<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/NCT01694602</url>
  </required_header>
  <id_info>
    <org_study_id>12-064</org_study_id>
    <secondary_id>2R44AR054993-02</secondary_id>
    <nct_id>NCT01694602</nct_id>
  </id_info>
  <brief_title>Non-Invasive Assessment of Skeletal Muscle Loss in Cancer Patients - Phase II</brief_title>
  <acronym>3MH-2</acronym>
  <official_title>Non-Invasive Assessment of Skeletal Muscle Loss in Cancer Patients - Phase 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Medical Branch, Galveston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Medical Branch, Galveston</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of this research is to develop a non-invasive approach to evaluate the&#xD;
      production of 3-methylhistidine (3MH)in cancer patients, as a potential means of determining&#xD;
      which patients are at high risk for future development of cancer induced skeletal muscle&#xD;
      atrophy.&#xD;
&#xD;
      Rationale: The approach is based on the hypothesis that after an oral dose of deuterated&#xD;
      3-methylhistidine (D-3MH), the slope of the terminal portion of the decay curve (&gt; 12 hours&#xD;
      post-dosing) for the tracer/tracee (D-3MH/3MH) in the free 3MH pool is proportional to the&#xD;
      rate constant for myofibrillar protein degradation and can be determined from spot urine&#xD;
      samples.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The long-term objective of this research is to develop a non-invasive approach for assessment&#xD;
      of de novo 3MH production in cancer patients early in the course of the disease as a way of&#xD;
      assessing which patients are at high risk for future development of skeletal muscle atrophy.&#xD;
      The approach is based on: 1) the known increase in de novo production of 3-methylhistidine&#xD;
      (3MH) from muscle protein breakdown in said patients as a consequence of their unique&#xD;
      disease-host interactions, and 2) earlier demonstration that de novo 3MH production can be&#xD;
      measured in vivo using isotope dilution.&#xD;
&#xD;
      During this Phase-II project, we propose to conduct a statistically powerful prospective&#xD;
      investigation to demonstrate that measurement of the slope of the terminal decay curve (rate&#xD;
      constant) with our approach in newly diagnosed cancer patients predicts future development of&#xD;
      muscle wasting. We expect the outcome of the combined Phase-I and Phase-II research to lead&#xD;
      to the early identification of elevated muscle catabolism in at-risk patients so that medical&#xD;
      intervention can prevent future muscle atrophy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of myofibrillar protein degradation rate constant and slope of terminal decay curve.</measure>
    <time_frame>Spot urine (multiple) collections between 12 to 17 hours of D-3MH ingestion.</time_frame>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">8</enrollment>
  <condition>Cachexia</condition>
  <arm_group>
    <arm_group_label>Newly Diagnosed NSCLC patients</arm_group_label>
    <description>In this study, newly diagnosed NSCLC patients who are not candidates for curative resection, will receive a (non-radioactive) oral dose of deuterated 3-methylhistidine (D-3MH).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>(non-radioactive) Oral deuterated 3-methylhistidine (D-3MH)</intervention_name>
    <description>Oral dose of 9.0 mg (50 μmol) TAU-METHYL-L-HISTIDINE (METHYL-D3), Cambridge Isotope Laboratory, Cambridge, Massachusetts.</description>
    <arm_group_label>Newly Diagnosed NSCLC patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Spot urine samples.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        We will conduct a longitudinal study (repeated measures design) in 30 newly diagnosed&#xD;
        nonsmall cell lung cancer (NSCLC) patients who are not candidates for curative resection.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  (1) histological or cytological evidence of NSCLC without curative options;&#xD;
&#xD;
          -  (2) over 18 years of age;&#xD;
&#xD;
          -  (3) patient reported weight loss of ≤5% of usual body weight in the last 6 months;&#xD;
&#xD;
          -  (4) life expectancy of greater than 6 months based on the judgement of treating&#xD;
             physician;&#xD;
&#xD;
          -  (5) serum creatinine ≤1.5 times the upper limit of normal; and&#xD;
&#xD;
          -  (6) willing and able to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) malabsorption, intractable vomiting or gastrointestinal obstruction&#xD;
&#xD;
          -  2) congestive heart failure&#xD;
&#xD;
          -  3) edema or ascites&#xD;
&#xD;
          -  4) liver function test results that will preclude administration of prescribed therapy&#xD;
&#xD;
          -  5) pregnant, nursing, or, if of child-bearing age, unwilling to use contraceptives&#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>William J Durham, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Medical Branch (UTMB Health), Galveston, Texas.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555-0361</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>July 1, 2015</last_update_submitted>
  <last_update_submitted_qc>July 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 2, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cachexia</keyword>
  <keyword>Sarcopenia</keyword>
  <keyword>De Novo</keyword>
  <keyword>Deuterated</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wasting Syndrome</mesh_term>
    <mesh_term>Cachexia</mesh_term>
  </condition_browse>
  <!-- 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/NCT01694602
org study id: 12-064
secondary id: 2R44AR054993-02
nct id: NCT01694602
lead sponsor: 
has dmc: No
The overall aim of this research is to develop a non-invasive approach to evaluate the
      production of 3-methylhistidine (3MH)in cancer patients, as a potential means of determining
      which patients are at high risk for future development of cancer induced skeletal muscle
      atrophy.

      Rationale: The approach is based on the hypothesis that after an oral dose of deuterated
      3-methylhistidine (D-3MH), the slope of the terminal portion of the decay curve (> 12 hours
      post-dosing) for the tracer/tracee (D-3MH/3MH) in the free 3MH pool is proportional to the
      rate constant for myofibrillar protein degradation and can be determined from spot urine
      samples.
The long-term objective of this research is to develop a non-invasive approach for assessment
      of de novo 3MH production in cancer patients early in the course of the disease as a way of
      assessing which patients are at high risk for future development of skeletal muscle atrophy.
      The approach is based on: 1) the known increase in de novo production of 3-methylhistidine
      (3MH) from muscle protein breakdown in said patients as a consequence of their unique
      disease-host interactions, and 2) earlier demonstration that de novo 3MH production can be
      measured in vivo using isotope dilution.

      During this Phase-II project, we propose to conduct a statistically powerful prospective
      investigation to demonstrate that measurement of the slope of the terminal decay curve (rate
      constant) with our approach in newly diagnosed cancer patients predicts future development of
      muscle wasting. We expect the outcome of the combined Phase-I and Phase-II research to lead
      to the early identification of elevated muscle catabolism in at-risk patients so that medical
      intervention can prevent future muscle atrophy.
observational model: Case-Only
time perspective: Prospective
measure: Determination of myofibrillar protein degradation rate constant and slope of terminal decay curve.
time frame: Spot urine (multiple) collections between 12 to 17 hours of D-3MH ingestion.
arm group label: Newly Diagnosed NSCLC patients
description: In this study, newly diagnosed NSCLC patients who are not candidates for curative resection, will receive a (non-radioactive) oral dose of deuterated 3-methylhistidine (D-3MH).
intervention type: Biological
intervention name: (non-radioactive) Oral deuterated 3-methylhistidine (D-3MH)
description: Oral dose of 9.0 mg (50 μmol) TAU-METHYL-L-HISTIDINE (METHYL-D3), Cambridge Isotope Laboratory, Cambridge, Massachusetts.
arm group label: Newly Diagnosed NSCLC patients
Spot urine samples.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: William J Durham, PhD
role: Principal Investigator
affiliation: The University of Texas Medical Branch (UTMB Health), Galveston, Texas.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Wasting Syndrome
mesh term: Cachexia