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01.12.2015 | Study protocol | Ausgabe 1/2015 Open Access

Trials 1/2015

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial

Zeitschrift:
Trials > Ausgabe 1/2015
Autoren:
Fares A Karamat, Deborah L Horjus, Yentl C Haan, Lisa van der Woude, Inge Oudman, Gert A van Montfrans, Joseph F Clark, Lizzy M Brewster
Wichtige Hinweise

Competing interests

L.B. is an inventor on NL patent WO/2012/138226 (filed).

Authors’ contributions

FK participated in the design of the study, drafted the manuscript, and will conduct the clinical studies and the primary statistical analysis. DH participated in the design of the study, drafted the manuscript, and will conduct the clinical studies and the primary statistical analysis. YH participated in the design of the study, drafted the manuscript, and will conduct the clinical studies and the primary statistical analysis. LW participated in the design of the study, and will conduct the clinical studies. IO initiated the study design, drafted the manuscript, and will supervise the clinical studies. GM participated in the design of the study and will supervise the clinical studies. JC participated in the design of the study. LB, the grant holder, conceived the study, initiated the study design, provided statistical expertise in the clinical trial design, will supervise the clinical studies, and conduct and supervise the statistical analyses. All authors contributed to the writing of the study protocol, and read and approved the final manuscript.

Abstract

Background

Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo.

Methods/Design

This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance.

Discussion

There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs.

Trial registration

The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444), registered 9 March 2014.
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