Histamine Glutamate Antagonism in Stroke

NCT02142712 | Completed Phase 2 Results

• 1 other identifier: 201400353
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Cerebrovascular Accident; Cerebral Edema

Keywords

Ischemic Stroke; Brain Edema; Diphenhydramine; Dextromethorphan; Famotidine

Outcome Measures

Primary Outcomes (4)

• Modified Rankin Score

  The modified Rankin Scale (m-RS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people after they have suffered a stroke.It is one of the most widely used clinical outcome measure for stroke clinical trials. The score is given according to following scale. 0- No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead

  8 days and 3 months from the baseline

• National Institutes of Health Stroke Severity (NIHSS) Scale

  NIHSS is a tool used by healthcare providers to objectively quantify the degree of impairment caused by a stroke. It is composed of 11 items. Each item scores a specific ability between a score of 0-4. Usually, for each item, a score of 0 indicates normal function in that specific ability, while a higher score indicates some level of impairment. The individual scores from each item are added together to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.

  Baseline

• Glasgow Coma Scale (GCS)

  Glasgow Coma Scale (GCS) is assessed by physical neurological examination of the subject by a qualified neurologist. GSC is a common scoring system used to describe the level of consciousness in a person following a traumatic brain injury. The initial score correlates with the severity of brain injury and prognosis. It estimates Coma severity based on Eye (4), Verbal (5), and Motor (6) criteria with the following total score of between 3 (indicating deep unconsciousness) and 15 (indicating no issues).

  Baseline

• Barthel Index

  It is an ordinal scale used to measure performance in activities of daily living (ADL). Each performance item is rated on this scale with a given number of points assigned to each level or ranking. It uses ten variables describing ADL and mobility. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. It yields a score of 0-20. The ten variables addressed in the Barthel scale are: 1. presence or absence of fecal incontinence 2. presence or absence of urinary incontinence 3. help needed with grooming 4. help needed with toilet use 5. help needed with feeding 6. help needed with transfers (e.g. from chair to bed) 7. help needed with walking 8. help needed with dressing 9. help needed with climbing stairs 10. help needed with bathing

  At 3 months from baseline

Other Outcomes (1)

• CT or MRI of Head Without Contrast

  At 3 months from baseline

Study Arms (4)

Pantoprazole

ACTIVE COMPARATOR

Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care.

Drug: Pantoprazole

Famotidine

ACTIVE COMPARATOR

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.

Drug: Famotidine

Dextromethorphan

EXPERIMENTAL

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.

Drug: Famotidine; Drug: Dextromethorphan

Diphenhydramine

EXPERIMENTAL

Diphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care.

Drug: Diphenhydramine; Drug: Famotidine

Interventions

Diphenhydramine DRUG

Diphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care.

Also known as: Benadryl

Diphenhydramine

Pantoprazole DRUG

Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care.

Also known as: Protonix

Pantoprazole

Famotidine DRUG

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.

Also known as: Pepcid

Dextromethorphan; Diphenhydramine; Famotidine

Dextromethorphan DRUG

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.

Also known as: Diamox

Dextromethorphan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

Shands Hospital at University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Stroke; Brain Edema; Ischemic Stroke

Interventions

Diphenhydramine; Pantoprazole; Famotidine; Dextromethorphan; Acetazolamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Thiadiazoles

Results Point of Contact

• Title: Dr. Vishnumurthy Shushrutha Hedna
• Organization: University of New Mexico - Neurology Department

Drshushrutha@gmail.com

505-272-3342

Study Officials

• Vishnumurthy S Hedna, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: May 20, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 15, 2015
• Results First Posted: December 15, 2015

Record last verified: 2015-11

Locations

US (1)