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

Primary Purpose

Demyelinating Diseases, Demyelination; Corpus Callosum, Multiple Sclerosis Brain Lesion

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Clemastine Fumarate
Placebo
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Demyelinating Diseases focused on measuring acute brain lesions, mri, brain, demyelinating lesions, spinal cord

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sandler Neurosciences Building, Neurological Clinical Research Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Clemastine 12 mg, then clemastine 8 mg, then Placebo

Placebo, then Clemastine 12 mg, then Clemastine 8 mg

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.
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 %)
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 %)
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.
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)
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)
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.
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 %)
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 %)

Secondary Outcome Measures

Optic Radiation Myelin Water Fraction
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation.
Change from Baseline in Optic Radiation Myelin Water Fraction at 3 Months
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation. Change = (3-month % - Baseline %)
Change from Baseline in Optic Radiation Myelin Water Fraction at 6 Months
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation. Change = (6-month % - Baseline %)
Corticospinal Tract Myelin Water Fraction
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract.
Change from Baseline in Corticospinal Tract Myelin Water Fraction at 3 Months
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract. (3-month % - Baseline %)
Change from Baseline in Corticospinal Tract Myelin Water Fraction at 6 Months
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract. (6-month % - Baseline %)
Optic Radiation T1 Relaxation time
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation.
Change from Baseline in Optic Radiation T1 Relaxation time at 3 Months
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation. (3-month time - Baseline time)
Change from Baseline in Optic Radiation T1 Relaxation time at 6 Months
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation. (6-month time - Baseline time)
Corticospinal Tract T1 Relaxation Time
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract.
Change from Baseline in Corticospinal Tract T1 Relaxation Time at 3 Months
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract. (3-month time - Baseline time)
Change from Baseline in Corticospinal Tract T1 Relaxation Time at 6 Months
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract. (6-month time - Baseline time)
Optic radiation UTE Fraction
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation.
Change from Baseline in Optic radiation UTE Fraction at 3 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation. Change = (3-month % - Baseline %)
Change from Baseline in Optic radiation UTE Fraction at 6 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation. Change = (6-month % - Baseline %)
Corticospinal Tract UTE Fraction
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract.
Change from Baseline in Corticospinal Tract UTE Fraction at 3 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract. (3-month % - Baseline %)
Change from Baseline in Corticospinal Tract UTE Fraction at 6 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract. (6-month % - Baseline %)
Lesion of interest (LOI) MWF
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Change from Baseline in Lesion of interest (LOI) MWF at 3 Months
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month % - Baseline %)
Change from Baseline in Lesion of interest (LOI) MWF at 6 Months
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month % - Baseline %)
LOI T1 Relaxation Time
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Change from Baseline in LOI T1 Relaxation Time at 3 Months
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month time - Baseline time)
Change from Baseline in LOI T1 Relaxation Time at 6 Months
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month time - Baseline time)
LOI UTE Fraction
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Change from Baseline in LOI UTE Fraction at 3 Months
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month % - Baseline %)
Change from Baseline in LOI UTE Fraction at 6 Months
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month % - Baseline %)
Whole Brain MWF
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Change from Baseline in Whole Brain MWF at 3 Months
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (3-month % - Baseline %)
Change from Baseline in Whole Brain MWF at 6 Months
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (6-month % - Baseline %)
Whole Brain T1 Relaxation Time
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Change from Baseline in Whole Brain T1 Relaxation Time at 3 Months
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. (3-month time - Baseline time)
Change from Baseline in Whole Brain T1 Relaxation Time at 6 Months
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. (6-month time - Baseline time)
Whole Brain UTE Fraction
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Change from Baseline in Whole Brain UTE Fraction at 3 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (3-month % - Baseline %)
Change from Baseline in Whole Brain UTE Fraction at 6 Months
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (6-month % - Baseline %)
Clemastine Tolerability
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC).
Change from Baseline in Clemastine Tolerability at 3 Months
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Change = (3-month tolerability - Baseline tolerability)
Change from Baseline in Clemastine Tolerability at 6 Months
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Change = (6-month tolerability - Baseline tolerability)

