Neuroprotection in Acute Ischemic Stroke (H2M)

Stony Brook University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Stroke, Ischemic

Treatments: Other: Placebo Minocycline; Drug: Minocycline; Other: Placebo Hydrogen; Drug: Hydrogen

Study type: Interventional

Funder types: Other

Identifiers

NCT03320018

932805

Details and patient eligibility

About

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.

Full 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).

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18 years old or over
2. Presenting to/at Stony Brook University Hospital with acute ischemic stroke
3. Baseline (at admission to study) National Institute of Health Stroke Scale (NIHSS) of ≥ 5
4. Administration of study medication possible within 24 hours of last known well

Exclusion criteria

1. 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) 8. 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.

2. 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*

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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15 participants in 2 patient groups, including a placebo group

Hydrogen/Minocycline

Experimental group

Description:

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.

Treatment:

Drug: Hydrogen

Drug: Minocycline

Placebo Hydrogen/Placebo Minocycline

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo Hydrogen

Other: Placebo Minocycline