Carbon Monoxide Therapy for Severe Pulmonary Arterial Hypertension
| Status: | Withdrawn |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/10/2017 |
| Start Date: | July 2012 |
| End Date: | December 2018 |
The purpose of this study is to examine the potential of carbon monoxide (CO) to decrease
elevated blood pressure in the pulmonary artery. This symptom is seen in patients with
pulmonary arterial hypertension, a rare disease that causes fatigue, dizziness, and
shortness of breath because the blood vessels that supply the lungs narrow, forcing the
heart to work harder to push blood through. Previous studies in the laboratory have shown
that carbon monoxide has promise in treating these symptoms.
Subjects in this study are being asked to undergo a new type of treatment to improve
pulmonary arterial hypertension by breathing CO gas. CO is a colorless, tasteless, odorless
gas usually found in car exhaust or cigarette smoke. It is administered with a continuous
flow of air. Subjects will undergo a screening process during which it will be determined if
they are eligible for the study. After the screening process, if subjects meet eligibility
criteria for the study, they will begin carbon monoxide treatment through a cushioned mask
that is placed over the nose and mouth. This treatment will last for sixteen weeks.
elevated blood pressure in the pulmonary artery. This symptom is seen in patients with
pulmonary arterial hypertension, a rare disease that causes fatigue, dizziness, and
shortness of breath because the blood vessels that supply the lungs narrow, forcing the
heart to work harder to push blood through. Previous studies in the laboratory have shown
that carbon monoxide has promise in treating these symptoms.
Subjects in this study are being asked to undergo a new type of treatment to improve
pulmonary arterial hypertension by breathing CO gas. CO is a colorless, tasteless, odorless
gas usually found in car exhaust or cigarette smoke. It is administered with a continuous
flow of air. Subjects will undergo a screening process during which it will be determined if
they are eligible for the study. After the screening process, if subjects meet eligibility
criteria for the study, they will begin carbon monoxide treatment through a cushioned mask
that is placed over the nose and mouth. This treatment will last for sixteen weeks.
Pulmonary arterial hypertension (PAH) remains an uncommon debilitating and fatal disease,
and is clinically marked by a progressive increase in pulmonary vascular resistance leading
to right heart failure and ultimately death. Currently the treatment options available for
those suffering from PAH target cellular dysfunction that leads to constriction of the
vasculature. Although there is some evidence that available therapies have secondary effects
on vascular remodeling there are currently no therapies that target abnormal cell
proliferation in PAH.
Carbon monoxide (CO) is a gaseous molecule with known toxicity and lethality to living
organisms when exposed to high concentrations for sustained periods. However, CO has shown
promise in preclinical models of pulmonary hypertension. Recent studies have shown that
mammalian cells have the ability to generate endogenous CO primarily through the catalysis
of heme by the heme oxygenase enzymatic system and there is ample evidence demonstrating
that CO behaves as a signaling molecule in cellular and biological processes. Furthermore,
CO has been demonstrated to exert key physiological and protective functions in various
models of tissue inflammation and injury.
This study will evaluate the safety and potential efficacy of inhaled CO in subjects with
severe PAH. Over forty subjects with severe PAH despite best available therapy will be
screened from the UIC pulmonary vascular disease clinic, of which twenty subjects will be
recruited for participation in the trial. The trial will consist of an initial screening
period to determine subjects' eligibility for the study. This will be based on a previous
echocardiogram, a six minute walk test and right heart catheterization done as part of
standard care for subjects with pulmonary arterial hypertension. Following the initial
screening, the trial will last sixteen weeks, during which subjects will receive inhaled
carbon monoxide up to three times weekly at the University of Illinois at Chicago.
and is clinically marked by a progressive increase in pulmonary vascular resistance leading
to right heart failure and ultimately death. Currently the treatment options available for
those suffering from PAH target cellular dysfunction that leads to constriction of the
vasculature. Although there is some evidence that available therapies have secondary effects
on vascular remodeling there are currently no therapies that target abnormal cell
proliferation in PAH.
