Cardiac Allograft VasculopathyPhase 1NCT01848301
Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
A Phase 1 study testing Optical Coherence Tomography, Acetylcholine and Brachial Artery Flow Mediated Dilation in people with Cardiac Allograft Vasculopathy and Antibody Mediated Rejection, run by Gladwin, Mark, MD at 1 site in United States.
Trial summary
Coronary allograft vasculopathy (CAV) is the leading cause of late graft failure and second leading cause of late mortality after heart transplantation. CAV has been associated with a variety of traditional risk factors for atherosclerosis; however, immune mediated injury from development of de-novo donor-specific… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cardiac Allograft Vasculopathy, Antibody Mediated Rejection
- What is being tested?
- Optical Coherence Tomography, Acetylcholine and Brachial Artery Flow Mediated Dilation
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to 1 May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects who are 1 year post heart transplantation
- Subjects will include both male and females
- Be at least 18 years of age
Who cannot join
- Known coronary artery disease after transplantation
- Evidence of strong or moderate antibodies already present at the time of the transplant
- Severe renal dysfunction defined as creatinine clearance of <30 or on hemodialysis.
- 3 or more episodes of acute cellular rejection
- Females who are pregnant
- Patients requiring endomyocardial biopsy at the time of catheterization
Show all 9Show fewer
- Patients unable to tolerate heparin or systemic anticoagulation
- History of multi-organ transplant
- Patients unable to give consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Coronary allograft vasculopathy (CAV) is the leading cause of late graft failure and second leading cause of late mortality after heart transplantation. CAV has been associated with a variety of traditional risk factors for atherosclerosis; however, immune mediated injury from development of de-novo donor-specific antibodies after transplantation also likely plays an important role. Similar to the progression of traditional atherosclerosis, it is likely that endothelial dysfunction is the precursor to the development of intimal thickening and CAV.
The investigators hypothesize that coronary allograft vasculopathy after heart transplantation as defined by progressive neointimal hyperplasia is preceded by endothelial dysfunction, which in turn is at least partly mediated by donor specific antibodies.
The investigators are proposing a prospective study in humans to test the above hypothesis and further mechanistically understand how CAV progresses. In this study the investigators will test for coronary endothelial function by infusing acetylcholine into the coronary artery and measure intimal hyperplasia by optical coherence tomography (OCT) and compare findings in patients with and without donor specific antibodies.
- Being tested
- Optical Coherence Tomography, Acetylcholine, Brachial Artery Flow Mediated Dilation
- Keywords
- Optical Coherence Tomography, OCT, Coronary Allograft Vasculopathy, Donor Specific Antibodies, Acetylcholine, Coronary endothelial function, Brachial Artery Flow Mediated Dilation, Heart transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optical Coherence TomographyDevice
Also called OCT
OCT imaging of the LAD coronary artery
AcetylcholineDrug
Also called Miochol, Miochol-e
Infusion in the coronary artery to study endothelial function
Brachial Artery Flow Mediated DilationProcedure or surgery
Assess peripheral brachial artery endothelial function
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | All subjects will undergo a Brachial Artery Flow Medicated Dilation prior to heart catheterization. After routine heart catheterization, images of their coronary artery will be recorded by Optical Coherence Tomography (OCT) during infusion of Acetylcholine. Receives: Device: Optical Coherence Tomography; Drug: Acetylcholine; Procedure: Brachial Artery Flow Mediated Dilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be a comparison of intimal thickness in the coronary artery by Optical Coherence Tomography with presence or absence of donor specific antibodies.
Measured: baseline (year 1 post transplant) and annually for 2 years
Secondary outcomes (6)
Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function.
Measured: baseline (year 1 post transplant) and annually for 2 years
Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening.
Measured: baseline (year 1 post transplant) and annually for 2 years
Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness.
Measured: baseline (year 1 post transplant) and annually for 2 years
Plaque characterization in coronary artery by OCT
Measured: baseline (year 1 post transplant) and annually for 2 years
Natural progression of coronary allograft vasculopathy over first 2 years after transplantation
Measured: baseline (year 1 post transplant) and annually for 2 years
Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies.
Measured: baseline (year 1 post transplant) and annually for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startSep 2012
- Primary completionSep 2014
- Study completion1 May 2017
Why it stopped: loss of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac Allograft VasculopathyStudies 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
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gladwin, Mark, MD
- Responsible party
- Principal investigator, Catalin Toma, MD, University of Pittsburgh
- Investigators
- Catalin Toma, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01848301
- Sponsor's protocol ID
- PRO12060201
- Other IDs
- American Heart Association
- Status last verified
- Sep 2017
- First submitted
- 2 May 2013
- Last updated
- 6 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Khandhar SJ, Yamamoto H, Teuteberg JJ, Shullo MA, Bezerra HG, Costa MA, Selzer F, Lee JS, Marroquin OC, McNamara DM, Mulukutla SR, Toma C. Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study). J Heart Lung Transplant. 2013 Jun;32(6):596-602. doi: 10.1016/j.healun.2013.02.005. Epub 2013 Mar 15.
