Histamine Glutamate Antagonism in Stroke

Cerebral Edema Clinical Trial

Official title:

Glutaminergic and Histaminergic Pathway Modulation in Acute Ischemic Stroke as an Effective Neuroprotection Strategy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02142712
• Other study ID #: 201400353
• Status: Completed
• Phase: Phase 2
• First received: May 9, 2014
• Last updated: November 10, 2015
• Start date: December 2014
• Est. completion date: December 2014

Study information

• Verified date: November 2015
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Cerebrovascular Accident
• Brain Edema
• Cerebral Edema
• Stroke

Intervention

Drug:
• Diphenhydramine
Diphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care.
• Pantoprazole
Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care.
• Famotidine
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
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.

Locations

Country	Name	City	State
United States	Shands Hospital at University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CT or MRI of Head Without Contrast	MRI of head or CT head done as part of your follow up care at 3 months. This will give us the information about the effect of dextromethorphan effect on the final brain damage from stroke.	At 3 months from baseline	No
Primary	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; No significant disability despite symptoms; able to carry out all usual duties and activities; Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; Moderate disability; requiring some help, but able to walk without assistance; Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; Severe disability; bedridden, incontinent and requiring constant nursing care and attention; Dead	8 days and 3 months from the baseline	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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: presence or absence of fecal incontinence; presence or absence of urinary incontinence; help needed with grooming; help needed with toilet use; help needed with feeding; help needed with transfers (e.g. from chair to bed); help needed with walking; help needed with dressing; help needed with climbing stairs; help needed with bathing	At 3 months from baseline	No