H2M: Neuroprotection in Acute Ischemic Stroke
Study Details
Study Description
Brief Summary
This is a pilot randomized control trial (RCT) to explore the possible beneficial effect of a novel combination therapy consisting of molecular hydrogen H2 plus minocycline ("H2M"), on neurological recovery after acute ischemic stroke.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
This will be a pilot trial exploring the ability of a novel combination ("H2M") of molecular hydrogen (an antioxidant) and minocycline (a widely used antibiotic known to inhibit the activation of matrix metallo-proteinase-9 and poly(ADP-ribose) polymerase), to protect brain tissue from ischemia/reperfusion injury that occurs during and after an ischemic stroke. Both hydrogen and minocycline have excellent safety profiles, have been previously demonstrated individually to reduce infarction in animal models of stroke, and have potentially synergistic mechanisms of action against ischemic brain damage. The mechanisms of action of both agents would be specifically relevant to patients receiving tissue plasminogen activator (tPA) or thrombectomy, and achieving some degree of therapeutic reperfusion.
This will be a double blinded, placebo-controlled trial. Eligible and willing subjects will be randomly assigned to be treated with either H2M or placebo, in addition to standard treatments. The treatment with H2M or placebo will start as soon as possible after diagnosis of stroke, and continue for three days (hydrogen) and five days (minocycline) respectively. Measures of stroke severity and disability will be recorded at baseline, and through a follow-up phone call (45 days) and clinic visit (90 days).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hydrogen/Minocycline Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days. Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days. |
Drug: Hydrogen
Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Other Names:
Drug: Minocycline
Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
Other Names:
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| Placebo Comparator: Placebo Hydrogen/Placebo Minocycline Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline. |
Other: Placebo Hydrogen
Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Other: Placebo Minocycline
Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
Outcome Measures
Primary Outcome Measures
- simplified modified Rankin Scale (sMRSq) [90 days]
rating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead).
Secondary Outcome Measures
- simplified modified Rankin Scale (sMRSq) [45 days]
rating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead).
- NIH Stroke Scale (NIHSS) [90 days]
15-item neurologic examination scale for severity of stroke. Ratings for each item are scored with 3 to 5 grades. A total NIHSS of 0 is normal; 1-4 is considered a minor stroke; 5-15 moderate; 16-20 moderate to severe; and 21-42 severe.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged 18 years old or over
-
Presenting to/at Stony Brook University Hospital with acute ischemic stroke
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Baseline (at admission to study) National Institute of Health Stroke Scale (NIHSS) of ≥ 5
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Administration of study medication possible within 24 hours of last known well
Exclusion Criteria:
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Pre-existing neurological disability (historical NIHSS > 3); unable to live independently 3. Severe stroke or comorbidities likely to result in patient dying within 3 months 4. Acute or chronic renal failure with calculated creatinine clearance < 30 5. Liver disease leading to > 3x elevation in liver transaminases or significant loss of synthetic capacity* 6. Thrombocytopenia (<100x10^9platelets / L blood) 7. Pre-existing infectious disease requiring antibiotic therapy that have a negative interaction with minocycline. (Penicillin, amoxicillin, ampicillin, bacampicillin, carbenicillin, cloxacillin, dicloxacillin, methicillin, mezlocillin, nafcillin, oxacillin, piperacillin, ticarcillin)
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Pregnancy or nursing. Females of reproductive age will be required to use barrier contraception or abstain from sexual intercourse while on study medications, as minocycline may render oral contraceptives less effective.
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Known allergy to tetracycline group of drugs 10. Concurrent treatment with retinoids or ergot alkaloids 11. Inability to safely tolerate the fluid load (iv normal saline or po water) associated with study medication* 12. Treatment with another investigational drug within the last 30 days that may interfere with this study's medications* 13. Inability to tolerate or comply with study procedures*
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stony Brook University Hospital | Stony Brook | New York | United States | 11794-8121 |
Sponsors and Collaborators
- Stony Brook University
- Korea Institute of Science and Technology
Investigators
- Study Director: Dennis Choi, MD, PhD, Stony Brook University Hospital
- Principal Investigator: Adrian Marchidann, MD, Stony Brook University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 932805