Diabetes Complications, Type II Diabetes Mellitus
Conditions
Keywords
Diabetes, Diabetic Cardiomyopathy, Triglycerides
Brief summary
This study will test whether lowering the delivery of excess fats to the heart in persons with type-2 diabetes mellitus improves heart muscle function. The investigators will also test whether specific lipid molecular species in plasma can serve as biomarkers for diabetic heart disease.
Detailed description
Screening procedures include 12-hour fasting blood draw, urine pregnancy testing for females, completion of medical history questionnaire, and stress echocardiography to rule out coronary artery disease or cardiomyopathy. Subjects who meet screening criteria will return for visit 2, which consists of a urine collection, 12-hour fasting blood draw, dual-energy X-ray absorptiometry (DXA) for body composition, magnetic resonance spectroscopy analysis of the liver, and resting echocardiogram for analysis of heart structure and function. Subjects will then be randomized to treatment with fenofibrate (160 mg/d) or an identical-appearing placebo for 12 weeks. They will be asked to continue their usual medications, diet and physical activity. Subjects will receive a pedometer to wear daily to track their physical activity. Subjects will meet with dietitians from the Lifestyle Intervention Core to complete a 24-hour dietary recall. They will be instructed to record their daily blood glucose concentrations, distance walked and any side effects, illnesses or stresses in a study-supplied log. Subjects will be instructed to either email or fax the log to the study coordinator each week (or discuss by phone). Subjects will return 6 weeks after starting intervention for visit 3 to ensure their medical safety. Procedures at this visit include an interim medical history, urine pregnancy test for females, blood draw to rule out untoward effects of the study drug on liver or kidney function, pill count to assess compliance, review of logs of blood glucose, distance walked, and side effects, illnesses or stresses, and meeting with a dietitian for a 24-hour dietary recall. Subjects will continue to take their study medication/placebo and keep logs of blood glucose levels, distance walked, and side effects, illnesses and stresses for another 6 weeks. They will return for visit 4 after 12 total weeks of intervention. Visit 4 involves a urine collection, 12-hour fasting blood draw, review of subject logs, pill count, and 24-hour dietary recall. In addition, magnetic resonance spectroscopy analysis of the liver and resting echocardiogram analysis of the heart will be performed to determine if there have been any changes in liver fat or heart function during the 12-week intervention.
Interventions
DRUGFenofibrate
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Leducq Foundation
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus
Exclusion criteria
* body weight \> 300 lb. * HIV * hypothyroid * steroid medication, fenofibrate * smoking * BP \> 140/90 * heart disease * pregnant or lactating * consumption of \> 5 alcoholic drinks/wk * creatinine \> 1.5 mg/dL * hematocrit \< 28
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cardiac Diastolic Function as Measured by E' (cm/s) | Baseline and 12 weeks | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. |
| Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | Baseline and 12 weeks | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in C24:0/C16:0 Ceramide Ratio | Baseline and 12 weeks | Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from clinics, practices and laboratories within the Barnes-Jewish Hospital consortium, Volunteer for Health and Diabetes Research Connections recruitment programs at Washington University School of Medicine, and through local advertisements, posters, emails and flyers. Dates of recruitment were from May 2013 to October 2017.
Pre-assignment details
Potential subjects were given the approved consent form to consider. If interested, they were scheduled for a screening visit in the Center for Applied Research Sciences. The consent form was signed before any testing took place. Blood and urine were collected and a cardiac stress test was performed to evaluate the subject for eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Fenofibrate One fenofibrate 160 mg capsule per day for 12 weeks
Fenofibrate | 34 |
| Placebo for Fenofibrate One inert sugar pill per day for 12 weeks
Placebo for fenofibrate | 36 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo for Fenofibrate | Fenofibrate |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 8.2 | 54.6 years STANDARD_DEVIATION 8.3 | 54.2 years STANDARD_DEVIATION 8.2 |
| C24:0/C16:0 ceramides | 11.8 ratio STANDARD_DEVIATION 2.8 | 12.4 ratio STANDARD_DEVIATION 3 | 11.2 ratio STANDARD_DEVIATION 2.4 |
| Cardiac Diastolic Function (E') | 8.1 cm/s STANDARD_DEVIATION 1.7 | 7.99 cm/s STANDARD_DEVIATION 1.78 | 8.30 cm/s STANDARD_DEVIATION 1.7 |
| Cardiac Systolic Function (Fractional Shortening) | 38.2 percent STANDARD_DEVIATION 6.7 | 38 percent STANDARD_DEVIATION 6 | 39 percent STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 33 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 53 Participants | 26 Participants | 27 Participants |
| Region of Enrollment United States | 70 participants | 36 participants | 34 participants |
| Sex: Female, Male Female | 48 Participants | 24 Participants | 24 Participants |
| Sex: Female, Male Male | 22 Participants | 12 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 36 |
| other Total, other adverse events | 2 / 34 | 0 / 36 |
| serious Total, serious adverse events | 0 / 34 | 0 / 36 |
Outcome results
Primary
Change in Cardiac Diastolic Function as Measured by E' (cm/s)
Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline.
Time frame: Baseline and 12 weeks
Population: All participants for whom E' (diastolic function) was measured at baseline and 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate | Change in Cardiac Diastolic Function as Measured by E' (cm/s) | -0.02 cm/s | Standard Deviation 1.35 |
| Placebo for Fenofibrate | Change in Cardiac Diastolic Function as Measured by E' (cm/s) | 0.55 cm/s | Standard Deviation 1.58 |
Comparison: Null hypothesis is no difference of mean change of cardiac diastolic function as measured by E' (cm/s) between placebo and Fenofibrate.p-value: 0.0795% CI: [-1.56, 0.04]ANCOVA
Primary
Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent
Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline.
Time frame: Baseline and 12 weeks
Population: All participants for whom fractional shortening was measured at baseline and 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate | Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | 0.025 percent | Standard Deviation 0.09 |
| Placebo for Fenofibrate | Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | 0.030 percent | Standard Deviation 0.083 |
Comparison: Null hypothesis is no difference of mean change of fractional shortening percent between placebo and Fenofibrate.p-value: 0.812895% CI: [-0.0418, 0.0543]ANCOVA
Secondary
Change in C24:0/C16:0 Ceramide Ratio
Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma.
Time frame: Baseline and 12 weeks
Population: All participants for whom C24:0 and C16:0 ceramides were measured at baseline and 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate | Change in C24:0/C16:0 Ceramide Ratio | -1.6 ratio | Standard Deviation 1.66 |
| Placebo for Fenofibrate | Change in C24:0/C16:0 Ceramide Ratio | -0.03 ratio | Standard Deviation 2.44 |
Comparison: Null hypothesis is no difference of mean change of C24:0/C16:0 ceramide ratio between placebo and Fenofibrate.p-value: 0.003495% CI: [-2.93, -0.65]ANCOVA