The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC-Trial): A randomized controlled first-in-human trial
Karamat FA, Horjus DL, Haan YC, van der Woude L, Schaap MC, Oudman I, van Montfrans GA, Nieuwland R, Salomons GS, Clark JF, Brewster LM
British journal of clinical pharmacology · 15 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Gobierno
- Dutch Research Council (NWO)
- Subvenciones
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VENI fellowship (grant number 916.10.156))
Según 2 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2017-08-10 · Br J Clin Pharmacol · vol. 83 · número 12 · págs. 2626–2635
- Editorial
- Wiley
- Citado
- 17 citas · más que el 87% de estudios similares · 1.8× el promedio de su campo
- Referencias
- 26 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC-ND
- Áreas de investigación
- Blood Pressure and Hypertension Studies · Muscle metabolism and nutrition · Renin-Angiotensin System Studies
- Palabras clave
- beta-guanidinopropionic acid, creatine, creatine kinase, blood pressure reduction, hypertension, tolerability, safety, plasma concentration, healthy men
- MeSH
- humans, guanidines, creatine, propionates, antihypertensive agents, treatment outcome, administration, oral, drug administration schedule, adolescent, adult, middle aged, netherlands, male, young adult, intention to treat analysis, healthy volunteers
11 autores
- Fares A. Karamat🇳🇱 · autor de correspondenciaAmsterdam UMC Location University of Amsterdam; University of Amsterdam
- Deborah L. Horjus🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Yentl C. Haan🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Lisa van der Woude🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Marianne C. L. Schaap🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Inge Oudman🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Gert A. van Montfrans🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Rienk Nieuwland🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Gajja Sophi Salomons🇳🇱Amsterdam Neuroscience; Amsterdam UMC Location Vrije Universiteit Amsterdam
- Joseph F. Clark🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Lizzy M. Brewster🇺🇸🇳🇱Cincinnati Children's Hospital Medical Center; Amsterdam UMC Location University of Amsterdam; University of Amsterdam
Resumen
El texto original del estudio, en el idioma en que se publicó.
Aims
Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men.
Methods
In this active and placebo-controlled, triple-blind, single-centre trial, we recruited 24 healthy men (18-50 years old, BMI 18.5-29.9 kg m-2 ) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent-to-treat analysis.
Results
Twenty-four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12-Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l-1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53-335.72).
Conclusion
In this first-in-human trial, low-dose GPA was safe and well-tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).
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