CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle

NCT01727167 | Terminated Phase 1 Results

• 1 other identifier: Pro00031899
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Disease; Mitochondrial Biogenesis; Carbon Monoxide

Keywords

cardiac disease; mitochondrial biogenesis; carbon monoxide

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis

  on week

Study Arms (2)

Control Group

PLACEBO COMPARATOR

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

Other: Control

CO group

EXPERIMENTAL

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

Interventions

200ppm CO for one hour DRUG

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.

Also known as: CO exposure

CO group

Control OTHER

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

Control Group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• John J Freiberger: lead

Study Sites (1)

Duke Hospital

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Heart Diseases

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Limitations and Caveats

Terminated study due to low accrual.

Results Point of Contact

• Title: John J. Freiberger, M.D.
• Organization: Duke University Medical Center

john.freiberger@duke.edu

919-684-6726

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 15, 2012
• Study Start: February 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 19, 2016
• Results First Posted: May 19, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)