## Protocol Section
### Identification Module
**NCT ID:** NCT02213679

**Brief Title:** Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome

**Official Title:** Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome

#### Organization Study ID Info
**ID:** 878/13-EUTC:03
#### Organization
**Class:** OTHER
**Full Name:** Center for Health, Exercise and Sport Sciences, Serbia
### Status Module
#### Completion Date
**Date:** 2015-07

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2017-02-01

**Type:** ESTIMATED

**Last Update Submit Date:** 2017-01-30

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2015-06

**Type:** ACTUAL

#### Start Date
**Date:** 2014-08

**Status Verified Date:** 2017-01

#### Study First Post Date
**Date:** 2014-08-11
**Type:** ESTIMATED
**Study First Submit Date:** 2014-08-05
**Study First Submit QC Date:** 2014-08-07
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Center for Health, Exercise and Sport Sciences, Serbia

#### Responsible Party

**Investigator Affiliation:** Center for Health, Exercise and Sport Sciences, Serbia

**Investigator Full Name:** Assoc. Prof. Sergej M. Ostojic, MD, PhD

**Investigator Title:** Associate Professor of Biomedical Sciences

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Chronic Fatigue Syndrome

**Keywords:**

- Creatine

- Guanidinoacetic acid

- Intervention

- Fatigue

- Muscle strength

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** SUPPORTIVE_CARE

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Supplementation with dietary guanidinoacetic acid

**Intervention Names:**

- Dietary Supplement: Guanidinoacetic acid

**Label:** Guanidinoacetic acid

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Supplementation with cellulose

**Intervention Names:**

- Other: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Guanidinoacetic acid

**Description:** Dietary supplement

**Name:** Guanidinoacetic acid

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Placebo

**Name:** Placebo

**Type:** OTHER

### Outcomes Module

#### Other Outcomes

**Measure:** Health-related quality of life

**Time Frame:** Baseline and after 3 months

**Description:** Measurement of duration, frequency, and intensity of various types of human physical activity (exercise and nonexercise physical activity)

**Measure:** Daily physical activity

**Time Frame:** Baseline and after 3 months

**Description:** For muscular performance, maximal voluntary strength of knee extensor muscles will be measured bilaterally using an isometric dynamometer during static knee joint movement with leg at 165º of flexion (180º = leg fully extended). The better of two efforts for each leg will be recorded with cumulative value presented as total isometric strength.

**Measure:** Muscular strength

**Time Frame:** Baseline and after 3 months

**Measure:** Serum creatine

**Time Frame:** Baseline and after 3 months

**Measure:** Side-effects prevalence

**Time Frame:** During 3 months of intervention

#### Primary Outcomes

**Measure:** Change in the Multidimensional Fatigue Inventory (MFI) score

**Time Frame:** Baseline and afetr 3 months

#### Secondary Outcomes

**Measure:** Pain in the locomotive apparatus

**Time Frame:** Baseline and after 3 months

### Eligibility Module

**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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Belgrade

**Country:** Serbia

**Facility:** Center for Health, Exercise and Sport Sciences

**Zip:** 11000

#### Overall Officials

**Official 1:**

**Affiliation:** Faculty of Sport and Physical Education, Novi Sad

**Name:** Sergej M Ostojic, MD, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### 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.

**PMID:** 23329885

**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.

**PMID:** 23351309

**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.

**PMID:** 24535415

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000004679

- Term: Encephalomyelitis

- ID: D000090862

- Term: Neuroinflammatory Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC01

- Name: Infections

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M8364

- Name: Fatigue

- Relevance: HIGH

- As Found: Fatigue

- ID: M18260

- Name: Fatigue Syndrome, Chronic

- Relevance: HIGH

- As Found: Chronic Fatigue Syndrome

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7842

- Name: Encephalomyelitis

- Relevance: LOW

- As Found: Unknown

- ID: M2803

- Name: Neuroinflammatory Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000015673

- Term: Fatigue Syndrome, Chronic

- ID: D000013577

- Term: Syndrome

- ID: D000005221

- Term: Fatigue

### Intervention Browse Module - Browse Branches

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T385

- Name: Creatine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
