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CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01727167
Recruitment Status : Terminated (Lack of funding and low accrual.)
First Posted : November 15, 2012
Results First Posted : May 19, 2016
Last Update Posted : May 19, 2016
Information provided by (Responsible Party):
John J Freiberger, Duke University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cardiac Disease Mitochondrial Biogenesis Carbon Monoxide Drug: 200ppm CO for one hour Other: Control Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Low Level Carbon Monoxide Preconditioning on Human Mitochondrial Biogenesis in Aortic Valve Surgery Patients
Study Start Date : February 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : March 2016

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.
Other: Control
This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.

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.
Drug: 200ppm CO for one hour
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 Name: CO exposure

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Able to consent
  2. Competent adult
  3. Scheduled to undergo aortic or mitral valve surgery only, not combined valve / revascularization procedures.

Exclusion Criteria:

  1. Unable to consent
  2. Tobacco use
  3. Unanticipated medical diagnoses made at the time of surgery which require further procedures lengthening OR time and complexity above that of AVR alone.
  4. Concomitant coronary artery disease.
  5. Renal dialysis
  6. Hemodynamic instability
  7. End stage COPD defined as requiring home oxygen
  8. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01727167

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United States, North Carolina
Duke Hospital
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
John J Freiberger
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Responsible Party: John J Freiberger, Associate Professor of Anesthesiology, Duke University Identifier: NCT01727167    
Other Study ID Numbers: Pro00031899
First Posted: November 15, 2012    Key Record Dates
Results First Posted: May 19, 2016
Last Update Posted: May 19, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Only one subject was recruited. Funding was not obtained. The study was cancelled with the Duke IRB 3/16.
Keywords provided by John J Freiberger, Duke University:
cardiac disease
mitochondrial biogenesis
carbon monoxide
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases