth V, Shao H, Chen J, Vandenberg S, Corey-Bloom J, Bydder GM, Du J. Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies. Neuroimage. 2016 Aug 1;136:37-44. doi: 10.1016/j.neuroimage.2016.05.012. Epub 2016 May 5.

  PMID: 27155128 BACKGROUND

• 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.

  PMID: 29029896 BACKGROUND

• Gagliardo A, Galli F, Grippo A, Amantini A, Martinelli C, Amato MP, Borsini W. Motor evoked potentials in multiple sclerosis patients without walking limitation: amplitude vs. conduction time abnormalities. J Neurol. 2007 Feb;254(2):220-7. doi: 10.1007/s00415-006-0334-5. Epub 2007 Feb 17.

  PMID: 17308868 BACKGROUND

MeSH Terms

Conditions

Demyelinating Diseases; Marchiafava-Bignami Disease

Interventions

Clemastine; Sugars

Condition Hierarchy (Ancestors)

Nervous System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Ari J Green, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harkeerat Halait, BS

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 6-month randomized double-blinded, placebo-controlled, delayed treatment study examining clemastine fumarate as a remyelinating agent in participants with multiple sclerosis. This trial will include n = 44 patients with a confirmed diagnosis of acute demyelinating lesions. Patients who fulfill the enrollment criteria will be randomly assigned (1:1) via block randomization using a random number generator to receive either clemastine for 90 days followed by placebo for 90 days (Clemastine 12 mg for 14 days, clemastine 8 mg for 76 days, then Placebo) or placebo for 90 days followed by clemastine for 90 days (Placebo, then Clemastine 12 mg for 14 days, the clemastine 8 mg for 76 days). If they are on one, patients will be permitted to remain on their standard disease-modifying treatment during the course of the study. These therapies have no identified effect on remyelination.

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 4, 2023
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): October 30, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)