Cardiac DiseasePhase 1/2NCT01727167
CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle
A Phase 1/2 study testing 200ppm CO for one hour in people with Cardiac Disease and Mitochondrial Biogenesis, run by John J Freiberger at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Cardiac Disease, Mitochondrial Biogenesis, Carbon Monoxide
- What is being tested?
- 200ppm CO for one hour
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Mar 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to consent
- Competent adult
- Scheduled to undergo aortic or mitral valve surgery only, not combined valve / revascularization procedures.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiac Disease, Mitochondrial Biogenesis, Carbon Monoxide
- Being tested
- 200ppm CO for one hour, Control
- Keywords
- cardiac disease, mitochondrial biogenesis, carbon monoxide
- Medical subject headings
- Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
200ppm CO for one hourDrug
Also called CO exposure
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.
ControlOther
This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 200ppm CO for one hour |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 weeks
Secondary outcomes (1)
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.
Measured: on week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2012 (estimated)
- Study startFeb 2014
- Primary completionJan 2016
- Study completionMar 2016
Why it stopped: Lack of funding and low accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiac DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- John J Freiberger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John J Freiberger, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01727167
- Sponsor's protocol ID
- Pro00031899
- Status last verified
- May 2016
- First submitted
- 12 Nov 2012
- Last updated
- 19 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Only one subject was recruited. Funding was not obtained. The study was cancelled with the Duke IRB 3/16.
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Low Level Carbon Monoxide Preconditioning on Human Mitochondrial Biogenesis in Aortic Valve Surgery Patients
- ClinicalTrials.gov ID
- NCT01727167
- Acronym / sponsor ID
- Pro00031899
- Conditions
- Cardiac Disease, Mitochondrial Biogenesis, Carbon Monoxide
- Keywords
- cardiac disease, mitochondrial biogenesis, carbon monoxide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding and low accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- John J FreibergerUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 15 Nov 2012 (estimated)
- Results
- Posted 19 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Placebo comparator | Other: ControlThis group will breath room air for one hour per day over the course of the three days immediately prior to surgery. |
| CO group | Experimental | Drug: 200ppm CO for one hourThis group will breath 200 ppm of CO for one hour per day over the course of the three days immediately prior to surgery. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Able to consent
- Competent adult
- Scheduled to undergo aortic or mitral valve surgery only, not combined valve / revascularization procedures.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 200ppm CO for one hourAlso: CO exposureThis is the study intervention. The treatment group will breath 200 ppm of CO for one hour over the three days immediately prior to surgery. | Drug | CO group |
| ControlThis group will breath room air for one hour per day over the course of the three days immediately prior to surgery. | Other | Control Group |
Primary outcome
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
1 secondary outcome
Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis
Time frame: on week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Only one subject was recruited. Funding was not obtained. The study was cancelled with the Duke IRB 3/16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 200ppm CO for one hour in people with Cardiac Disease and Mitochondrial Biogenesis, run by John J Freiberger at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biochemical Markers for Mitochondrial Biogenesis (Blood and Right Atrial Tissue) (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2016.