Congestive Heart FailurePhase 2NCT00064727
Rosiglitazone to Treat Patients With Heart Failure and Glucose Intolerance or Type II Diabetes
A Phase 2 study testing Avandia (Rosiglitazone) and Avanclia (Rosiqlitazone) in people with Congestive Heart Failure, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial summary
This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Read more about this study
- Who is it for?
- Ages 22 years and olderHealthy volunteers can take part
- Conditions the study is for
- Congestive Heart Failure
- What is being tested?
- Avandia (Rosiglitazone) and Avanclia (Rosiqlitazone)
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Jul 2003to 11 Apr 2007
- Phase
- Phase 2
- 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 22 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult normal volunteers, age matched (55-75 years of age)
- Adult patients greater than 21 years of age who meet the following criteria:
- Heart Failure due to ischemic heart disease or of idiopathic etiology
- Depressed LV systolic function, EF less than or equal to 0.45 by Radionuclide Angiography (MUGA)
- New York Heart Association Functional Class II or III
- Patient stable on current heart failure therapy
- Evidence of insulin resistance or type II diabetes on insulin-sensitivity screening
- No predicted cardiac revascularization therapy requirements
Who cannot join
- Pregnant or lactating
- History of admission for acute heart failure exacerbation within last one month
- Acute myocardial infarction within the last three months
- Cardiac resynchronization pacemaker placement within the last three months
- Genetic defect known to have induced heart failure
- Serum creatinine greater than 2.5 mg/dL.
Show all 15Show fewer
- Liver transaminase levels greater than 2.5 x upper limit of normal
- Requirement for insulin therapy to control blood glucose
- Current use of thiazolidinedione for diabetic control or history of discontinuation of thiazolidinedione therapy following development of side effects
- Uncontrolled blood glucose levels or the use of insulin therapy to control diabetes
- Immune compromise including chronic HIV, HBV, and HCV infection
- Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease
- Participation in unrelated research involving investigational pharmacological agent 30 days before planned dosing
- Current alcohol or drug abuse
- Inability to provide informed consent
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Suburban Hospital
Bethesda, Maryland, 20814
National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Attenuating Insulin Resistance as a Therapeutic Target in the Management of Heart Failure
This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Because of a lowered sensitivity to the hormone insulin, patients with type II diabetes or glucose-intolerance do not regulate glucose (sugar) effectively. Rosiglitazone is used to treat type II diabetes, but it is not commonly given to patients with heart failure because it can cause leg swelling and, rarely, pulmonary edema. However, patients with heart failure who also have glucose intolerance or type II diabetes generally fare worse than those with heart failure alone, and therapies that decrease insulin resistance may be beneficial to these patients.
Patients 21 years of age and older with heart failure and type II diabetes or glucose intolerance, or both, may be eligible for this study. Patients must be stable on current therapy for heart failure and must not have any planned surgeries for coronary artery disease. Candidates will be admitted to the NIH Clinical Center for from 2 to 7 days for screening procedures, which include a medical history and physical examination, blood and urine tests, electrocardiogram (ECG), chest x-ray, magnetic resonance imaging (MRI), exercise testing, and echocardiography (ultrasound test of the heart).
Read more
Participants will be randomly assigned to receive either rosiglitazone or placebo (an identical-looking pill with no active ingredient). They will take one tablet a day for the first month, one tablet twice a day for the second month, and then two tablets twice a day from the third month to the end of the study at 6 months. During the treatment period, patients will have a history, physical examination, and blood tests every 4 weeks, exercise testing and echocardiography at 3 and 6 months, and urinalysis, electrocardiogram and MRI at 6 months. To check for fluid accumulation in the legs or lungs, patients will report their weight and symptoms every 2 weeks throughout the study. After the 6-month treatment period, patients will be put back on the diabetes medicines they were taking before the study. Their physicians will be notified of possible modifications in treatment for maintaining optimum glucose tolerance.
Six months after completing treatment (one year after beginning the study), patients will return to the Clinical Center for blood tests to measure the long-term effects of rosiglitazone and to evaluate progress. They will then be invited to return to the clinic for annual checkups, if possible, or for yearly follow-up by mail or telephone to review their health status.
