Oral Guanabenz for Multiple Sclerosis
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|ClinicalTrials.gov Identifier: NCT02423083|
Recruitment Status : Terminated
First Posted : April 22, 2015
Last Update Posted : May 16, 2019
- 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.
- To see if guanabenz is safe and well tolerated in people with MS.
- People 18 55 years old with MS who have taken glatiramer acetate for the past year.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis||Drug: Guanabenz||Phase 1|
This Phase 1 clinical study will aim to determine whether therapeutically adequate dosages of guanabenz are safe and well tolerated in patients with multiple sclerosis (MS). It will further provide pharmacokinetic data important for determination of optimal dosing schedule for possible future Phase 2 study.
Six patients, ages between 18-55 inclusive, and diagnosis of definite multiple sclerosis by 2010 Revised McDonald Diagnostic Criteria (Polman et al, 2010) will be enrolled. All patients will have been on treatment with glatiramer acetate, a Food and Drug Administration (FDA) approved disease-modifying therapy, for a minimum of year. Four of the patients will be clinically stable with no clinical relapse in the preceding year and no evidence of active inflammation by MRI during the 2-month screening period; 2 patients will be selected based on evidence of on-going, active inflammation seen by MRI during the screening period.
In this open-label, single site, dose escalation study, the maximum tolerated dose (MTD) of guanabenz in MS patients will be determined. Patients will be screened for participation under the existing MS natural history study 89-N-0045. Sequential patient enrollment will be spaced at least 6 weeks apart. Five study drug doses will be explored: 4mg, 8mg, 16mg, 32mg and 64mg. Dose escalation will ensue if the preceding dose is tolerated, defined both by patient-reported outcomes and objective clinical and imaging assessments. Patients will be maintained on lower doses (4mg-16mg) for 14 days and on higher doses (32 and 64mg) for 28 days.
The primary outcome is MTD, defined as the maximum dose that produces dose-limiting toxicity (DLT) in at most 2 out of the 6 participants. Secondary outcomes include patient-reported outcomes, objective clinical and imaging assessments at 32mg and 64mg, and pharmacokinetics.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Oral Guanabenz for Multiple Sclerosis|
|Study Start Date :||April 21, 2015|
|Actual Primary Completion Date :||October 30, 2017|
|Actual Study Completion Date :||October 30, 2017|
|Experimental: Treatment arm||
- Maximum tolerated dose (MTD) [ Time Frame: 3.5 months ]
- Pharmacokinetics of guanabenz in MS patients [ Time Frame: 3.5 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423083
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Irene CM Cortese, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|