<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/NCT04471792</url>
  </required_header>
  <id_info>
    <org_study_id>1150</org_study_id>
    <nct_id>NCT04471792</nct_id>
  </id_info>
  <brief_title>Creatine Use and Muscle Stretching in Peripheral Artery Disease</brief_title>
  <official_title>Creatine Monohydrate Use and Muscle Stretching in Peripheral Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Florida State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Florida State University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To utilize near-infrared spectroscopy to investigate if the research device, which induces&#xD;
      muscle stretching, and creatine loading impact submaximal exercise performance in aged and&#xD;
      PAD patients. Near-infrared spectroscopy (NIRS)-derived tissue oxygenation responses will be&#xD;
      obtained during device placement (muscle stretch) and during a walking test (i.e., six-minute&#xD;
      walk test). Muscle oxygenation at rest and during device placement will be assessed with&#xD;
      Magnetic Resonance Imaging. It is hypothesized that the stretching protocol will improve both&#xD;
      NIRS-derived tissue oxygenation and magnetic resonance-derived muscle oxygenation and that&#xD;
      creatine supplementation will further improve phosphorus metabolite muscle performance. All&#xD;
      patients will undergo either 4 weeks of stretch training with- or- without creatine&#xD;
      supplementation according to previously defined creatine guidelines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lower extremity peripheral artery disease (PAD) has been estimated to impact nearly 8.5&#xD;
      million U.S. adults above the age of 40, significantly increasing the rate of morbidity and&#xD;
      mortality with concomitant decreases in quality of life. These patients are often given&#xD;
      medical therapy (e.g., statins, antiplatelet, anticoagulants) and are also recommended to&#xD;
      begin structured exercise programs. However, the limb ischemia that occurs during physical&#xD;
      activity in these patients often limits exercise tolerance. A previous study by Bauer and&#xD;
      colleagues showed that impaired muscle metabolism is a major contributor to functional&#xD;
      limitations in PAD patients. These data are important in that they show alterations in blood&#xD;
      flow and metabolic machinery likely impact exercise tolerance. As such, the development of&#xD;
      tolerable countermeasures to improve limb blood flow and muscle energetics may increase&#xD;
      adherence to exercise therapy and improve health outcomes in PAD patients. Previous work by&#xD;
      the investigators has shown that daily muscle stretching, achieved via 30-minutes of ankle&#xD;
      dorsiflexion, significantly improved soleus muscle function and muscle blood flow during&#xD;
      exercise in a rat model of aging . In a follow-up study, the investigators have also shown&#xD;
      that this model improves vascular function and walking function in PAD patients. As noted&#xD;
      above, muscle energetics are delayed in PAD patients, so improving the rest-to-exercise&#xD;
      transition with creatine supplementation may help PAD patients sustain exercise longer. The&#xD;
      investigators are now testing to see if an added supplement can further improve the effects&#xD;
      of muscle stretching in PAD patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Actual">December 15, 2022</completion_date>
  <primary_completion_date type="Actual">December 15, 2022</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Randomized, single-blind research design.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Walking tolerance</measure>
    <time_frame>4 weeks</time_frame>
    <description>All patients will perform a pre -and -post 6 minute walking test to assess functional outcomes of muscle stretching and supplementation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Near infrared spectroscopy (NIRS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Use of NIRS on the lateral head of the gastrocnemius muscle in all patients will be performed. NIRS will be measured during a vascular occlusion test, during placement of splint device, and the 6 minute walking test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Use of MRI to assess muscle oxygenation during a vascular occlusion test at rest, and during placement of splint device</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>Creatine monohydrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Creatine Monohydrate will be given at a 5 day loading period (10g/day) followed by a maintenance phase (5 g/day). The objectives of the current trial are to investigate if creatine supplementation plus muscle stretching improves 6-minute walking distance and muscle oxygenation in patients with peripheral artery disease.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cellulose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>These participants will consume a fiber supplement in place of creatine monohydrate at a matched dose with muscle stretching.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Creatine monohydrate</intervention_name>
    <description>Creatine monohydrate will be used in combination with muscle stretching.</description>
    <arm_group_label>Creatine monohydrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Cellulose</intervention_name>
    <description>Cellulose will be used in combination with muscle stretching.</description>
    <arm_group_label>Cellulose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ankle-brachial index (ABI) of 0.90 or less in either leg or clinical diagnosis by a&#xD;
             medical doctor (PAD group only)&#xD;
&#xD;
          2. Stable condition for at least 3 months (PAD group only)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Habitual exercise or cardiovascular rehabilitation program during the past 3 months&#xD;
&#xD;
          2. Critical limb ischemia&#xD;
&#xD;
          3. Blow or above-knee amputation&#xD;
&#xD;
          4. Leg pain at rest&#xD;
&#xD;
          5. Major surgery or lower extremity revascularization in the last 3 months&#xD;
&#xD;
          6. Major medical illness treatment during the prior 12 months&#xD;
&#xD;
          7. Central neurological disease&#xD;
&#xD;
          8. Limited ankle or knee joint range of motion&#xD;
&#xD;
          9. Requirement of oxygen with activity or exercise&#xD;
&#xD;
         10. Heart failure&#xD;
&#xD;
         11. Atrial fibrillation&#xD;
&#xD;
         12. Wheelchair confinement or inability to walk&#xD;
&#xD;
         13. Cognitive disorder&#xD;
&#xD;
         14. Vasculitis problems including Takayasu's arteritis, Berger's disease, collagen disease&#xD;
             or Reynaud's disease&#xD;
&#xD;
