Multiple Sclerosis, Neuropathic Pain
Conditions
Brief summary
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.
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.
Interventions
DRUGglibenclamide
oral extended release pill
DRUGPlacebo
Placebo
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
In stage 2, medication will be either placebo or treatment, blinded in appearance. Investigators will not be aware of placebo/treatment assignment.
Intervention model 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| blood glucose | 10 hours | blood glucose during 10 hour pharmacokinetic measurements |
| tmax | 10 hours | time to maximum concentration |
| t 1/2 | 10 hours | time to 1/2 maximum concentration |
| Cmax | over 10 hours | maximum concentration |
| Safety | Through week 13 | Full reporting of any adverse events on study drug |
| Cmin | Over 10 hours | Minimum concentration |
| AUC | 10 hours | Area under curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the PROMISE Pain Interference Score | Through week 13 | 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. |
| Change in PROMIS Neuropathic Pain Scale Score | Through week 13 | 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. |
Countries
United States
Contacts
Primary ContactKerry Naunton
Backup ContactDaniel Harrison
Outcome results
None listed