Clinical trial NCT03320018: Neuroprotection in Acute Ischemic Stroke
Official title: Pilot Study of the Neuroprotective Effects of Hydrogen and Minocycline in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Stroke, Ischemic
Keywords: neuroprotection
antioxidant
Lead sponsor: Stony Brook University
Sponsor class: OTHER
First posted: 2017-10-24
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

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 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\*

Primary outcomes:
measure: Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq)
timeFrame: 90 days
Secondary outcomes:
measure: Simplified Modified Rankin Scale (sMRSq)
timeFrame: 45 days
measure: NIH Stroke Scale (NIHSS)
timeFrame: 90 days
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
Study officials:
affiliation: Stony Brook University Hospital
name: Dennis Choi, MD, PhD
role: STUDY_DIRECTOR
References: