<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02213679</url>
  </required_header>
  <id_info>
    <org_study_id>878/13-EUTC:03</org_study_id>
    <nct_id>NCT02213679</nct_id>
  </id_info>
  <brief_title>Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome</brief_title>
  <official_title>Guanidinoacetic Acid Loading for Chronic Fatigue Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Center for Health, Exercise and Sport Sciences, Serbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Center for Health, Exercise and Sport Sciences, Serbia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology. Recent&#xD;
      studies have shown that CFS is associated with impaired cellular energetics and low levels of&#xD;
      phosphocreatine. Since guanidinoacetic acid (GAA) acts as a highly bioavailable precursor of&#xD;
      creatine it may provide an ideal dietary supplement to facilitate treatment and perhaps&#xD;
      prevention of CFS. The overall hypothesis to be evaluated is that medium-term supplementation&#xD;
      with GAA will improve clinical outcomes in well-defined adult CFS patients via augmented&#xD;
      provision of creatine. Specific aims: (1) To determine the effects of GAA on CFS&#xD;
      symptomatology using a fatigue severity inventory, soreness of locomotive apparatus scales,&#xD;
      and a health-related quality of life survey; (2) To determine the effect of GAA on creatine&#xD;
      metabolism using laboratory studies and magnetic resonance spectroscopy; (3) To characterize&#xD;
      the physiological effects of GAA on work capacity via actigraphy and exercise performance&#xD;
      tests; and (4); To determine the prevalence of subjectively reported side-effects and&#xD;
      biochemical adverse events associated with GAA intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A variety of dietary interventions have been used in the management of CFS, yet no&#xD;
      therapeutic modality demonstrated overall positive results in terms of effectiveness (Whiting&#xD;
      et al. 2001). Previous studies have evaluated the effects of essential fatty acids, vitamins,&#xD;
      minerals and/or enzymes, with findings do not support the use of a broad-spectrum nutritional&#xD;
      supplement in treating CFS-related symptoms (Brouwers et al. 2002). Considering the fact that&#xD;
      patients with CFS have lower levels of high-energy compounds (e.g. phosphocreatine, adenosine&#xD;
      triphosphate) (Block et al. 1998), effective dietary treatment of CFS should be focused on&#xD;
      providing compounds that facilitates cellular bioenergetics. Besides other candidate agents,&#xD;
      guanidinoacetic acid (GAA) could be of particular interest since it occurs naturally in the&#xD;
      human body and acts as an immediate precursor of creatine (Wyss and Kaddurah-Daouk, 2000).&#xD;
      Due to its low cost and high bioavailability (Baker 2009), if proven effective dietary GAA&#xD;
      may be suitable for use in broad CFS population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Multidimensional Fatigue Inventory (MFI) score</measure>
    <time_frame>Baseline and afetr 3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain in the locomotive apparatus</measure>
    <time_frame>Baseline and after 3 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>Baseline and after 3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Daily physical activity</measure>
    <time_frame>Baseline and after 3 months</time_frame>
    <description>Measurement of duration, frequency, and intensity of various types of human physical activity (exercise and nonexercise physical activity)</description>
  </other_outcome>
  <other_outcome>
    <measure>Muscular strength</measure>
    <time_frame>Baseline and after 3 months</time_frame>
    <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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum creatine</measure>
    <time_frame>Baseline and after 3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Side-effects prevalence</measure>
    <time_frame>During 3 months of intervention</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Chronic Fatigue Syndrome</condition>
  <arm_group>
    <arm_group_label>Guanidinoacetic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Supplementation with dietary guanidinoacetic acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Supplementation with cellulose</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Guanidinoacetic acid</intervention_name>
    <description>Dietary supplement</description>
    <arm_group_label>Guanidinoacetic acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults who fulfilled the 1994 CDC criteria for CFS&#xD;
&#xD;
          -  Older than 18 years of age will be candidates for inclusion in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychiatric comorbidity&#xD;
&#xD;
          -  Use of any dietary supplement within 4-weeks prior to the study commencing&#xD;
&#xD;
          -  Pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sergej M Ostojic, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Sport and Physical Education, Novi Sad</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Health, Exercise and Sport Sciences</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <reference>
    <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>
    <PMID>23329885</PMID>
  </reference>
  <reference>
    <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>
    <PMID>23351309</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>24535415</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>January 30, 2017</last_update_submitted>
  <last_update_submitted_qc>January 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Center for Health, Exercise and Sport Sciences, Serbia</investigator_affiliation>
    <investigator_full_name>Assoc. Prof. Sergej M. Ostojic, MD, PhD</investigator_full_name>
    <investigator_title>Associate Professor of Biomedical Sciences</investigator_title>
  </responsible_party>
  <keyword>Creatine</keyword>
  <keyword>Guanidinoacetic acid</keyword>
  <keyword>Intervention</keyword>
  <keyword>Fatigue</keyword>
  <keyword>Muscle strength</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatigue Syndrome, Chronic</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02213679
org study id: 878/13-EUTC:03
nct id: NCT02213679
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in the Multidimensional Fatigue Inventory (MFI) score
time frame: Baseline and afetr 3 months
measure: Pain in the locomotive apparatus
time frame: Baseline and after 3 months
measure: Health-related quality of life
time frame: Baseline and after 3 months
measure: Daily physical activity
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: Muscular strength
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: Serum creatine
time frame: Baseline and after 3 months
measure: Side-effects prevalence
time frame: During 3 months of intervention
arm group label: Guanidinoacetic acid
arm group type: Experimental
description: Supplementation with dietary guanidinoacetic acid
arm group label: Placebo
arm group type: Placebo Comparator
description: Supplementation with cellulose
intervention type: Dietary Supplement
intervention name: Guanidinoacetic acid
description: Dietary supplement
arm group label: Guanidinoacetic acid
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sergej M Ostojic, MD, PhD
role: Principal Investigator
affiliation: Faculty of Sport and Physical Education, Novi Sad
facility: 
country: Serbia
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
responsible party type: Principal Investigator
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
mesh term: Fatigue Syndrome, Chronic
mesh term: Syndrome
mesh term: Fatigue
sharing ipd: Undecided