CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle

Cardiac Disease Clinical Trial

Official title:

Effects of Low Level Carbon Monoxide Preconditioning on Human Mitochondrial Biogenesis in Aortic Valve Surgery Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01727167
• Other study ID #: Pro00031899
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 12, 2012
• Last updated: May 18, 2016
• Start date: February 2014
• Est. completion date: March 2016

Study information

• Verified date: May 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

• Carbon Monoxide
• Cardiac Disease
• Heart Diseases
• Mitochondrial Biogenesis

Intervention

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

Locations

Country	Name	City	State
United States	Duke Hospital	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
John J Freiberger

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemical Markers for Mitochondrial Biogenesis (Blood and Right Atrial Tissue)	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	2 weeks	No
Secondary	Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis	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.	on week	No