The acute effect of beta-guanidinopropionic acid versus creatine or placebo in
healthy men (ABC Trial): study protocol for a randomized controlled trial.
Author(s): Karamat FA(1), Horjus DL(2), Haan YC(3), van der Woude L(4), Oudman I(5), van
Montfrans GA(6), Clark JF(7), Brewster LM(8,)(9,)(10).
Affiliation(s): Author information:
(1)Department of Vascular Medicine, Room F4-253, Academic Medical Center,
University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
f.a.karamat@amc.nl. (2)Department of Vascular Medicine, Room F4-253, Academic
Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the
Netherlands. d.l.horjus@amc.nl. (3)Department of Vascular Medicine, Room F4-253,
Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ,
Amsterdam, the Netherlands. y.c.haan@amc.nl. (4)Department of Vascular Medicine,
Room F4-253, Academic Medical Center, University of Amsterdam, Meibergdreef 9,
1105 AZ, Amsterdam, the Netherlands. l.vanderwoude@amc.nl. (5)Department of
Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam,
the Netherlands. i.oudman@amc.nl. (6)Department of Internal Medicine, Academic
Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
g.vanmontfrans@amc.nl. (7)Department of Neurology, Cincinnati Children's
Hospital, 3333 Burnet Ave, Cincinnati, Ohio, USA. joseph.clark@uc.edu.
(8)Department of Vascular Medicine, Room F4-253, Academic Medical Center,
University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
l.m.brewster@amc.nl. (9)Department of Internal Medicine, Academic Medical Center,
University of Amsterdam, Amsterdam, the Netherlands. l.m.brewster@amc.nl.
(10)Department of Social Medicine, Academic Medical Center, University of
Amsterdam, Amsterdam, the Netherlands. l.m.brewster@amc.nl.
Publication date & source: 2015, Trials. , 16:56
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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