Oral Guanabenz for Multiple Sclerosis

NCT02423083 | Terminated Phase 1

• 2 other identifiers: 15011715-N-0117
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Keywords

Neuroprotection; Multiple Sclerosis; Clinical Trial; Safety and Tolerability

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  3.5 months

Secondary Outcomes (1)

• Pharmacokinetics of guanabenz in MS patients

  3.5 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

Drug: Guanabenz

Interventions

Guanabenz DRUG

Treatment arm

Eligibility Criteria

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

You may qualify if:

• MS as defined by the 2010 Revised McDonald MS Diagnostic Criteria (19)
• Age 18-55, inclusive, at the time of the first screening baseline visit
• EDSS 1.0 to 6, inclusive, at the time of the first screening baseline visit
• Able to provide informed consent
• Willing and able to participate in all aspects of trial design and follow-up
• Undergoing treatment with glatiramer acetate for a period of at least 1 year prior to enrollment in the study
• For female patients, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception, including
• birth control pills, injected hormones, and vaginal ring; intrauterine device; barrier methods with spermicide, including diaphragm and condom; or surgical sterilization, including hysterectomy, tubal ligation, and vasectomy) for the duration of the study
• Development of new T2 hyperintense or contrast enhancing lesions by MRI during the screening phase, but 3 such lesions on any single scan

You may not qualify if:

• Alternative diagnoses that better explain neurological disability and MRI findings
• Clinically significant medical condition that, in the best judgment of the investigators, may expose the patient to undue risk of harm or prevent the patient from completing the study (examples include, but are not limited to, cerebrovascular disease, substance abuse, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
• Undergoing treatment with medications that may interact with guanabenz, including anti-hypertensive agents and/or agents leading to increase in catecholamines (such as tricyclic antidepressants and monoamine oxidase inhibitors)
• Medical contraindication to MRI
• Determination, in the best judgment of the investigators, of the need to treat a prospective participant with steroids for management of MS during the screening period
• Pregnant or breastfeeding woman
• Abnormal screening/baseline blood tests exceeding any of the limits defined below:
• A) Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
• B) Total white blood cell count \< 3000/mm3
• C) Platelet count \< 85000/mm3
• D) Serum creatinine level \> 2.0 mg/dl and eGFR (estimated glomerular filtration rate) \< 60
• Evidence of 1 or more clearly documented MS relapses within the last 1 year
• Development of more than 2 lesions per year relative to an MRI performed at least one year before the first screening MRI (the prior MRI can be an outside MRI)
• Development of new T2 hyperintense or contrast-enhancing lesions by MRI during the screening phase

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 19287390 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.

  PMID: 18818381 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.

  PMID: 23554479 BACKGROUND

• 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.

  PMID: 27055915 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Guanabenz

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals

Study Officials

• Irene CM Cortese, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: April 22, 2015
• Study Start: April 21, 2015
• Primary Completion: October 30, 2017
• Study Completion: October 30, 2017
• Last Updated: December 12, 2019

Record last verified: 2017-10-30

Locations

US (1)