Full Information

First Posted
September 19, 2023
Last Updated
October 3, 2023
Sponsor
University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT06065670
Brief Title
Assessing Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy
Acronym
ReINFORCE
Official Title
A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Treatments capable of remyelination are a major unmet need for demyelinating diseases that involve myelin damage, loss, or dysfunction in the central nervous system (CNS). Acute demyelination of axons is believed to be injurious to neurons and serves as a major contributor to irreversible cell loss that underlies permanent disability. Available treatments are primarily immunosuppressing, without directly addressing or fully preventing axonal degeneration and disability. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at UCSF. The screen demonstrated that clemastine promoted the differentiation of the endogenous oligodendrocyte precursor cells (OPCs) into mature myelinating oligodendrocytes. Following in vivo validation, an FDA investigational new drug (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 clinical trial is intended to assess magnetic resonance imaging evidence of remyelination using Clemastine Fumarate in patients with acute demyelinated lesions. Specifically speaking, the primary objective will assess various multi-parametric MRI sequences on the corpus callosum region, a region that animal models studies identified as a promising candidate for assessing remyelination. The aim was to help define the potential for MRI in measuring remyelination in acute lesions, determine the optimal sequences and location for measuring myelin recovery, and help guide trial design for future remyelinating trials. Finally, the study is designed to assess tolerability and clinical efficacy of Clemastine using outcomes intended to assess for (a) adverse events and (b) recovery of myelin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Clemastine 12 mg, then clemastine 8 mg, then Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo, then Clemastine 12 mg, then Clemastine 8 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Clemastine Fumarate
Other Intervention Name(s)
Clemastine, Dayhist, Dayhist Allergy
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Matched sugar tablet
Primary Outcome Measure Information:
Title
Corpus Callosum Myelin Water Fraction
Description
The efficacy of clemastine relative to placebo at increasing the myelin water fraction (MWF) (measured in %) from magnetic resonance imaging of the corpus callosum.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corpus Callosum Myelin Water Fraction at 3 Months
Description
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 %)
Time Frame
This will be assessed at the baseline and 3 month visits.
Title
Change from Baseline in Corpus Callosum Myelin Water Fraction at 6 Months
Description
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 %)
Time Frame
This will be assessed at the baseline and 6 month visits.
Title
Corpus Callosum T1 Relaxation Time
Description
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.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corpus Callosum T1 Relaxation Time at 3 Months
Description
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)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Corpus Callosum T1 Relaxation Time at 6 Months
Description
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)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Corpus Callosum UTE Fraction
Description
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.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corpus Callosum UTE Fraction at 3 Months
Description
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 %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Corpus Callosum UTE Fraction at 6 Months
Description
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 %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Secondary Outcome Measure Information:
Title
Optic Radiation Myelin Water Fraction
Description
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Optic Radiation Myelin Water Fraction at 3 Months
Description
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Optic Radiation Myelin Water Fraction at 6 Months
Description
The efficacy of Clemastine relative to placebo at increasing the MWF (measured in %) of the optic radiation. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Corticospinal Tract Myelin Water Fraction
Description
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corticospinal Tract Myelin Water Fraction at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract. (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Corticospinal Tract Myelin Water Fraction at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing the MWF (measured in %) of the corticospinal tract. (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Optic Radiation T1 Relaxation time
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Optic Radiation T1 Relaxation time at 3 Months
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation. (3-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Optic Radiation T1 Relaxation time at 6 Months
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the optic radiation. (6-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Corticospinal Tract T1 Relaxation Time
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corticospinal Tract T1 Relaxation Time at 3 Months
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract. (3-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Corticospinal Tract T1 Relaxation Time at 6 Months
Description
To evaluate the efficacy of Clemastine relative to placebo at increasing the T1 relaxation time (measured in seconds) of the corticospinal tract. (6-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Optic radiation UTE Fraction
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Optic radiation UTE Fraction at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Optic radiation UTE Fraction at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the optic radiation. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Corticospinal Tract UTE Fraction
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Corticospinal Tract UTE Fraction at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract. (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Corticospinal Tract UTE Fraction at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) of the corticospinal tract. (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Lesion of interest (LOI) MWF
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Lesion of interest (LOI) MWF at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Lesion of interest (LOI) MWF at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
LOI T1 Relaxation Time
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in LOI T1 Relaxation Time at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in LOI T1 Relaxation Time at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
LOI UTE Fraction
Description
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in LOI UTE Fraction at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in LOI UTE Fraction at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing UTE fraction (measured in %) of the lesion(s) of interest, stratified based on enhancement status on prior MRIs. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Whole Brain MWF
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Whole Brain MWF at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Whole Brain MWF at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing MWF (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Whole Brain T1 Relaxation Time
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Whole Brain T1 Relaxation Time at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. (3-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Whole Brain T1 Relaxation Time at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing T1 relaxation time (measured in seconds) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. (6-month time - Baseline time)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Whole Brain UTE Fraction
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter.
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Whole Brain UTE Fraction at 3 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (3-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Whole Brain UTE Fraction at 6 Months
Description
The efficacy of clemastine relative to placebo at increasing the UTE fraction (measured in %) across the whole-brain divided into regions of normal-appearing white matter (NAWM), cortical gray matter, and deep gray matter. Change = (6-month % - Baseline %)
Time Frame
This will be assessed at the baseline and 6-month visits.
Title
Clemastine Tolerability
Description
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC).
Time Frame
This will be assessed at the baseline visit.
Title
Change from Baseline in Clemastine Tolerability at 3 Months
Description
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Change = (3-month tolerability - Baseline tolerability)
Time Frame
This will be assessed at the baseline and 3-month visits.
Title
Change from Baseline in Clemastine Tolerability at 6 Months
Description
The tolerability of Clemastine in this population. This will include a special focus with regards to fatigue as this is a major symptom for patients suffering from demyelinating lesions using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Change = (6-month tolerability - Baseline tolerability)
Time Frame
This will be assessed at the baseline and 6-month visits.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Makenna Chapman, BS
Phone
415-745-1304
Email
Makenna.Chapman@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ari J Green, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sandler Neurosciences Building, Neurological Clinical Research Unit
City
San Francisco
State/Province
California
ZIP/Postal Code
94107
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Makenna Chapman, BS
Phone
415-745-1304
Email
Makenna.Chapman@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Ari J Green, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24997607
Citation
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.
Results Reference
background
PubMed Identifier
19819338
Citation
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.
Results Reference
background
PubMed Identifier
27155128
Citation
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.
Results Reference
background
PubMed Identifier
29029896
Citation
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.
Results Reference
background
PubMed Identifier
17308868
Citation
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.
Results Reference
background

Learn more about this trial

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

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