Histamine Glutamate Antagonism in Stroke
Condition: Acute Cerebrovascular Accident; Cerebral Edema
MeSH terms: Stroke; Brain Edema
Intervention: Diphenhydramine; Pantoprazole; Famotidine; Dextromethorphan
Intervention description: Diphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care.; Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care.; Famotidine 40 mg intravenous BID (maximum dose of 80 mg/day) for 4 days as part of standard of care for stress ulcer prophylaxis along with current standard of care.; Dextromethorphan 60 mg QID orally (maximum dose of 240 mg/day) for 2 days (total of 4 doses) along with current standard of care. If the drug can't be given orally, then feeding tube (G-tube, NG Tube or DHT) will be used for drug administration.
Intervention MeSH terms: Diphenhydramine; Promethazine; Dextromethorphan; Pantoprazole; Famotidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Ischemic Stroke; Brain Edema; Diphenhydramine; Dextromethorphan; Famotidine

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.
    

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.