Cardiac Allograft VasculopathyPhase 2NCT01186250
Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation
A Phase 2 study testing Pioglitazone in people with Cardiac Allograft Vasculopathy, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to determine the benefit of using the FDA-approved insulin-sensitizing agent, Pioglitazone, on human heart transplant recipients. The objectives of this project are to (1) determine if pioglitazone effectively treats insulin resistance in heart transplant recipients, and (2) to determine… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Allograft Vasculopathy
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Dec 2013
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Heart transplant recipients, years 1-4 post-transplant
- Age >= 18 years
- Fasting TG/HDL ratio>=3.0 or Fasting TG>=150 mg/dL
Who cannot join
- Diabetes mellitus
- Severe liver dysfunction (ALT>=2.5 x upper limit of normal)
- Severe renal dysfunction (GFR<30 or Stage IV CKD)
- Moderate-severe fluid retention
- Clinical or echocardiographic signs of left ventricular dysfunction
- Contraindication to coronary angiography and/or IVUS
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
The purpose of this study is to determine the benefit of using the FDA-approved insulin-sensitizing agent, Pioglitazone, on human heart transplant recipients. The objectives of this project are to (1) determine if pioglitazone effectively treats insulin resistance in heart transplant recipients, and (2) to determine whether pioglitazone therapy after heart transplantation impacts the development or progression of cardiac allograft vasculopathy (CAV), a form of chronic rejection after heart transplantation.
Read the detailed description
CAV, a rapidly progressive obliterative disease involving the graft coronary arteries, is the leading cause of morbidity and mortality beyond the first year after heart transplantation. This common complication occurs in almost half of recipients within 3 years after heart transplantation, and is associated with high rates of graft failure and mortality. Clinical care of heart transplant recipients in the current era is greatly limited by the lack of effective treatment options to prevent or retard the progression of CAV. CAV appears to be strongly associated with the state of insulin resistance, which is present in over half of heart transplant recipients and is characterized by metabolic abnormalities including glucose intolerance, dyslipidemia, endothelial dysfunction, and high levels of circulating inflammatory markers. Insulin resistance can be effectively treated with pioglitazone, a TZD compound which directly affects tissue insulin sensitivity. In this study, we will enroll 32 insulin-resistant heart transplant recipients and will randomize them to pioglitazone or placebo for a one-year period. We will determine the efficacy of pioglitazone for the treatment of insulin resistance and prevention of the development and progression of CAV after heart transplantation. The data generated from this study will provide important preliminary data for future, larger-scale clinical investigations.
- Conditions
- Cardiac Allograft Vasculopathy
- Being tested
- Pioglitazone, Placebo
- Keywords
- cardiac allograft vasculopathy, pioglitazone, insulin resistance, heart transplant
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months
PlaceboDrug
placebo taken daily for one year
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | Pioglitazone Receives: Drug: Pioglitazone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Levels Area Under Curve(AUC)
Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.
Measured: Baseline and 1 year
Secondary outcomes (6)
Change in Intimal Volume
Intimal volume is defined as external elastic membrane volume minus lumen (luminal) volume measured at the heart Catheterization and intravascular Ultrasound( IVUS)
Measured: baseline and 1 year
Change in Levels of Fasting Glucose at Baseline and 1 Year
Oral Glucose Tolerance Test : blood was drawn for fasting plasma glucose and insulin levels, followed by ingestion of a solution containing 75grams of glucose. Repeat blood samples were collected for glucose and insulin levels at 30, 90, and 120 minutes after glucose ingestion. All glucose measurements were performed by the Clinical Translational Research Unit (CTRU) Stanford University.
Measured: Baseline and 1 year
Change From Baseline in TG/HDL Ratio at One Year
Triglyceride ratio to High Density Lipoprotien
Measured: Baseline and 1 year
Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)
The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery, the cross sections, predominantly in the left anterior descending coronary artery, from baseline to one-year follow-up, were studied. The IVUS cross sections were matched by using identifiable landmarks in the images, such as bifurcations or arterial calcification, or external landmarks, such as coronary veins or pericardium. In addition, the one-year IVUS studies were obtained with an angiographic roadmap of where the initial IVUS study was performed along the length of the vessel. The IVUS system auto pullback was performed at .5 mm/s from the mid-distal portion of the study vessel, where an easily identifiable landmark was visible (i.e., branchpoint). The following items were measured for each patient: maximal intimal thickness (MIT), intimal area (IA), and vessel area.