Read the detailed description
The current medical management for heart failure invariably employs a 'one treatment fits all' approach. The failure to appreciate specific genotypic/phenotypic features in heart failure subjects is postulated to be a reason recent heart failure studies evaluating the efficacy of tumor necrosis factor alpha antagonists and endothelin receptor blockers showed no overall benefit. This experience suggests that the future improvement in the medical management of patients with heart failure may require pre-prescription genotyping/phenotyping to tailor drug therapy to the underlying mechanistic processes orchestrating the development and progression of heart failure.
In this regard, the insulin-resistance syndrome has been recognized as a significant associated factor with the development of cardiac hypertrophy and heart failure. A novel class of agents has been developed that increase insulin sensitivity via the activation of the transcription factor-peroxisomal proliferators activated receptor gamma (PPAR gamma). These drugs, known as the thiazolidinediones are currently licensed for the treatment of type II diabetes mellitus. Interestingly, at the preclinical level, PPAR gamma appears to play a regulatory role in attenuating the development of cardiac hypertrophy and thiazolidinedione therapy has been shown to attenuate the development of contractile dysfunction in mice following myocardial infarction.
The hypothesis intrinsic to this proposal is that insulin resistance is commonly associated with the development/progression of heart failure and that improving insulin sensitivity will be of clinical benefit in this select group of patients with heart failure. The primary objective of this study is to establish the safety and efficacy of thiazolidinedione therapy in insulin-resistant heart failure subjects. The study is designed as a phase II, randomized, double-blind, placebo-controlled dose escalation study. The primary outcomes will be the safety of administration, and the evaluation of the modulation in contractile function in heart failure subjects treated with thiazolidnediones. Moreover, changes in functional capacity and the determination of the biochemical and genomic modification of heart failure and insulin-resistance will be measured in response to thiazolidnedione therapy in heart failure subjects.
- Conditions
- Congestive Heart Failure
- Being tested
- Avandia (Rosiglitazone), Avanclia (Rosiqlitazone)
- Keywords
- Ventricular Contractile Function, Diastolic Dysfunction, PPAR gamma, Gene Expression Patterns, Insulin Sensitization, Glucose Intolerance, Intolerance
- Medical subject headings
- Heart Failure, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avandia (Rosiglitazone)Drug
Avanclia (Rosiqlitazone)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2003 (estimated)
- Study start9 Jul 2003
- Study completion11 Apr 2007
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 Congestive Heart FailureStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00064727
- Sponsor's protocol ID
- 030217
- Other IDs
- 03-H-0217
- Status last verified
- 11 Apr 2007
- First submitted
- 10 Jul 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Coats AJ. Angiotensin type-1 receptor blockers in heart failure. Prog Cardiovasc Dis. 2002 Jan-Feb;44(4):231-42. doi: 10.1053/pcad.2002.31585.
PubMed 12007079
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Attenuating Insulin Resistance as a Therapeutic Target in the Management of Heart Failure
- ClinicalTrials.gov ID
- NCT00064727
- Acronym / sponsor ID
- 030217
- Conditions
- Congestive Heart Failure
- Keywords
- Ventricular Contractile Function, Diastolic Dysfunction, PPAR gamma, Gene Expression Patterns, Insulin Sensitization, Glucose Intolerance, Intolerance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 9 Jul 2003
- Study completion
- 11 Apr 2007
- First posted
- 11 Jul 2003 (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.
This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Because of a lowered sensitivity to the hormone insulin, patients with type II diabetes or glucose-intolerance do not regulate glucose (sugar) effectively. Rosiglitazone is used to treat type II diabetes, but it is not commonly given to patients with heart failure because it can cause leg swelling and, rarely, pulmonary edema. However, patients with heart failure who also have glucose intolerance or type II diabetes generally fare worse than those with heart failure alone, and therapies that decrease insulin resistance may be beneficial to these patients.
Patients 21 years of age and older with heart failure and type II diabetes or glucose intolerance, or both, may be eligible for this study. Patients must be stable on current therapy for heart failure and must not have any planned surgeries for coronary artery disease. Candidates will be admitted to the NIH Clinical Center for from 2 to 7 days for screening procedures, which include a medical history and physical examination, blood and urine tests, electrocardiogram (ECG), chest x-ray, magnetic resonance imaging (MRI), exercise testing, and echocardiography (ultrasound test of the heart).
