A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in MS Patients Taking Clemastine Fumarate as a Myelin Repair Therapy
University of California, San Francisco
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.
Description
Treatments capable of remyelination are a major unmet need for multiple sclerosis and other diseases that involve myelin damage, loss, or dysfunction in the central nervous system (CNS). Chronic 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 MS 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…
Eligibility
- Age range
- 18–55 years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- DrugClemastine 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
- DrugPlacebo
Matched sugar tablet
Location
- Sandler Neurosciences Building, Neurological Clinical Research UnitSan Francisco, California