Diabetes Mellitus, Type 2, Heart Failure, Diastolic
Conditions
Keywords
Diabetes, Diastolic Heart Failure, Aortic Stiffness, Exenatide
Brief summary
People with type 2 diabetes experience heart failure more often than do people without diabetes. This may be due to increased stiffness in the heart as a result of diabetes. This study will examine whether exenatide, a medication used to treat diabetes, may have beneficial effects on the heart in people with type 2 diabetes and heart failure.
Detailed description
Diastolic heart failure is a life-threatening condition that occurs when the ventricles of the heart become stiff and do not fully relax, preventing the heart from properly filling with blood. The circulation of blood then backs up, and blood collects in the body's organs, primarily the lungs. However, people with diastolic heart failure may have a normal ejection fraction, which is a measure of the amount of blood that the heart pumps out with each heart beat. Having type 2 diabetes may increase the risk of diastolic heart failure. Also, people with both heart failure and type 2 diabetes are more likely to experience poor health and even death than are people with only heart failure. It is possible that diabetes leads to increased stiffness of the ventricles and the aorta, which is the main blood vessel into which the heart empties. Exenatide, part of a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists, is a new medication that is currently used to treat elevated blood sugar levels in people with diabetes. Some studies have shown that this class of medications may have a positive effect on the heart and blood vessels. The purpose of this study is to determine the effect that exenatide has on aortic and left ventricular stiffness in people who have type 2 diabetes and diastolic heart failure. This 12-week study will enroll adults with type 2 diabetes and diastolic heart failure with normal ejection fraction. At a baseline study visit, participants will undergo a physical examination, blood pressure and heart rate measurements, a blood collection, an echocardiogram to obtain images of the heart, and a non-invasive test that measures blood flow in the aorta. Participants will then be randomly assigned to receive either exenatide or usual care. Participants who receive exenatide will inject the medicine twice a day for 12 weeks. At Week 4, these participants will attend a study visit to adjust the medication dosage and to report any problems, and at Week 6, study staff will follow up with participants by phone. All participants will attend a study visit at Week 12 for repeat baseline testing.
Interventions
DRUGExenatide
5 μg of exenatide subcutaneously twice a day for 4 weeks, followed by 10 μg of exenatide subcutaneously twice a day for an additional 8 weeks
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable New York Heart Association (NYHA) Class II-IV heart failure symptoms for at least 4 weeks before study entry * Diagnosis of diastolic heart failure with a normal ejection fraction * Admitted to the hospital with a diagnosis of heart failure in the 12 months before study entry * Type 2 diabetes
Exclusion criteria
* Unstable angina, heart attack, coronary artery bypass surgery, or angioplasty in the 3 months before study entry * Angina with exertion * Technically inadequate echocardiogram * Atrial fibrillation or atrial flutter * Severe valvular heart disease * Significant kidney insufficiency (serum creatinine greater than 2.0 mg/dL or require hemodialysis) * Conditions that may be associated with changes in markers of fibrosis or collagen turnover (e.g., ongoing or active rheumatological disease, requiring significant anti-inflammatory agents, immunosuppression, pulmonary fibrosis, active cancer) * Significant history of active substance abuse * Type 1 diabetes * Type 2 diabetes requiring chronic insulin use before study entry * Active thiazolidinedione (TZD) use, because TZDs have been shown to worsen volume retention and may exacerbate signs and/or symptoms of heart failure * Pregnant or breastfeeding * Hypertrophic cardiomyopathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity | Measured at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Left Ventricular Diastolic Stiffness, Serum Levels of Advanced Glycation End Products, Serum Biomarkers of Collagen Synthesis, and Serum Levels of Brain Natriuretic Peptide | Measured at Week 12 | Given the cessation of trials, the biomarkers analyses and diastolic function measures were not performed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Participants will receive usual care for 12 weeks. The care will be dictated by the primary physician and/or diabetologist caring for the participant. Efforts will be made to ensure that all participants receive standard measures as indicated by guidelines, with a particular emphasis on blood pressure control and glucose control. | 1 |
| Exenatide Participants will receive exenatide for 12 weeks.
Exenatide: 5 μg of exenatide subcutaneously twice a day for 4 weeks, followed by 10 μg of exenatide subcutaneously twice a day for an additional 8 weeks | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Usual Care | Exenatide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity
Time frame: Measured at Week 12
Population: For the usual care, data were obtained for only person, but data was collected only at baseline and follow-up data were not collected. For the exenatide arm, data were collected for only one participant at baseline and follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual Care | Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity | Baseline Pulse Wave Velocity | 11.4 m/sec | Standard Deviation 0 |
| Usual Care | Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity | Follow-up Pulse Wave Velocity | NA m/sec | — |
| Exenatide | Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity | Baseline Pulse Wave Velocity | 9.3 m/sec | Standard Deviation 0 |
| Exenatide | Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity | Follow-up Pulse Wave Velocity | 10.2 m/sec | Standard Deviation 0 |
Secondary
Changes in Left Ventricular Diastolic Stiffness, Serum Levels of Advanced Glycation End Products, Serum Biomarkers of Collagen Synthesis, and Serum Levels of Brain Natriuretic Peptide
Given the cessation of trials, the biomarkers analyses and diastolic function measures were not performed.
Time frame: Measured at Week 12
Population: Given the cessation of trials, the biomarkers analyses and diastolic function measures were not performed.