Acute Cerebrovascular AccidentPhase 2NCT02142712
Histamine Glutamate Antagonism in Stroke
A Phase 2 study testing Diphenhydramine, Pantoprazole and Famotidine in people with Acute Cerebrovascular Accident and Cerebral Edema, run by University of Florida at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Cerebrovascular Accident, Cerebral Edema
- What is being tested?
- Diphenhydramine, Pantoprazole and Famotidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Dec 2014
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Shands Hospital at University of Florida
Gainesville, Florida, 32610
About this study
Official title: Glutaminergic and Histaminergic Pathway Modulation in Acute Ischemic Stroke as an Effective Neuroprotection Strategy.
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.
Read the 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:
- Modified Rankin Scale (m-RS) scores NIH Stroke Scale scores
- CT or MRI of the head without contrast
- Conditions
- Acute Cerebrovascular Accident, Cerebral Edema
- Being tested
- Diphenhydramine, Pantoprazole, Famotidine, Dextromethorphan
- Keywords
- Ischemic Stroke, Brain Edema, Diphenhydramine, Dextromethorphan, Famotidine
- Medical subject headings
- Stroke, Brain Edema, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiphenhydramineDrug
Also called Benadryl
Diphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care.
PantoprazoleDrug
Also called Protonix
Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care.
FamotidineDrug
Also called Pepcid
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.
DextromethorphanDrug
Also called Diamox
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.
| Study group | Role | What they receive |
|---|---|---|
| Pantoprazole | Active comparator | Pantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Diphenhydramine; Drug: Famotidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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).
Measured: 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:
- 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
Measured: At 3 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2014
- Study completionDec 2014
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 Acute Cerebrovascular AccidentStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vishnumurthy S Hedna, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02142712
- Sponsor's protocol ID
- 201400353
- Status last verified
- Nov 2015
- First submitted
- 9 May 2014
- Last updated
- 15 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutaminergic and Histaminergic Pathway Modulation in Acute Ischemic Stroke as an Effective Neuroprotection Strategy.
- ClinicalTrials.gov ID
- NCT02142712
- Acronym / sponsor ID
- 201400353
- Conditions
- Acute Cerebrovascular Accident, Cerebral Edema
- Keywords
- Ischemic Stroke, Brain Edema, Diphenhydramine, Dextromethorphan, Famotidine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 20 May 2014 (estimated)
- Results
- Posted 15 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Modified Rankin Scale (m-RS) scores NIH Stroke Scale scores
- CT or MRI of the head without contrast
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pantoprazole | Active comparator | Drug: PantoprazolePantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care. |
| Famotidine | Active comparator | Drug: FamotidineFamotidine 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 | Experimental | Drug: Famotidine, Drug: DextromethorphanDextromethorphan 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. |
| Diphenhydramine | Experimental | Drug: Diphenhydramine, Drug: FamotidineDiphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
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 |
|---|---|---|
| DiphenhydramineAlso: BenadrylDiphenhydramine 12.5 mg BID intravenous or 25 mg BID oral for 4 days along with current standard of care. | Drug | Diphenhydramine |
| PantoprazoleAlso: ProtonixPantoprazole intravenous 40mg q daily as part of standard of care for stress ulcer prophylaxis along with current standard of care. | Drug | Pantoprazole |
| FamotidineAlso: PepcidFamotidine 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 | Dextromethorphan, Diphenhydramine, Famotidine |
| DextromethorphanAlso: DiamoxDextromethorphan 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 | Dextromethorphan |
Primary outcome
Modified Rankin Score
Time frame: 8 days and 3 months from the baseline
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
National Institutes of Health Stroke Severity (NIHSS) Scale
Time frame: Baseline
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.
Glasgow Coma Scale (GCS)
Time frame: Baseline
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).
Barthel Index
Time frame: At 3 months from baseline
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Vishnumurthy S Hedna, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diphenhydramine, Pantoprazole and Famotidine in people with Acute Cerebrovascular Accident and Cerebral Edema, run by University of Florida 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 11 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 15 Dec 2015. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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 15 Dec 2015). 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?
Modified Rankin Score (time frame: 8 days and 3 months from the baseline). The study lists 4 primary outcomes in all. 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 15 Dec 2015.