Clinical trial NCT02213679: Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome
Official title: Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Fatigue Syndrome
Keywords: Creatine
Guanidinoacetic acid
Intervention
Fatigue
Muscle strength
Lead sponsor: Center for Health Sciences, Serbia
Sponsor class: OTHER
First posted: 2014-08-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology. Recent studies have shown that CFS is associated with impaired cellular energetics and low levels of phosphocreatine. Since guanidinoacetic acid (GAA) acts as a highly bioavailable precursor of creatine it may provide an ideal dietary supplement to facilitate treatment and perhaps prevention of CFS. The overall hypothesis to be evaluated is that medium-term supplementation with GAA will improve clinical outcomes in well-defined adult CFS patients via augmented provision of creatine. Specific aims: (1) To determine the effects of GAA on CFS symptomatology using a fatigue severity inventory, soreness of locomotive apparatus scales, and a health-related quality of life survey; (2) To determine the effect of GAA on creatine metabolism using laboratory studies and magnetic resonance spectroscopy; (3) To characterize the physiological effects of GAA on work capacity via actigraphy and exercise performance tests; and (4); To determine the prevalence of subjectively reported side-effects and biochemical adverse events associated with GAA intervention.

Detailed description: A variety of dietary interventions have been used in the management of CFS, yet no therapeutic modality demonstrated overall positive results in terms of effectiveness (Whiting et al. 2001). Previous studies have evaluated the effects of essential fatty acids, vitamins, minerals and/or enzymes, with findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms (Brouwers et al. 2002). Considering the fact that patients with CFS have lower levels of high-energy compounds (e.g. phosphocreatine, adenosine triphosphate) (Block et al. 1998), effective dietary treatment of CFS should be focused on providing compounds that facilitates cellular bioenergetics. Besides other candidate agents, guanidinoacetic acid (GAA) could be of particular interest since it occurs naturally in the human body and acts as an immediate precursor of creatine (Wyss and Kaddurah-Daouk, 2000). Due to its low cost and high bioavailability (Baker 2009), if proven effective dietary GAA may be suitable for use in broad CFS population.

Eligibility criteria: Inclusion Criteria:

* Adults who fulfilled the 1994 CDC criteria for CFS
* Older than 18 years of age will be candidates for inclusion in the study.

Exclusion Criteria:

* Psychiatric comorbidity
* Use of any dietary supplement within 4-weeks prior to the study commencing
* Pregnant

Primary outcomes:
measure: Change in the Multidimensional Fatigue Inventory (MFI) score
timeFrame: Baseline and afetr 3 months
Secondary outcomes:
measure: Pain in the locomotive apparatus
timeFrame: Baseline and after 3 months
Other outcomes:
measure: Health-related quality of life
timeFrame: Baseline and after 3 months
measure: Daily physical activity
timeFrame: Baseline and after 3 months
measure: Muscular strength
timeFrame: Baseline and after 3 months
measure: Serum creatine
timeFrame: Baseline and after 3 months
measure: Side-effects prevalence
timeFrame: During 3 months of intervention
Locations:
city: Belgrade
country: Serbia
facility: Center for Health, Exercise and Sport Sciences
Study officials:
affiliation: Faculty of Sport and Physical Education, Novi Sad
name: Sergej M Ostojic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ostojic SM, Niess B, Stojanovic M, Obrenovic M. Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans. Int J Med Sci. 2013;10(2):141-7. doi: 10.7150/ijms.5125. Epub 2013 Jan 3.
citation: Ostojic SM, Niess B, Stojanovic M, Obrenovic M. Co-administration of methyl donors along with guanidinoacetic acid reduces the incidence of hyperhomocysteinaemia compared with guanidinoacetic acid administration alone. Br J Nutr. 2013 Sep 14;110(5):865-70. doi: 10.1017/S0007114512005879. Epub 2013 Jan 28.
citation: Ostojic SM, Stojanovic M, Drid P, Hoffman JR. Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels. Eur J Nutr. 2014 Dec;53(8):1637-43. doi: 10.1007/s00394-014-0669-0. Epub 2014 Feb 18.