Neuroprotection in Acute Ischemic Stroke

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).

Inclusion Criteria:

1. Aged 18 years old or over

2. Presenting to/at SBUH with acute ischemic stroke

3. Baseline (at admission to study) National Institute of Health Stroke Scale (NIHSS)
between 5-22 inclusive

4. Administration of study medication possible within 24 hours of last known well -

Exclusion Criteria:

1. Other major diseases of the central nervous system, including brain tumors,
Alzheimer's disease, Parkinson's disease, demyelinating disease, inflammatory brain or
vascular disease, craniotomy, traumatic encephalopathy, or idiopathic intracranial
hypertension*

2. Pre-existing neurological disability (historical NIHSS > 0); 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 > 2x elevation in liver transaminases or significant loss of
synthetic capacity*

6. Thrombocytopenia (<100x109platelets / L blood)

7. Pre-existing infectious disease requiring antibiotic therapy

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.

9. Known allergy to tetracycline group of drugs

10. Concurrent treatment with retinoids or ergot alkaloids

11. Inability to safely tolerate the fluid load (iv NS 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*