CO Mitochondrial Biogenesis

This study is not yet open for participant recruitment.
Verified December 2013 by Duke University
Sponsor:
Information provided by (Responsible Party):
John J Freiberger, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01727167
First received: November 12, 2012
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Cardiac Disease
Mitochondrial Biogenesis
Carbon Monoxide
Drug: 200ppm CO for one hour
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Biochemical markers for mitochondrial biogenesis (blood and right atrial tissue) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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:
  • Compare blood to right atrial tissue biochemical markers of mitochondrial biogenesis [ Time Frame: on week ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control Group
This group will breath room air for one hour prior to surgery.
Experimental: CO group
This group will breath 200 ppm of CO for one hour the day 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 on the day prior to surgery.
Other Name: CO exposure

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01727167

Contacts
Contact: John J Freiberger, MD, MPH 919-684-6726 john.freiberger@duke.edu

Locations
United States, North Carolina
Duke Hospital Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: John J Freiberger, MD, MPH    919-684-6726    john.freiberger@duke.edu   
Principal Investigator: John J Freiberger, MD, MPH         
Sponsors and Collaborators
John J Freiberger
  More Information

No publications provided

Responsible Party: John J Freiberger, Asst Clin Prof Anesthesiology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01727167     History of Changes
Other Study ID Numbers: Pro00031899
Study First Received: November 12, 2012
Last Updated: December 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
cardiac disease
mitochondrial biogenesis
carbon monoxide

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases
Carbon Monoxide
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014