HACMICE: Hyperbaric Oxygen for Carbon Monoxide Induced Chronic Encephalopathy
Study Details
Study Description
Brief Summary
in some patients, a few days or weeks after they recover from carbon monoxide poisoning they develop new symptoms. These can affect mood, ability to think or remember clearly, and movements. Some people develop movement problems that are similar to Parkinson's disease. This damage to brain tissue is called "encephalopathy," and this study will look at the effect of pressurized oxygen therapy on long term, or chronic, encephalopathy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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Project title Hyperbaric Oxygen for Carbon Monoxide induced Chronic Encephalopathy
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Principle investigator(s) Jeffrey Cooper, MD Diego Torres-Russo, MD
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Participating institution(s) UNMC, Departments of Emergency Medicine and Neurology
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Study aims, hypotheses, methods (brief overview of design, sample, measures, budget and statistical analysis plan)
- Design i. prospective, blinded sham controlled crossover study. ii. N=10 iii. We will divide the subjects into two groups of five. One group will receive 40 Hyperbaric Oxygen (HBO2) treatments (100% oxygen at twice normal air pressure (2 ATA)) followed by 40 sham HBO2 treatments (air at near normal pressure (1.2 ATA)). Treatments will be done once daily for 2 hours, Monday through Friday. The second block will be treated similarly except that they will receive sham treatments in the first block and oxygen treatments in the second block.
- Neurological and psychologic assessments will be done prior to starting treatments, after the first block of 40 and again after the second block of 40.
- Sample i. Ages: 10-90 ii. CO induced neurological or cognitive sequelae assessed as at least mild (e.g. UPDRS part 3 (motor)>15).
- chronicity- signs or symptoms present for greater than one year after exposure.
- Exclusions:
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other morbidities which may contribute to chronic neurocognitive deficits such as traumatic brain injury, poisoning by other toxins, other neurodegenerative diseases (e.g. Parkinson's disease)
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Pregnancy
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routine contraindications to hyperbaric oxygen (refer to NM policy HM04) c. Measures i. Primary Outcome: Sf36
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The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health
- Secondary Outcomes
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Updrs part 3 (motor function)
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Unified Parkinson Disease Rating Scale
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BARS- Brief Ataxia Rating Scale
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FMDRS a. Fahn-Marsden Dystonia Rating Scale
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Physician assessment
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Moca a. The Montreal Cognitive Assessment- a brief cognitive screening tool for Mild Cognitive Impairment d. Budget i. Nebraska Medicine has not yet given us a cost per treatment rate but we estimate $300 each yielding:10 patients @ 80 treatments @ $300=$240,000 e. Statistics i. We will analyze this using standard linear crossover model techniques on the primary outcome (SF36) as well as the secondary rating scales (UPDRS, BARS, MOCA, FMDRS) ii. N=10 will be enough to establish mean responses and standard deviations in order to establish effect sizes to power a future study and to demonstrate the promise of HBO2 rather than establish statistical significance
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One-year deliverables
- Study approved by IRB b. patient recruitment almost done c. several subjects completed d. We anticipate data collection and study completed by the end of year two.
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How the project advances clinical and translational research
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Basic science research has established that hyperbaric medicine has a number of potentially useful effects in healing the injured brain including stem cell migration, fibroblast proliferation, angiogenesis and neurogenesis in areas of infarct. Case reports and some small, poorly controlled clinical trials have shown favorable results in traumatic brain injury, CO induced encephalopathy, and stroke as well as in chronic issues such as cerebral palsy.
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This project looks specifically at CO induced chronic brain injury in a blinded and controlled fashion as a next step in providing an efficacious treatment option for an otherwise untreatable condition. If positive results, a larger study would be needed to confirm its findings.
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Lay summary of project, including disease/health relevance Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in the United States. After a period of apparent recovery, survivors of acute CO-poisoning can develop a potentially permanent neurologic deterioration (DNS). DNS is a rare, poorly known encephalopathy with a 25-50% prevalence among severely poisoned CO-poisoned patients. Its symptoms and signs range from subtle abnormalities to severe dementia, Parkinsonism, gait disturbances, mutism, and incontinence. Recovery from delayed neuropsychiatric syndrome occurs in 50-75% of patients within 1 year. However, this leaves 25-50% permanently impaired. Hyperbaric oxygen therapy (HBO2) is useful after acute poisoning to reduce the chance of developing DNS. However, appropriate therapy for DNS is widely debated; particularly, the role of hyperbaric oxygen therapy (HBO2) after DNS has developed is controversial.
There are research efforts looking into HBO2 for other forms of brain injury such as trauma, stroke, cerebral palsy and other chronic neurological disorders. We have reported on a patient treated with remarkable success who was gravely disabled 14 months from his CO poisoning. A few other similar reports exist in the medical literature. We, therefore, propose to ascertain whether hyperbaric oxygen is efficacious in the treatment of chronic DNS brain injury from carbon monoxide (CO) poisoning.
As a pilot study, we intend to recruit, as subjects, ten patients suffering from DNS for longer than one year. This will be a prospective, blinded sham controlled crossover study. We will divide the subjects into two groups of five. One group will receive 40 HBO2 treatments (100% oxygen at twice normal air pressure (2 ATA)) followed by 40 sham HBO2 treatments (air at near normal pressure (1.2 ATA)). Treatments will be done once daily for 2 hours, Monday through Friday. Neurological and psychologic assessments will be done prior to starting treatments, after the first block of 40 and again after the second block of 40. The second block will be treated similarly except that they will receive sham treatments in the first block and oxygen treatments in the second block. In this manner, all patients will receive treatment which we believe is therapeutic. All patients will act as both experimental and control subject.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Sham Comparator: sham1st 40 sham HBO2 treatments (air at near normal pressure (1.2 ATA)). Treatments will be done once daily for 2 hours, Monday through Friday. The second block will be treated similarly except that they will receive sham treatments in the first block and oxygen treatments in the second block. |
Device: hyperbaric oxygen and sham hyperbaric oxygen
see arm descriptions
|
| Active Comparator: sham second iii. We will divide the subjects into two groups of five. One group will receive 40 Hyperbaric Oxygen (HBO2) treatments (100% oxygen at twice normal air pressure (2 ATA)) followed by 40 sham HBO2 treatments (air at near normal pressure (1.2 ATA)). Treatments will be done once daily for 2 hours, Monday through Friday. The second block will be treated similarly except that they will receive sham treatments in the first block and oxygen treatments in the second block. iv. Neurological and psychologic assessments will be done prior to starting treatments, after the first block of 40 and again after the second block of 40. |
Device: hyperbaric oxygen and sham hyperbaric oxygen
see arm descriptions
|
Outcome Measures
Primary Outcome Measures
- Short Form (36) Health Survey [4 months (after 80 treatments)]
is a 36-item, patient-reported survey of patient health
Secondary Outcome Measures
- Updrs part 3 (motor function) [0, 2 and 4 months: (prior to study, after 40 treatments and 80 treatments)]
Unified Parkinson Disease Rating Scale
- BARS- Brief Ataxia Rating Scale [0, 2 and 4 months: (prior to study, after 40 treatments and 80 treatments)]
an assessment of ataxia, 30 point scale with 0 being normal
- Fahn-Marsden Dystonia Rating Scale [0, 2 and 4 months: (prior to study, after 40 treatments and 80 treatments)]
an assessment of dystonia, 120 point scale with 0 being normal
- Physician assessment [prior to study, after 40 treatments and 80 treatments (0, 2 and 4 months)]
an assessment of global function, this is a verbal description not a scale
- The Montreal Cognitive Assessment [0, 2 and 4 months: (prior to study, after 40 treatments and 80 treatments)]
a brief cognitive screening tool for Mild Cognitive Impairment
- Short Form (36) Health Survey [0, 2 and 4 months: (prior to study, after 40 treatments and 80 treatments)]
is a 36-item, patient-reported survey of patient health
Eligibility Criteria
Criteria
Inclusion Criteria:
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CO induced neurological or cognitive sequelae assessed as at least mild (e.g. UPDRS part 3 (motor)>15).
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chronicity- signs or symptoms present for greater than one year after exposure.
Exclusion Criteria:
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age >90 or less than 10 years
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other morbidities which may contribute to chronic neurocognitive deficits (such as traumatic brain injury, poisoning by other toxins, other neurodegenerative diseases)
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pregnancy (if a subject becomes pregnant she will be removed from the study)
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routine contraindications to hyperbaric oxygen
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Nebraska
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 225-18-FB