Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03133793 |
| Other study ID # |
STUDY00140741 |
| Secondary ID |
5R01AG054486-02 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
February 5, 2018 |
| Est. completion date |
March 12, 2021 |
Study information
| Verified date |
March 2022 |
| Source |
University of Kansas Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to compare the clinical benefits of CoQ10 and D-ribose taken by
patients who have diastolic heart failure, or heart failure with preserved ejection fraction
(HFpEF).
Description:
This study used a novel design to compare ubiquinol and/or D-ribose as supplemental
treatments for HFpEF using a biobehavioral model. This was a randomized, double-blind,
controlled trial with a total sample size of (N) = 216 All participants received usual care
for HFpEF. Efforts were made to recruit 50% females which is the actual proportion of HFpEF
patients in Kansas City area. There were 63 subjects that did not make the 7 day enrollment
which dropped our participants to 153.
Participants in this study were randomized into 4 study groups (total n = 153):
N1 = 39 subjects: Control, receive no ubiquinol and no D-ribose; placebo capsules & powder
per day.
N2 = 39 subjects: Ubiquinol group, receive 600 mg of ubiquinol/day, D-ribose placebo powder
per day.
N3 = 37 subjects: D-ribose group, receive 15 g of D-ribose/day, placebo capsules for
ubiquinol per day.
N4 = 38 subjects: Ubiquinol + D-ribose group, receive 600 mg ubiquinol and 15 g D-ribose per
day.
The enrolled patients were randomized into four groups to receive ubiquinol (600 mg daily),
D-ribose (15 g daily), ubiquinol plus D-ribose, or placebo for a period lasting 12 weeks.
Both the ubiquinol and the D-ribose supplements used in the study had a certificate of
analysis from the manufacturer. The Project Manager reviewed the electronic health records at
the University of Kansas Health System (TUKHS) to identify subjects that met the study
criteria and were approached to study inclusion. Once the subject signed the informed consent
and successfully completed the 7-day run-in, they were randomly assigned to one of the four
groups using a list created by a computer-based random number generator. All supplements and
the placebo were indistinguishable in packaging and were distributed by the Project Manager
or Research Associate independent of the PI so that the allocation of subjects to a treatment
or placebo group were concealed from both subjects and key research personnel.
All subjects arrived at the Clinical and Translational Science Unit (CTSU) and escorted to a
private exam room. They completed the demographic form at baseline. The KCCQ and Vigor scale
from the Profile of Mood States (POMS) were completed in CTSU visits at baseline, and 12
weeks along with the subject's blood pressure, heart rate, height, and weight. The patient
was given privacy and asked to remove clothing above the waist. A disposable gown was
provided, and the patient laid supine on the bed while an echocardiogram was completed.
Approximately, 1 ml of blood was drawn to measure lactate. adenosine triphosphate (ATP), and
B-type natriuretic peptide (BNP). The blood samples were measured with point-of-contact
instruments within 5 minutes at the CTSU. After the echocardiogram, questionnaires, BNP, and
ATP measurements, the subjects completed the six-minute walk test (6MWT) with the Borg scale.
The entire data collection period was approximately 2 hours for each subject's visit to the
CTSU. Follow-up calls occurred at 3, 6, and 9 weeks during the trial.
Various cardiovascular risk factors were recorded such as tobacco usage, diabetes mellitus,
hypercholesterolemia, hypertension, and family history of cardiovascular disease. Smoking
status was recorded as either smoker or non-smoker. Diabetes mellitus was also determined by
a history of the disease or use of medication for diabetes. Hypercholesterolemia was defined
as a fasting total serum cholesterol level ≥ 4.9 mmol/l or use of medication. Hypertension
was defined as either systolic or diastolic blood pressure ≥ 140/90 mmHg or use of
hypertensive medications.
Aims and Hypotheses.
There were 2 aims and 6 hypotheses:
AIM #1: To determine the effects of oral ubiquinol, D-ribose, or a combination of the two
administered during 12 weeks on symptoms accompanying low bioenergetics in patients with
HFpEF.
Hypothesis #1. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will enhance the health status of patients with HFpEF as measured by the Kansas City
Cardiomyopathy Questionnaire (KCCQ).
Primary outcomes of the study were patient-centered; thus the measurement of health status
was a priority. Bioenergetics has both biological and behavioral components. The biological
component (i.e., improved heart function) and its measurement was discussed in Aim #2.