Carbon monoxide (CO) is a gaseous molecule with known toxicity and lethality to living
organisms when exposed to high concentrations for sustained periods. However, CO has shown
promise in preclinical models of pulmonary hypertension. Recent studies have shown that
mammalian cells have the ability to generate endogenous CO primarily through the catalysis
of heme by the heme oxygenase enzymatic system and there is ample evidence demonstrating
that CO behaves as a signaling molecule in cellular and biological processes. Furthermore,
CO has been demonstrated to exert key physiological and protective functions in various
models of tissue inflammation and injury.
This study will evaluate the safety and potential efficacy of inhaled CO in subjects with
severe PAH. Over forty subjects with severe PAH despite best available therapy will be
screened from the UIC pulmonary vascular disease clinic, of which twenty subjects will be
recruited for participation in the trial. The trial will consist of an initial screening
period to determine subjects' eligibility for the study. This will be based on a previous
echocardiogram, a six minute walk test and right heart catheterization done as part of
standard care for subjects with pulmonary arterial hypertension. Following the initial
screening, the trial will last sixteen weeks, during which subjects will receive inhaled
carbon monoxide up to three times weekly at the University of Illinois at Chicago.
Inclusion Criteria:
- male and female ≥ 18 years old , with Pulmonary Arterial Hypertension
- Right heart catheterization diagnosis of PAH:
- Mean Pulmonary Artery Pressure (mPAP)> 25 mmHg at rest
- Pulmonary Capillary Occlusion Pressure (PCOP) or Left Ventricular End Diastolic
Pressure (LVEDP) < 15 mmHg
- Pulmonary Vascular Resistance (PVR) > 3 mmHg/L/min
- Must be Class 1.1, 1.2, or 1.3 PAH (see Appendix A)
- Echocardiographic evidence of Right Ventricular Dysfunction
- On standard and stable PAH therapy (no dose changes in the 4 weeks prior to starting
the study medication) including:
- A Prostacyclin (IV epoprostenol, IV or subcutaneous remodulin, inhaled iloprost
or remodulin) unless willing or unable to tolerate therapy AND
- Phosphodiesterase type 5 inhibitor OR
- Endothelin Receptor Antagonist OR
- Any combination of a-c
- NYHA class III or IV despite 3 months of stable therapy as outlined above
- 6 minute walk distance ≤ 380m
- Negative serum pregnancy test
- Female of childbearing age either surgically sterilized or using acceptable method of
contraception. Acceptable methods of contraception include oral contraceptives, IUD,
or other barrier methods of contraception.
Exclusion Criteria:
- History of malignancy in 2 years prior to enrollment
- Baseline cytopenia's:
- White blood cell count ≤ 3,000 i. Absolute Neutrophil Count (ANC) less than 1500
cells/mm3
- Hemoglobin ≤ 7
- Platelet ≤ 100,000
- Baseline Liver Disease:
- ALT/AST, ALk phos > 2.5x ULN, INR > 1.5
- Bilirubin > 1.5 x ULN
- Coronary artery disease
- Any cause of pulmonary hypertension other than class 1.1, 1.2, or 1.3 PAH.
- Baseline Renal Disease: Cr ≥ 2
- Active Smoker
- Hypoxemia with SaO2 < 95% on oxygen 2 L/min
- Baseline COHb > 2%
- Pregnancy or lactation
- Inability to attend scheduled clinic visits
- Previous lung transplant
- Naive to available standard PAH therapy
- Pulmonary Capillary Occlusion Pressure (PCOP) or LEft Ventricular End Diastolic
Pressure (LVEDP)< 15 mmHg
- Concomitant enrollment in another investigational treatment protocol for PAH or
taking any off label drug therapy for PAH
- Recent enrollment in or plans to enroll in Pulmonary Rehabilitation during the study
period
- Any condition that in the opinion of the investigator would prevent completion of
study procedures
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