Participants will be randomly assigned to receive either rosiglitazone or placebo (an identical-looking pill with no active ingredient). They will take one tablet a day for the first month, one tablet twice a day for the second month, and then two tablets twice a day from the third month to the end of the study at 6 months. During the treatment period, patients will have a history, physical examination, and blood tests every 4 weeks, exercise testing and echocardiography at 3 and 6 months, and urinalysis, electrocardiogram and MRI at 6 months. To check for fluid accumulation in the legs or lungs, patients will report their weight and symptoms every 2 weeks throughout the study. After the 6-month treatment period, patients will be put back on the diabetes medicines they were taking before the study. Their physicians will be notified of possible modifications in treatment for maintaining optimum glucose tolerance.
Six months after completing treatment (one year after beginning the study), patients will return to the Clinical Center for blood tests to measure the long-term effects of rosiglitazone and to evaluate progress. They will then be invited to return to the clinic for annual checkups, if possible, or for yearly follow-up by mail or telephone to review their health status.
Detailed description
The current medical management for heart failure invariably employs a 'one treatment fits all' approach. The failure to appreciate specific genotypic/phenotypic features in heart failure subjects is postulated to be a reason recent heart failure studies evaluating the efficacy of tumor necrosis factor alpha antagonists and endothelin receptor blockers showed no overall benefit. This experience suggests that the future improvement in the medical management of patients with heart failure may require pre-prescription genotyping/phenotyping to tailor drug therapy to the underlying mechanistic processes orchestrating the development and progression of heart failure.
In this regard, the insulin-resistance syndrome has been recognized as a significant associated factor with the development of cardiac hypertrophy and heart failure. A novel class of agents has been developed that increase insulin sensitivity via the activation of the transcription factor-peroxisomal proliferators activated receptor gamma (PPAR gamma). These drugs, known as the thiazolidinediones are currently licensed for the treatment of type II diabetes mellitus. Interestingly, at the preclinical level, PPAR gamma appears to play a regulatory role in attenuating the development of cardiac hypertrophy and thiazolidinedione therapy has been shown to attenuate the development of contractile dysfunction in mice following myocardial infarction.
The hypothesis intrinsic to this proposal is that insulin resistance is commonly associated with the development/progression of heart failure and that improving insulin sensitivity will be of clinical benefit in this select group of patients with heart failure. The primary objective of this study is to establish the safety and efficacy of thiazolidinedione therapy in insulin-resistant heart failure subjects. The study is designed as a phase II, randomized, double-blind, placebo-controlled dose escalation study. The primary outcomes will be the safety of administration, and the evaluation of the modulation in contractile function in heart failure subjects treated with thiazolidnediones. Moreover, changes in functional capacity and the determination of the biochemical and genomic modification of heart failure and insulin-resistance will be measured in response to thiazolidnedione therapy in heart failure subjects.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult normal volunteers, age matched (55-75 years of age)
- Heart Failure due to ischemic heart disease or of idiopathic etiology
- Depressed LV systolic function, EF less than or equal to 0.45 by Radionuclide Angiography (MUGA)
- New York Heart Association Functional Class II or III
- Patient stable on current heart failure therapy
Key exclusion criteria (15 listed)
- Pregnant or lactating
- History of admission for acute heart failure exacerbation within last one month
- Acute myocardial infarction within the last three months
- Cardiac resynchronization pacemaker placement within the last three months
- Genetic defect known to have induced heart failure
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 |
|---|---|---|
| Avandia (Rosiglitazone) | Drug | – |
| Avanclia (Rosiqlitazone) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 12007079Coats AJ. Angiotensin type-1 receptor blockers in heart failure. Prog Cardiovasc Dis. 2002 Jan-Feb;44(4):231-42. doi: 10.1053/pcad.2002.31585.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avandia (Rosiglitazone) and Avanclia (Rosiqlitazone) in people with Congestive Heart Failure, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites 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 8 inclusion and 15 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00064727, 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 2 Jul 2017.