Investigators assessed patients' perceptions of their symptoms using the KCCQ, a
self-administered questionnaire that measures patients' perceptions of five domains of their
health status relevant to HFpEF. These domains are: (1) physical limitations, (2) symptoms,
(3) self-efficacy, (4) quality of life, and (5) social interference. The KCCQ consists of 24
items to which patients respond on a scale indicating limitations due to HF. For example, for
activities such as dressing, doing yard work, or climbing a flight of stairs, patients were
asked to check a response that indicates the degree to which HF has limited their ability:
"Extremely Limited," "Quite a bit Limited," "Moderately Limited," "Slightly Limited," "Not at
all Limited," or "Limited for other reasons or did not do the activity." Another item is:
"Over the past 2 weeks, how many times has shortness of breath limited your ability to do
what you wanted?" Response alternatives are: "All of the time," "Several times," "At least
once a day," "3 or more times per week but not every day," "1-2 times per week," "Less than
once a week," and "Never over the past 2 weeks." The KCCQ takes only 4 to 6 minutes to
complete and has been used in more than a hundred studies. It has excellent psychometric
properties and clinical usefulness including: (1) high test-retest reliability; (2) high
internal consistency within each area (e.g., Cronbach's alpha ranged from 0.78 to 0.90); (3)
patients' scores concerning their health status correlate well with objective measurements of
their functional capacities; and (4) the scale's sensitivity for detecting clinical changes
in HF patients is significantly greater than that of the Minnesota Living with Heart Failure
Scale. Investigators used the KCCQ to compare the changes in health status of patients with
HFpEF taking ubiquinol, D-ribose, ubiquinol + D-ribose, or placebo.
Hypothesis #2. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will increase the level of vigor in patients with HFpEF as measured by the Vigor subscale of
the Profile of Mood States (POMS).
Using the Vigor subscale from the POMS questionnaire, patients rated themselves on eight
adjectives (lively, active, energetic, cheerful, alert, full of pep, carefree, and vigorous)
on a five-point scale (0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit, and 4 =
extremely). The Vigor scale has very high internal consistency (Cronbach's alpha = 0.90), and
it takes only 1 minute to complete. In many studies it has been found to be effective for
assessing vigor changes associated with exercise. The KCCQ and POMS Vigor scale were
administered to patients after they have been sitting quietly for 10 minutes at the beginning
of each visit (baseline, 12 weeks). The total time for patients to complete both
questionnaires was 5 to10 minutes.
AIM #2: To determine the effects of oral ubiquinol, D-ribose, or a combination of the two
over 12 weeks on biological measures in patients with HFpEF.
Hypothesis #3. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will improve left ventricular diastolic function measured by advanced echocardiographic
imaging in patients with HFpEF.
Two-dimensional Doppler echocardiography was used for myocardial imaging to assess cardiac
function in patients with HFpEF. In this study, a echocardiography technician performed the
echocardiograms during each visit (baseline and 12 weeks). Dr. Hiebert (cardiologists)
determine ejection fraction (EF) and the ratio of mitral peak velocity of early filling (E)
to early diastolic mitral annular velocity (eꞌ) (E/eꞌ ratio) (SV, EDV, EF) from the
echocardiogram.
Hypothesis #4. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will increase the distance that patients with HFpEF can walk in 6 minutes.
Investigators examined the effects of ubiquinol and/or D-ribose on the 6MWT at baseline and
12 weeks. Participants were asked to wear appropriate clothes and shoes and walk the longest
distance possible in 6 minutes. Prior to exercising, there was a 10-minute rest period during
which heart rate and blood pressure were recorded. Subjects walked indoors on a flat,
straight 30-meter path marked every 3 meters, and they were informed that they could slow
down or stop at any time. A one-lap demonstration was completed before the test began. The
distance walked was recorded. Following the 6MWT, a 0.5 ml blood sample was obtained for
lactate measurement. Lactate provides a measure of the oxygen debt occurring during exercise
and correlates directly with reported dyspnea and fatigue. The patient also recorded
perceived dyspnea and fatigue at baseline and at the end of each walk by using the Borg
scale, where 0 = nothing at all, 5 = severe, and 10 = very severe.
Hypothesis #5. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will decrease venous blood B-type natriuretic peptide (BNP) levels in patients with HFpEF.
BNP concentration was measured using a portable i-STAT handheld analyzer. A blood sample (20
μl) was obtained from a finger stick after the subjects have completed the questionnaires at
baseline and 12 weeks. Investigators measured BNP concentration at each visit.
Hypothesis #6. Ubiquinol (600 mg daily), D-ribose (15 g daily), or a combination of the two
will decrease the lactate/ATP ratio in patients with HFpEF.
0.1 ml blood sample obtained by finger stick was used for ATP measurements (AquaSnap Total
system) after the subject had completed the questionnaires and echocardiograms. Lactate
concentration was measured after the 6MWT with a portable i-STAT handheld instrument and
requires 0.5 ml blood.
