Clinical trial NCT02142712: Histamine Glutamate Antagonism in Stroke
Official title: Glutaminergic and Histaminergic Pathway Modulation in Acute Ischemic Stroke as an Effective Neuroprotection Strategy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Cerebrovascular Accident
Cerebral Edema
Keywords: Ischemic Stroke
Brain Edema
Diphenhydramine
Dextromethorphan
Famotidine
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2014-05-20
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Stroke is the 4th leading cause of death in United States with an estimated 1 death every 4 minutes. On average, someone suffers from stroke in United States every 40th second. Stroke recurs in 1 out of 4 stroke patients. About 87% of the strokes are as a result of ischemic insult. The total economic burden from stroke accounts to 38.6 billion dollars per year. Stroke is also one of the leading causes of long term disability. Current stroke therapies concentrate mainly on acute revascularization, sub-acute rehabilitation and secondary prevention.

Neuroprotection is not the mainstay of treatment modality as there are no effective regimen which has satisfied stroke clinicians and researchers. Many neuroprotection agents have shown excellent pre-clinical results but have failed in clinical translation. Thus we need to find new treatments in order to decrease the mortality and morbidity caused by stroke.

The investigators hypothesize that adopting a narrower therapeutic window, with treatment initiation in the first six hours, may demonstrate a positive or significant short and long term neuroprotective effect from NMDA/Glutaminergic or histaminergic antagonism when compared with standard of care.

Detailed description: If the subject decides to take part in this study, the subject will be placed randomly in the treatment group or the standard of care group. This means:

The subject will be given either the treatment drugs with standard of care for stroke or only standard of care. If the subject is placed in the treatment group the subject will be again randomly administered either diphenhydramine oral or through an injection in the vein for 4 days or dextromethorphan tablet orally for 2 days. In the treatment group the subject will receive another drug named famotidine through an injection in vein as a prophylaxis to prevent any gastrointestinal bleeding or ulceration whereas in the standard of care group the subject will receive pantoprazole through an injection in the vein for the same purpose. If the subject cannot take medication orally then we will put a tube through the nose to the subject's stomach or small intestine or we might also put a gastric tube directly into the subject's stomach surgically through a small cut in the belly. The investigators will collect information for the medical charts to include: imaging data, stroke assessments and medical history. A neurological exam will done, called the National Institutes of Health Stroke Scale (NIHSS). It is used to assess the neurologic damage caused by stroke. A Modified Rankin Scale (m-RS) will also be performed and this is a scale used to measure the degree of disability or dependence in the daily activities after a stroke.

The subject will be asked to come for a follow-up at 3 months after the discharge from the hospital and the following will be done:

1. Modified Rankin Scale (m-RS) scores NIH Stroke Scale scores
2. CT or MRI of the head without contrast

Eligibility criteria: Inclusion Criteria:

1. Subjects with age ≥18 years and ≤80 years at the time of screening.
2. All Ischemic stroke patients with clinical and or radiological diagnosis.
3. Subjects who have presented to hospital within 6 hours of symptom onset.
4. The subject or his/ her legal representative is willing to undergo informed consent process prior to enrollment into this study.

Exclusion Criteria:

1. Subject with age \< 18 years and \>80 years at the time of screening.
2. Time of symptom onset cannot be determined.
3. Subject who is pregnant or lactating.
4. Subject who has asthma exacerbations in past 3 months.
5. Subject who has hypersensitivity to dextromethorphan, diphenhydramine or famotidine, or other H2 antagonists or any component of the formulation.
6. Serotonin syndrome.
7. Concurrent administration with or within 2 weeks of discontinuing an MAO inhibitor
8. Subjects with renal or hepatic failure.
9. The subject or legal representative is unable to provide informed consent.
10. The subject is medically unstable to participate in the trial as determined by the principal investigator.
11. The subject has any end stage medical condition as determined by the principal investigator.

Primary outcomes:
measure: Modified Rankin Score
timeFrame: 8 days and 3 months from the baseline
measure: National Institutes of Health Stroke Severity (NIHSS) Scale
timeFrame: Baseline
measure: Glasgow Coma Scale (GCS)
timeFrame: Baseline
measure: Barthel Index
timeFrame: At 3 months from baseline
Secondary outcomes:
Other outcomes:
measure: CT or MRI of Head Without Contrast
timeFrame: At 3 months from baseline
Locations:
city: Gainesville
country: United States
facility: Shands Hospital at University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Vishnumurthy S Hedna, MD
role: PRINCIPAL_INVESTIGATOR
References: