Hyperbaric Oxygen for Carbon Monoxide Induced Chronic Encephalopathy

Description:

1. Project title Hyperbaric Oxygen for Carbon Monoxide induced Chronic Encephalopathy

2. Principle investigator(s) Jeffrey Cooper, MD Diego Torres-Russo, MD

3. Participating institution(s) UNMC, Departments of Emergency Medicine and Neurology

4. Study aims, hypotheses, methods (brief overview of design, sample, measures, budget and
statistical analysis plan)

a. 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.

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.

b. Sample i. Ages: 10-90 ii. CO induced neurological or cognitive sequelae assessed as
at least mild (e.g. UPDRS part 3 (motor)>15).

2. chronicity- signs or symptoms present for greater than one year after exposure.

iii. Exclusions:

1. 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)

2. Pregnancy

3. routine contraindications to hyperbaric oxygen (refer to NM policy HM04) c. Measures i.
Primary Outcome: Sf36

1. The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health
ii. Secondary Outcomes

1. Updrs part 3 (motor function)

1. Unified Parkinson Disease Rating Scale

2. BARS- Brief Ataxia Rating Scale

3. FMDRS a. Fahn-Marsden Dystonia Rating Scale

4. Physician assessment

5. 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

5. One-year deliverables

a. 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.

6. How the project advances clinical and translational research

1. 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.

2. 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.

7. 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.

Condition:

Carbon Monoxide Poisoning

Treatment:

hyperbaric oxygen and sham hyperbaric oxygen

Start Date:

July 31, 2020

Sponsor:

University of Nebraska

For More Information:

https://clinicaltrials.gov/show/NCT04118491

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