PubMed 23499356
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
- ClinicalTrials.gov ID
- NCT01848301
- Acronym / sponsor ID
- PRO12060201
- Keywords
- Optical Coherence Tomography, OCT, Coronary Allograft Vasculopathy, Donor Specific Antibodies, Acetylcholine, Coronary endothelial function, Brachial Artery Flow Mediated Dilation, Heart transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: loss of funding
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Gladwin, Mark, MD
- Study start
- Sep 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- 1 May 2017 (actual)
- First posted
- 7 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary allograft vasculopathy (CAV) is the leading cause of late graft failure and second leading cause of late mortality after heart transplantation. CAV has been associated with a variety of traditional risk factors for atherosclerosis; however, immune mediated injury from development of de-novo donor-specific antibodies after transplantation also likely plays an important role. Similar to the progression of traditional atherosclerosis, it is likely that endothelial dysfunction is the precursor to the development of intimal thickening and CAV.
The investigators hypothesize that coronary allograft vasculopathy after heart transplantation as defined by progressive neointimal hyperplasia is preceded by endothelial dysfunction, which in turn is at least partly mediated by donor specific antibodies.
The investigators are proposing a prospective study in humans to test the above hypothesis and further mechanistically understand how CAV progresses. In this study the investigators will test for coronary endothelial function by infusing acetylcholine into the coronary artery and measure intimal hyperplasia by optical coherence tomography (OCT) and compare findings in patients with and without donor specific antibodies.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Device: Optical Coherence Tomography, Drug: Acetylcholine, Procedure: Brachial Artery Flow Mediated DilationAll subjects will undergo a Brachial Artery Flow Medicated Dilation prior to heart catheterization. After routine heart catheterization, images of their coronary artery will be recorded by Optical Coherence Tomography (OCT) during infusion of Acetylcholine. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects who are 1 year post heart transplantation
- Subjects will include both male and females
- Be at least 18 years of age
Key exclusion criteria (9 listed)
- Known coronary artery disease after transplantation
- Evidence of strong or moderate antibodies already present at the time of the transplant
- Severe renal dysfunction defined as creatinine clearance of <30 or on hemodialysis.
- 3 or more episodes of acute cellular rejection
- Females who are pregnant
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 |
|---|---|---|
| Optical Coherence TomographyAlso: OCTOCT imaging of the LAD coronary artery | Device | Single arm |
| AcetylcholineAlso: Miochol, Miochol-eInfusion in the coronary artery to study endothelial function | Drug | Single arm |
| Brachial Artery Flow Mediated DilationAssess peripheral brachial artery endothelial function | Procedure or surgery | Single arm |
Primary outcome
The primary endpoint will be a comparison of intimal thickness in the coronary artery by Optical Coherence Tomography with presence or absence of donor specific antibodies.
Time frame: baseline (year 1 post transplant) and annually for 2 years
6 secondary outcomes
Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function.
Time frame: baseline (year 1 post transplant) and annually for 2 years
Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening.
Time frame: baseline (year 1 post transplant) and annually for 2 years
Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness.
Time frame: baseline (year 1 post transplant) and annually for 2 years
Plaque characterization in coronary artery by OCT
Time frame: baseline (year 1 post transplant) and annually for 2 years
Natural progression of coronary allograft vasculopathy over first 2 years after transplantation
Time frame: baseline (year 1 post transplant) and annually for 2 years
Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies.
Time frame: baseline (year 1 post transplant) and annually for 2 years
Results and safety
The study was stopped early (reason given: loss of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
- Background: PubMed 23499356Khandhar SJ, Yamamoto H, Teuteberg JJ, Shullo MA, Bezerra HG, Costa MA, Selzer F, Lee JS, Marroquin OC, McNamara DM, Mulukutla SR, Toma C. Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study). J Heart Lung Transplant. 2013 Jun;32(6):596-602. doi: 10.1016/j.healun.2013.02.005. Epub 2013 Mar 15.
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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.
Catalin Toma, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Optical Coherence Tomography, Acetylcholine and Brachial Artery Flow Mediated Dilation in people with Cardiac Allograft Vasculopathy and Antibody Mediated Rejection, run by Gladwin, Mark, MD 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 9 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 6 Sep 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: loss of funding). Results are not available in the source record.
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?
The primary endpoint will be a comparison of intimal thickness in the coronary artery by Optical Coherence Tomography with presence or absence of donor specific antibodies. (time frame: baseline (year 1 post transplant) and annually for 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01848301, which also lists 1 linked publication.
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 6 Sep 2017.