Measured: Baseline and 1 year
Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.
Competitive ELISA assay in Stanford laboratory.
Measured: Baseline and 1 year
Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year
measure of low levels of C-reactive protein to identify low but persistent levels of inflammation
Measured: Baseline and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2013
- Study completionDec 2013
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 Allograft VasculopathyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kiran Khush, Stanford University
- Investigators
- Kiran Khush, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01186250
- Sponsor's protocol ID
- SU-05282010-6202
- Other IDs
- CTRU protocol 1314, IRB protocol 19373
- Status last verified
- Jul 2016
- First submitted
- 19 Aug 2010
- Last updated
- 18 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation
- ClinicalTrials.gov ID
- NCT01186250
- Acronym / sponsor ID
- SU-05282010-6202
- Conditions
- Cardiac Allograft Vasculopathy
- Keywords
- cardiac allograft vasculopathy, pioglitazone, insulin resistance, heart transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 23 Aug 2010 (estimated)
- Results
- Posted 18 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the benefit of using the FDA-approved insulin-sensitizing agent, Pioglitazone, on human heart transplant recipients. The objectives of this project are to (1) determine if pioglitazone effectively treats insulin resistance in heart transplant recipients, and (2) to determine whether pioglitazone therapy after heart transplantation impacts the development or progression of cardiac allograft vasculopathy (CAV), a form of chronic rejection after heart transplantation.
Detailed description
CAV, a rapidly progressive obliterative disease involving the graft coronary arteries, is the leading cause of morbidity and mortality beyond the first year after heart transplantation. This common complication occurs in almost half of recipients within 3 years after heart transplantation, and is associated with high rates of graft failure and mortality. Clinical care of heart transplant recipients in the current era is greatly limited by the lack of effective treatment options to prevent or retard the progression of CAV. CAV appears to be strongly associated with the state of insulin resistance, which is present in over half of heart transplant recipients and is characterized by metabolic abnormalities including glucose intolerance, dyslipidemia, endothelial dysfunction, and high levels of circulating inflammatory markers. Insulin resistance can be effectively treated with pioglitazone, a TZD compound which directly affects tissue insulin sensitivity. In this study, we will enroll 32 insulin-resistant heart transplant recipients and will randomize them to pioglitazone or placebo for a one-year period. We will determine the efficacy of pioglitazone for the treatment of insulin resistance and prevention of the development and progression of CAV after heart transplantation. The data generated from this study will provide important preliminary data for future, larger-scale clinical investigations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: PioglitazonePioglitazone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Heart transplant recipients, years 1-4 post-transplant
- Age >= 18 years
- Fasting TG/HDL ratio>=3.0 or Fasting TG>=150 mg/dL
Key exclusion criteria (6 listed)
- Diabetes mellitus
- Severe liver dysfunction (ALT>=2.5 x upper limit of normal)
- Severe renal dysfunction (GFR<30 or Stage IV CKD)
- Moderate-severe fluid retention
- Clinical or echocardiographic signs of left ventricular dysfunction
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 |
|---|---|---|
| PioglitazoneAlso: Actos15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months | Drug | Pioglitazone |
| Placeboplacebo taken daily for one year | Drug | Placebo |
Primary outcome
Insulin Levels Area Under Curve(AUC)
Time frame: Baseline and 1 year
Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.
6 secondary outcomes
Change in Intimal Volume
Time frame: baseline and 1 year
Change in Levels of Fasting Glucose at Baseline and 1 Year
Time frame: Baseline and 1 year
Change From Baseline in TG/HDL Ratio at One Year
Time frame: Baseline and 1 year
Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)
Time frame: Baseline and 1 year
Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.
Time frame: Baseline and 1 year
Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year
Time frame: Baseline and 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kiran Khush principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone in people with Cardiac Allograft Vasculopathy, run by Stanford University 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 6 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: finished, as of the sponsor's last update on 18 Aug 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 phase mean?
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 18 Aug 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?
Insulin Levels Area Under Curve(AUC) (time frame: Baseline and 1 year). 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 18 Aug 2016.