Oral Guanabenz for Multiple Sclerosis

Phase 1

Terminated

• Conditions: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis
• Interventions: Drug: Guanabenz

• Registration Number: NCT02423083
• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

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.

Detailed Description

OBJECTIVE:

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.

STUDY POPULATION:

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.

DESIGN:

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.

OUTCOMES:

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 Timeline

• Study Start: 2015-04-21
• Study First Submitted: 2015-04-21
• Study First Submitted QC: 2015-04-21
• Study First Posted: 2015-04-22
• Status Verified: 2017-10-30
• Primary Completion: 2017-10-30
• Study Completion: 2017-10-30
• Last Update Submitted: 2019-12-11
• Last Update Posted: 2019-12-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Guanabenz	-

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD)	3.5 months

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of guanabenz in MS patients	3.5 months

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States