Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose

Janet D Pierce, Diane E Mahoney, John B Hiebert, Amanda R Thimmesch, Francisco J Diaz, Carol Smith, Qiuhua Shen, Dinesh Pal Mudaranthakam, Richard L Clancy, Janet D Pierce, Diane E Mahoney, John B Hiebert, Amanda R Thimmesch, Francisco J Diaz, Carol Smith, Qiuhua Shen, Dinesh Pal Mudaranthakam, Richard L Clancy

Abstract

Background: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF.

Methods: Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics).

Discussions: Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance.

Trial registration: ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

Keywords: Bioenergetics; D-ribose; Heart failure with preserved ejection fraction (HFpEF); ubiquinol.

Conflict of interest statement

Ethics approval and consent to participate

The University of Kansas Medical Center IRB has reviewed and approved implementation of this study. The PI and research staff including Project Director and Research Associate will participate in recruitment of subjects (patients with diastolic heart failure, or HFpEF). Patients with HFpEF will be asked for permission to be contacted, have the study explained, be invited to participate, and be provided written informed consent. The potential subjects will be informed that the purpose of the study is to examine the effects of oral ubiquinol, D-ribose, or a combination of the two in treating patients with HFpEF. Consent forms will be given to all subjects and their signatures will be obtained and witnessed, if they agree to participate. The consent forms will include a description of the study, nature of the data collection, the potential benefits and adverse reactions anticipated, and the methods used to ensure confidentiality. The standard care of subjects will not be changed, withdrawn, or reduced for any subject in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study groups and Number of Subjects per Group
Fig. 2
Fig. 2
Study design and groups

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