         15. Overt cardiovascular disease&#xD;
&#xD;
         16. Metabolic disease&#xD;
&#xD;
         17. Renal disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Judy Muller-Delp, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Florida State University</name>
      <address>
        <city>Tallahassee</city>
        <state>Florida</state>
        <zip>32304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996 Jul;81(1):232-7. doi: 10.1152/jappl.1996.81.1.232.</citation>
    <PMID>8828669</PMID>
  </reference>
  <reference>
    <citation>Hotta K, Behnke BJ, Arjmandi B, Ghosh P, Chen B, Brooks R, Maraj JJ, Elam ML, Maher P, Kurien D, Churchill A, Sepulveda JL, Kabolowsky MB, Christou DD, Muller-Delp JM. Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle. J Physiol. 2018 May 15;596(10):1903-1917. doi: 10.1113/JP275459. Epub 2018 Apr 5.</citation>
    <PMID>29623692</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>February 11, 2023</last_update_submitted>
  <last_update_submitted_qc>February 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Florida State University</investigator_affiliation>
    <investigator_full_name>Judy Delp</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Muscle stretch</keyword>
  <keyword>Creatine Monohydrate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 2, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT04471792/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04471792
org study id: 1150
nct id: NCT04471792
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To utilize near-infrared spectroscopy to investigate if the research device, which induces
      muscle stretching, and creatine loading impact submaximal exercise performance in aged and
      PAD patients. Near-infrared spectroscopy (NIRS)-derived tissue oxygenation responses will be
      obtained during device placement (muscle stretch) and during a walking test (i.e., six-minute
      walk test). Muscle oxygenation at rest and during device placement will be assessed with
      Magnetic Resonance Imaging. It is hypothesized that the stretching protocol will improve both
      NIRS-derived tissue oxygenation and magnetic resonance-derived muscle oxygenation and that
      creatine supplementation will further improve phosphorus metabolite muscle performance. All
      patients will undergo either 4 weeks of stretch training with- or- without creatine
      supplementation according to previously defined creatine guidelines.
Lower extremity peripheral artery disease (PAD) has been estimated to impact nearly 8.5
      million U.S. adults above the age of 40, significantly increasing the rate of morbidity and
      mortality with concomitant decreases in quality of life. These patients are often given
      medical therapy (e.g., statins, antiplatelet, anticoagulants) and are also recommended to
      begin structured exercise programs. However, the limb ischemia that occurs during physical
      activity in these patients often limits exercise tolerance. A previous study by Bauer and
      colleagues showed that impaired muscle metabolism is a major contributor to functional
      limitations in PAD patients. These data are important in that they show alterations in blood
      flow and metabolic machinery likely impact exercise tolerance. As such, the development of
      tolerable countermeasures to improve limb blood flow and muscle energetics may increase
      adherence to exercise therapy and improve health outcomes in PAD patients. Previous work by
      the investigators has shown that daily muscle stretching, achieved via 30-minutes of ankle
      dorsiflexion, significantly improved soleus muscle function and muscle blood flow during
      exercise in a rat model of aging . In a follow-up study, the investigators have also shown
      that this model improves vascular function and walking function in PAD patients. As noted
      above, muscle energetics are delayed in PAD patients, so improving the rest-to-exercise
      transition with creatine supplementation may help PAD patients sustain exercise longer. The
      investigators are now testing to see if an added supplement can further improve the effects
      of muscle stretching in PAD patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: Randomized, single-blind research design.
measure: Walking tolerance
time frame: 4 weeks
description: All patients will perform a pre -and -post 6 minute walking test to assess functional outcomes of muscle stretching and supplementation
measure: Near infrared spectroscopy (NIRS)
time frame: 4 weeks
description: Use of NIRS on the lateral head of the gastrocnemius muscle in all patients will be performed. NIRS will be measured during a vascular occlusion test, during placement of splint device, and the 6 minute walking test.
measure: Magnetic Resonance Imaging (MRI)
time frame: 4 weeks
description: Use of MRI to assess muscle oxygenation during a vascular occlusion test at rest, and during placement of splint device
arm group label: Creatine monohydrate
arm group type: Experimental
description: Creatine Monohydrate will be given at a 5 day loading period (10g/day) followed by a maintenance phase (5 g/day). The objectives of the current trial are to investigate if creatine supplementation plus muscle stretching improves 6-minute walking distance and muscle oxygenation in patients with peripheral artery disease.
arm group label: Cellulose
arm group type: Placebo Comparator
description: These participants will consume a fiber supplement in place of creatine monohydrate at a matched dose with muscle stretching.
intervention type: Drug
intervention name: Creatine monohydrate
description: Creatine monohydrate will be used in combination with muscle stretching.
arm group label: Creatine monohydrate
intervention type: Dietary Supplement
intervention name: Cellulose
description: Cellulose will be used in combination with muscle stretching.
arm group label: Cellulose
criteria: 
gender: All
minimum age: 40 Years
maximum age: 95 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Judy Muller-Delp, Ph.D.
role: Principal Investigator
affiliation: Professor
facility: 
country: United States
citation: Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996 Jul;81(1):232-7. doi: 10.1152/jappl.1996.81.1.232.
PMID: 8828669
citation: Hotta K, Behnke BJ, Arjmandi B, Ghosh P, Chen B, Brooks R, Maraj JJ, Elam ML, Maher P, Kurien D, Churchill A, Sepulveda JL, Kabolowsky MB, Christou DD, Muller-Delp JM. Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle. J Physiol. 2018 May 15;596(10):1903-1917. doi: 10.1113/JP275459. Epub 2018 Apr 5.
PMID: 29623692
responsible party type: Principal Investigator
investigator affiliation: Florida State University
investigator full name: Judy Delp
investigator title: Professor
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
sharing ipd: No
provided document: 