Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03525379 |
| Other study ID # |
REV-HF-2015-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 26, 2017 |
| Est. completion date |
October 8, 2019 |
Study information
| Verified date |
May 2022 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a randomized, double-blind, placebo-controlled trial evaluating the effect of
resveratrol on metabolic and skeletal muscle function. Patients will be randomized and
allocated to either resveratrol or placebo, for 8 weeks with a 2-week run-in period before
the intervention period (to ensure they are not on any nutritional supplement that contains
resveratrol).
Description:
Trial Objectives Primary outcome- Change in Isolated Skeletal Muscle Blood Flow, Oxygen
Extraction and Consumption and Metabolic Rate of Recovery with Exercise by Cardiac MRI (CMR).
In order to evaluate potential changes in skeletal muscle vascular function and oxygen
extraction with resveratrol therapy, the investigators will use a lower limb (calf muscle)
targeted exercise protocol in conjunction with magnetic resonance imaging (MRI)32. MRI will
be used to measure, simultaneously, the peak rate of blood flow in the calf muscle along with
the whole calf muscle extraction of oxygen, which together are used to determine oxygen
consumption. This method allows the determinants of oxygen consumption (blood flow and oxygen
extraction) to be evaluated, which is necessary to understand the mechanisms of therapy
action.
Secondary outcomes-
1. Change in Vascular Function by CMR. Measurement of aortic distensibility will be used to
assess changes in the compliance of vascular system with therapy. Compliance will be
defined as the fractional change in cross-sectional area of the aorta over the cardiac
cycle (measured at both ascending and descending locations) divided by the corresponding
change in pressure (pulse pressure = systolic blood pressure - diastolic blood pressure,
measured with arm cuff at time of aorta imaging).
2. Change in Body Composition by CMR. Assessment of adipose and visceral fat content in
abdomen and skeletal muscle will be made using multi-echo DIXON magnetic resonance image
acquisition with automated fat/water decomposition using VARPO post-processing.
3. Phosphocreatinine (PCr) uptake/recovery on skeletal muscle by CMR. Skeletal muscle
metabolism will be measured on a 3T PRISMA MRI system (Peter S Allen MRI Centre)
equipped with a plantar-flexion exercise setup and phosphorous imaging capabilities.
Supine subjects will perform exercise (toe-push on one leg) until exhaustion. P NMR
spectra will be acquired continuously during exercise to measure PCr utilization, change
in muscle pH, and most importantly, the recovery rate following exercise. PCr recovery
following exercise is a direct measure of substrate utilization and oxygen supply, which
is measured as the rate of PCr replenishment. The rate constant (in seconds)
characterizes the exponential recovery of PCr to resting values (providing a
quantitative measure of oxidative phosphorylation. Normal values from healthy controls
are 30-35 seconds with prior studies of patients with HF show values of 76 seconds. A
study of reproducibility showed a coefficient of variability of 4.6% for this rate
constant (from repeated studies on separate days).
4. Change in LVEF, LVEDV and longitudinal strain by CMR. CMR remains the most precise
measure of cardiac structure and function and allows for very small sample sizes to
detect changes in important variables such as left ventricular ejection fraction (LVEF),
left ventricular end diastolic volume (LVEDV) and longitudinal strain. Longitudinal
strain is complimentary to volume and ejection fraction and is increasingly used to
detect subclinical changes in heart function even in cases of preserved ejection
fraction, and is predictive of HF outcomes. The investigators have reported a
coefficient of variability of 2.6% for measurement of ventricular volumes with MRI,
similar or better than previous studies, which would enable the measurement of a change
of 5 ml in LVEDV with therapy, for example, with only 10 subjects (α=0.05, power=0.95).
5. Distance walked on 6-minute walk test (6-MWT). The 6-MWT is a validated and reproducible
clinical endpoint that has been used to demonstrate differences in early phase work of
medications such as ACE inhibitors, cardiac resynchronization therapy, and exercise
interventions.
6. Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ has been used
for multiple large RCT and is sensitive to change, validated in patients with heart
failure and linked to prognosis in the short and long-term. A minimal clinically
important difference is 5 points.
7. Change in Functional Assessment of Chronic Illness Therapy (FACIT-F). The FACIT-F was
developed as a quality of life tool to evaluate small changes in fatigue for patients
undergoing anemia or cancer therapy. There are no other validated tools specific to
heart failure that address fatigue, despite the principal importance of this symptom.
Therefore, the FACIT-F will be used to measure fatigue.
8. Change in Sleep Quality. The Medical Outcomes Study (MOS) Sleep Scale is a
patient-reported, non-disease-specific instrument for evaluating sleep outcomes. The MOS
Sleep Scale measures subjective experiences of sleep across several different domains.
