Stroke, IschemicPhase 2/3H2MNCT03320018
Neuroprotection in Acute Ischemic Stroke
A Phase 2/3 study testing Hydrogen and Minocycline in people with Stroke, Ischemic, run by Stony Brook University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Ischemic
- What is being tested?
- Hydrogen and Minocycline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2017to 13 Aug 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stony Brook University Hospital
Stony Brook, New York, 11794-8121
About this study
Official title: Pilot Study of the Neuroprotective Effects of Hydrogen and Minocycline in Acute Ischemic Stroke
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.
Read the 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).
- Conditions
- Stroke, Ischemic
- Being tested
- Hydrogen, Minocycline, Placebo Hydrogen, Placebo Minocycline
- Keywords
- neuroprotection, antioxidant
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrogenDrug
Also called H2
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.
MinocyclineDrug
Also called Minocin, Minomycin, Akamin
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.
Placebo HydrogenOther
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 MinocyclineOther
Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo Hydrogen; Other: Placebo Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (2)
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).
Measured: 45 days
NIH Stroke Scale (NIHSS)
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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start2 Aug 2017
- Primary completion13 Aug 2019
- Study completion13 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stony Brook University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kamil Stefanowski, Stony Brook University
- Investigators
- Dennis Choi, MD, PhD, Study director, Stony Brook University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03320018
- Sponsor's protocol ID
- 932805
- Acronym
- H2M
- Status last verified
- Dec 2023
- First submitted
- 20 Oct 2017
- Last updated
- 19 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Neuroprotective Effects of Hydrogen and Minocycline in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT03320018
- Acronym / sponsor ID
- H2M / 932805
- Conditions
- Stroke, Ischemic
- Keywords
- neuroprotection, antioxidant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Stony Brook UniversityUniversity, hospital or other
- Study start
- 2 Aug 2017 (actual)
- Primary completion
- 13 Aug 2019 (actual)
- Study completion
- 13 Aug 2019 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Posted 19 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydrogen/Minocycline | Experimental | Drug: Hydrogen, Drug: MinocyclineHydrogen 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. |
| Placebo Hydrogen/Placebo Minocycline | Placebo comparator | Other: Placebo Hydrogen, Other: Placebo MinocyclineNormal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrogenAlso: H2Hydrogen 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. | Drug | Hydrogen/Minocycline |
| MinocyclineAlso: Minocin, Minomycin, AkaminMinocycline 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. | Drug | Hydrogen/Minocycline |
| Placebo HydrogenNormal 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 Hydrogen/Placebo Minocycline |
| Placebo MinocyclineNormal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline. | Other | Placebo Hydrogen/Placebo Minocycline |
Primary outcome
Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq)
Time frame: 90 days
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.
2 secondary outcomes
Simplified Modified Rankin Scale (sMRSq)
Time frame: 45 days
NIH Stroke Scale (NIHSS)
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dennis Choi, MD, PhD study director
Stony Brook University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Hydrogen and Minocycline in people with Stroke, Ischemic, run by Stony Brook University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq) (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.