In this study, we will assess the tolerability of GPA in healthy male volunteersFurthermore, we will assess the effect of GPA and creatine on hemodynamic, biochemical parameters and ADP-dependent plateletaggregation of healthy male volunteers.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
het onderzoek is niet van toepassing op een klasse van aandoening(en), maar op fysiologische veranderingen gelijkend op het effect van duurtraining.
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability of GPA
Secondary outcome
The difference in hemodynamic parameters with GPA 100 mg vs placebo and
creatine 5 g, including blood pressure, heart rate, cardiac output, and total
peripheral resistance.
The difference in biochemical parameters with GPA 100 mg vs placebo and
creatine 5 g, including serum GPA, creatine, creatine kinase, glucose,
insuline, and creatinine, and urine GPA, creatine and creatinine.
The difference in ADP-dependent plateletaggregation and thrombocyt count.
Background summary
Beta-guanidinopropionzuur (GPA) is a creatine analogue and competitive
inhibitor of the cellular creatine uptake. The substance is freely available on
the internet and used by sportsmen to increase endurance capacity, promote
weight loss, and improve glucose tolerance.
Animal studies showed that GPA induced an increase in type I oxidative fibers,
with a concomittant increase in oxidative enzyme activity and a decrease in
glycolytic enzyme activity. Endurance training has a similar effect. Our new
data indicate a potential blood pressure lowering effect of GPA in hypertensive
animals.
However, to our knowledge, there are no published data on the effect of GPA on
hemodynamic and biochemical parameters in humans.
Although many studies assessed the effect of creatine on muscle perfomance,
none of those studies reported the effect on hemodynamic parameters. As
described above for the influence of GPA on the energy status, GPA might also
affect local ADP/ATP ratio*s by inhibiting of the reaction: ADP + creatine
phosphate (CrP) * ATP + creatine. In a pilot study we found a dose dependent
reduction of platelet aggregation by creatine kinase at activity levels from
500 to 4000 IU/L, as found in the general population. The effect of GPA on this
mechanism has not yet been studied before.
Study objective
In this study, we will assess the tolerability of GPA in healthy male volunteers
Furthermore, we will assess the effect of GPA and creatine on hemodynamic,
biochemical parameters and ADP-dependent plateletaggregation of healthy male
volunteers.
Study design
100 mg GPA, creatine 5 g, or placebo during one week
Intervention
GPA 100mg versus creatine 5 g and placebo
Study burden and risks
The participants have to be available for 5 days during 1 week. The first visit
(day 0), they will need to fill out a questionnaire, will be physically
examined including blood pressure and EKG, and blood draw. In addition, a
ambulant 24-hour blood pressure measurement will be performed, and the
participant will be asked to collect 24-hour urine. Dependent on the results
the participant will return for the second visit (day 1). During this visit,
after blood pressure measurement, the participant will recieve a capsule with
GPA 100 mg, or creatine 5 g, and placebo. As the doses of GPA and creatine are
not equivalent, we use a "double-dummy" protocol. The participant is asked to
take the following capsules daily in the morning during 7 days:
1 capsule 100 mg GPA or placebo.
10 capsules creatine 500 mg or 10 capsules placebo 500 mg.
Thus, each participant takes 11 capsules daily during 7 days. During the second
visit, a ambulant 24-hour blood pressure measurement will be performed and the
participant will be asked to collect 24-hour urine.
On the third visit (day 3) he will visit the hospital for blood pressure
measurements, blood draw and an ECG. On day 7 and 8, similar investigations
will be performed as on day 1 and 2. Furthermore, the participant is asked to
archivate physical complaints with use of questionnaire. After 3 weeks there
will be a final visit.
GPA is freely available on the internet. The participants will receive low
doses of GPA that we calculated according to the FDA guidelines for estimation
of a safe starting dose in humans. In these guidelines safe doses in animals
are coverted to human equivalent doses. We calculated a safe starting dose of
1200mg. We will use lower doses of 100 and 500mg. Furthermore, there are no FDA
or other reports in formal or informal sources such as google on the side
effects of ingestion of a low dose βGPA in animals or humans. The described
effects were completely reversible. Thus, we don't expect side effects of GPA.
Creatine 5 g is a frequently used dose. No side effects are described with
this dose.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Healthy male volunteers, 18-50 years old, non-obese body mass (BMI 18.5-29.9 kg/m2)
Exclusion criteria
BMI>/= 30 kg/m2, diabetes mellitus, lipid spectrum abnormalities, thyroid, kidney, or liver abnormalities, (history of) cardiovascular disease including TIA and stroke; high blood pressure or the use of antihypertensive drugs at baseline; CK-increasing drugs including statins; use of acetylsalicyl acid or non-steroidal anti-inflammatory drugs (NSAIDs) in the two week prior to the visits; neuromuscular or endocrine disorders; vasculitis; HIV infection; infectious hepatitis; personal or family history of bleeding disorders; sickle cell anaemia or other hereditary anaemia; smoking; vegetarian diet; current urse or use within 2 months prior to start of the trial of beta-guanidinopropionic acid or creatine. The participants are instructed not to perform exercise thee days prior to the basline visit and during the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL38368.018.12 |
| OMON | NL-OMON26749 |