Oral Guanabenz for Multiple Sclerosis

Summary

Background: \- People with multiple sclerosis (MS) get lesions in their brain and spinal cord. These cause neurological symptoms and sometimes disability. Researchers want to see if a blood pressure drug called guanabenz can repair lesions and help people with MS. Objective: \- To see if guanabenz is safe and well tolerated in people with MS. Eligibility: \- People 18 55 years old with MS who have taken glatiramer acetate for the past year. Design: * Participants will be screened in a separate protocol. For 2 months, they will be examined and have magnetic resonance imaging (MRI) scans. This will decide if they are in the Stable or Active MS study group. * The study will last 5 months. There will be up to 11 visits, 5 overnight. * Visit 1: overnight stay at the clinic: * Medical history and physical exam. * Health questionnaire * Bladder ultrasound scan * Brain MRI * Electrocardiogram (EKG) to measure heart electrical activity * Blood will be drawn through an intravenous (IV) line. * Participants may have tests of strength, muscle tone, and movement. * They will get their first dose of the study drug, a tablet taken once a day. * Participants will take the study drug at home and keep a medicine diary. * The dose will slowly increase. Each time, participants will stay overnight at the clinic. They will have a physical exam, EKG, MRI, and IV blood draw. * Visit 6: Participants will have a physical exam, MRI, and blood drawn. They will get a schedule to slowly lower their drug dose and stop taking guanabenz. * Participants will have 2 final visits. They will have a physical exam, EKG, MRI, and IV blood draw.

Timeline

Start

2015-04-21

Primary completion

2017-10-30

Completion

2017-10-30

Publications

• Background Lin W, Popko B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat Neurosci. 2009 Apr;12(4):379-85. doi: 10.1038/nn.2273. Epub 2009 Mar 15.
• Background Lin W, Kunkler PE, Harding HP, Ron D, Kraig RP, Popko B. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol. 2008 Nov;173(5):1508-17. doi: 10.2353/ajpath.2008.080449. Epub 2008 Sep 25.
• Background Lin W, Lin Y, Li J, Fenstermaker AG, Way SW, Clayton B, Jamison S, Harding HP, Ron D, Popko B. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci. 2013 Apr 3;33(14):5980-91. doi: 10.1523/JNEUROSCI.1636-12.2013.
• Clayton BLL, Popko B. Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia. Brain Res. 2016 Oct 1;1648(Pt B):594-602. doi: 10.1016/j.brainres.2016.03.046. Epub 2016 Apr 4.

Drugs

Indications