Neuroprotection in Acute Ischemic Stroke

NCT03320018 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 932805
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke, Ischemic

Keywords

neuroprotection; antioxidant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq)

  rating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead). mRS scores at 90 days will be classified as favorable or unfavorable based on the baseline NIHSS measured at time of enrollment. Subjects in the lowest baseline severity tertile (NIHSS 5-7) will need to have a 90 day mRS score of 0 to be considered to have a favorable outcome. Subjects with baseline NIHSS 8-14 will need a 90 day mRS score 0-1 to be considered to have a favorable outcome; those with baseline NIHSS 15-25 will need a 90 day mRS score 0-2 to be considered to have a favorable outcome.

  90 days

Secondary Outcomes (2)

• Simplified Modified Rankin Scale (sMRSq)

  45 days

• NIH Stroke Scale (NIHSS)

  90 days

Study Arms (2)

Hydrogen/Minocycline

EXPERIMENTAL

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; Drug: Minocycline

Placebo Hydrogen/Placebo Minocycline

PLACEBO COMPARATOR

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; Other: Placebo Minocycline

Interventions

Hydrogen DRUG

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.

Also known as: H2

Hydrogen/Minocycline

Minocycline DRUG

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.

Also known as: Minocin, Minomycin, Akamin

Hydrogen/Minocycline

Placebo Hydrogen OTHER

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.

Placebo Hydrogen/Placebo Minocycline

Placebo Minocycline OTHER

Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.

Placebo Hydrogen/Placebo Minocycline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \. 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.
• \. 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\*

Sponsors & Collaborators

• Stony Brook University: lead

Study Sites (1)

Stony Brook University Hospital

Stony Brook, New York, 11794-8121, United States

Location

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Hydrogen; Minocycline

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Elements; Inorganic Chemicals; Gases; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Christine Pol
• Organization: Stony Brook Medicine

christiana.pol@stonybrookmedicine.edu

6314449083

Study Officials

• Dennis Choi, MD, PhD

  Stony Brook University Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor of Neurology

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: October 24, 2017
• Study Start: August 2, 2017
• Primary Completion: August 13, 2019
• Study Completion: August 13, 2019
• Last Updated: December 19, 2023
• Results First Posted: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)