OER Glibenclamide for Neuropathic Pain in Multiple Sclerosis

A Pilot Study of the Pharmacodynamics and Clinical Effects of Oral Extended Release (OER) Glibenclamide in Multiple Sclerosis Patients With Neuropathic Pain

This is an early phase safety evaluation of the use of oral extended release (OER) glibenclamide, which is otherwise known as glyburide, for use as a treatment for neurologic pain in people with multiple sclerosis. Patients will receive medication to assess safety and tolerability.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Neuropathic Pain
• Intervention / Treatment: Drug: Placebo; Drug: glibenclamide

Detailed Description

This is a 2-stage pilot study of the pharmacodynamics and clinical effects of OER glibenclamide in MS patients with neuropathic pain. This pilot study will include 10 subjects. In Stage 1 of the study, which will last 5 days, unblinded subjects will take test-drug twice daily each day and participate in PK determinations. Successful completion of this Stage will establish the ability of a subject to safely tolerate the test-drug. In Stage 2 of the Study, which will last 3 months, blinded subjects who have demonstrated the ability to safely tolerate the test-drug will be asked to evaluate its clinical efficacy specifically with regard to neuropathic pain. By using a 3-block/on-off design with blinding, each subject will serve as their own control during the Stage-2 efficacy part of the study.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kerry Naunton; Phone Number: 410 328 1885; Email: knaunton@som.umaryland.edu
• Study Contact Backup: Name: Daniel Harrison; Phone Number: 410-328-5605; Email: dharrison@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-65
2. Diagnosis of multiple sclerosis per the 2017 Revised McDonald Criteria
3. Score of ≥ 19 on the painDETECT questionnaire

Exclusion Criteria:

1. Severe renal disorder from the patient's history (e.g., dialysis) or eGFR of < 30 ml/min.1.73m2
2. Severe liver disease, or ALT > 3 times upper limit of normal or bilirubin >2 times normal
3. Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or QTc > 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention within the past 3 months
4. T2DM treated with insulin or oral medication
5. Blood glucose < 55 mg/dL at enrollment or immediately prior to administration of study drug or a clinically significant history of hypoglycemia.
6. Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); glibornuride (Glutril)
7. Known allergy to sulfa or specific allergy to sulfonylurea drugs
8. Known G6PD enzyme deficiency
9. Pregnancy. Women must be either postmenopausal, permanently sterilized or, if ≤50 years old must have a negative test for pregnancy obtained before enrollment
10. Breast-feeding women who do not agree to stop breastfeeding during Study Drug infusion and for 7 days following the end of Study Drug infusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral extended release glibenclamide; Stage 1, Pharmacokinetics/Pharmacodynamics: This will be a 5 day, unblinded evaluation while participants receive OER-glibenclamide; Stage 2, Safety/Efficacy: This part of the study occurs during weeks 2-13, in 3 successive blocks of 4 weeks each. During this stage, group assignments are randomized, and subjects are blinded as to test-drug vs. placebo. Depending on group assignment, exposure to test-drug may occur early (week-2) or later (week-6). In both groups, exposure to placebo occurs for 4 weeks and exposure to drug occurs for 8 successive weeks.	Drug: glibenclamide; oral extended release pill; Other Names: glyburide
Placebo Comparator: Placebo; 2. Stage 2, Safety/Efficacy: This part of the study occurs during weeks 2-13, in 3 successive blocks of 4 weeks each. During this stage, group assignments are randomized, and subjects are blinded as to test-drug vs. placebo. Depending on group assignment, exposure to test-drug may occur early (week-2) or later (week-6). In both groups, exposure to placebo occurs for 4 weeks and exposure to drug occurs for 8 successive weeks.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum concentration	over 10 hours
Safety	Full reporting of any adverse events on study drug	Through week 13
Cmin	Minimum concentration	Over 10 hours
AUC	Area under curve	10 hours
tmax	time to maximum concentration	10 hours
t 1/2	time to 1/2 maximum concentration	10 hours
blood glucose	blood glucose during 10 hour pharmacokinetic measurements	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PROMIS Neuropathic Pain Scale Score	The questionnaire uses a standard T-score metric, with a mean of 50 and a standard deviation of 10 for a relevant reference population (often the US general population). Higher scores indicate a greater level of neuropathic pain qualities.	Through week 13
Change in the PROMISE Pain Interference Score	The PROMIS Pain Interference (PROMIS-PI) scale is a patient-reported outcome measure that assesses how pain affects daily life, including physical, mental, and social activities, as well as sleep and enjoyment. Scores are typically presented on a T-score metric, where 50 is the U.S. general population mean, with higher scores indicating greater pain interference.	Through week 13

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Daniel M Harrison, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: October 17, 2025
• First Submitted That Met QC Criteria: October 27, 2025
• First Posted (Estimated): October 28, 2025

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Sclerosis; Neuralgia; Sulfur Compounds; Organic Chemicals; Amides; Sulfones; Urea; Sulfonylurea Compounds; Glyburide
• Other Study ID Numbers: HP-00115908

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No