- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01727167
CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle
May 18, 2016 updated by: John J Freiberger
Effects of Low Level Carbon Monoxide Preconditioning on Human Mitochondrial Biogenesis in Aortic Valve Surgery Patients
This study will test if inhalation of Carbon Monoxide (CO) will increase the numbers of mitochondria in heart muscle.
Mitochondria are the small components of muscle and other cells that convert fuel and oxygen to the easily usable forms of energy (ATP) that power all cell's activities.
Adequate numbers of healthy mitochondria are essential to heart cell function.
From animal and other studies we have reason to believe that breathing small amounts of CO will signal the body to increase the numbers of mitochondria in heart cells.
We propose to test this theory in heart valve surgery patients by examining a small sample of heart tissue (from the right atrial appendage) that is routinely cut out during the preparation of the patient for cardio-pulmonary bypass and that would otherwise be discarded by the surgeon.
Muscle samples from two groups of subjects will be compared.
One group will breath CO and the other group will breath room air.
If CO is effective, we should notice an increase in the numbers of mitochondria in the group that was exposed to CO compared to the group that breathed room air.
Study Overview
Status
Terminated
Intervention / Treatment
Detailed Description
PURPOSE AND OBJECTIVE: Endogenously produced carbon monoxide (CO) is known to act as a physiologic signaling molecule to induce mitochondrial biogenesis.
This study will test if low-level CO preconditioning induces myocardial biogenesis in humans and if clinical benefit is derived from it.
STUDY ACTIVITIES AND POPULATION: The study is an interventional, prospective, randomized, double-blinded trial with a 2-week follow up period.
Forty subjects will be recruited from the population of patients scheduled to undergo elective aortic valve replacement.
For safety purposes patients with coronary disease will be excluded.
Subjects meeting the inclusion criteria will be randomized to receive either air or air containing CO @ 200ppm as a one-hour inhalational treatment per day over the course of the three days immediately prior to their scheduled operation.
Biochemical markers for mitochondrial biogenesis (blood and right atrial tissue) and clinical outcome parameters ( BUN/creatinine, and left ventricular function measured by 2D echo) will be measured in all patients pre and post-operatively.
Right atrial tissue samples will be collected from tissue that is routinely excised during placement of venous cannulas for cardiopulmonary bypass.
RISK/SAFETY & DATA ANALYSIS: Risks will be those of CO inhalation and blood drawing.
The 200ppm dose chosen is within OSHA work place exposure limits and has been used safely in human subjects previously.
Data will be analyzed by comparing biogenetic marker levels and clinical parameters pre and post intervention and control to CO treatment group.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Able to consent
- Competent adult
- Scheduled to undergo aortic or mitral valve surgery only, not combined valve / revascularization procedures.
Exclusion Criteria:
- Unable to consent
- Tobacco use
- Unanticipated medical diagnoses made at the time of surgery which require further procedures lengthening OR time and complexity above that of AVR alone.
- Concomitant coronary artery disease.
- Renal dialysis
- Hemodynamic instability
- End stage COPD defined as requiring home oxygen
- By history any significant exposure to second hand smoke including living with a smoker who smokes indoors or working in a high smoking environment for 8 hours a day or more (i.e. factory or bar) will exclude subject from the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Control Group
This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.
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This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.
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EXPERIMENTAL: CO group
This group will breath 200 ppm of CO for one hour per day over the course of the three days immediately prior to surgery.
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This is the study intervention.
The treatment group will breath 200 ppm of CO for one hour over the three days immediately prior to surgery.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biochemical Markers for Mitochondrial Biogenesis (Blood and Right Atrial Tissue)
Time Frame: 2 weeks
|
Right atrial biochemical markers will be measured one time only, intra-operatively.
Blood Biochemical markers will be measured before CO exposure and at intervals up to one week post-operatively
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2 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis
Time Frame: on week
|
Biochemical markers in both right atrial tissue and blood will be measured and compared to see if the more easily obtained blood markers accurately describe changes expected in the heart.
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on week
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2014
Primary Completion (ACTUAL)
January 1, 2016
Study Completion (ACTUAL)
March 1, 2016
Study Registration Dates
First Submitted
November 12, 2012
First Submitted That Met QC Criteria
November 12, 2012
First Posted (ESTIMATE)
November 15, 2012
Study Record Updates
Last Update Posted (ESTIMATE)
May 19, 2016
Last Update Submitted That Met QC Criteria
May 18, 2016
Last Verified
May 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00031899
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
Only one subject was recruited.
Funding was not obtained.
The study was cancelled with the Duke IRB 3/16.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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