<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/NCT03292315</url>
  </required_header>
  <id_info>
    <org_study_id>BAU-17-038</org_study_id>
    <nct_id>NCT03292315</nct_id>
  </id_info>
  <brief_title>Once Weekly GLP-1 in Persons With Spinal Cord Injury</brief_title>
  <official_title>The Efficacy of a Once Weekly Glucagon-Like Peptide-1 Agonist on Body Weight/Composition and Metabolic Parameters in Persons With SCI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James J. Peters Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kessler Institute for Rehabilitation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>James J. Peters Veterans Affairs Medical Center</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>
      Chronic spinal cord injury (SCI) results in adverse soft tissue body composition changes and&#xD;
      an extremely sedentary lifestyle. These abrupt changes often lead to a high prevalence of&#xD;
      cardiometabolic diseases, such as impaired glucose tolerance/diabetes mellitus and&#xD;
      dyslipidemia, conditions which predispose those with SCI to an increased risk for&#xD;
      cardiovascular disease compared to the general population. Due to paralysis and wheel chair&#xD;
      dependence, maintaining an adequate level of physical activity to counteract these&#xD;
      deleterious metabolic changes presents a unique obstacle because conventional first line&#xD;
      interventions are lifestyle modifications (e.g., diet and exercise), which may be difficult&#xD;
      to achieve. Recently, a new medication has been approved by the Food and Drug Administration&#xD;
      to improve glycemic control in individuals with diabetes mellitus, and it has also been&#xD;
      investigated as an off-label treatment to induce weight loss. Glucagon-like peptide-1 (GLP-1)&#xD;
      agonists are a class of drugs designed to mimic the endogenous incretin hormones released&#xD;
      from the gut in a glucose dependent manner following a meal. The mechanisms of action for&#xD;
      this drug class of medications include stimulation of glucose-dependent insulin secretion,&#xD;
      inhibiting glucagon release, slowed gastric emptying, and reduction of postprandial glucose&#xD;
      excursions following food intake. In addition to improved glycemic control, this class of&#xD;
      medications also shows promise for its non-glycemic action of facilitating weight loss. The&#xD;
      method of delivery of the GLP-1's is by self-administered injections once daily or once&#xD;
      weekly, depending on the severity of the clinical case and therapeutic targets for a specific&#xD;
      patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obesity is an underlying condition that predisposes to the development of several medical&#xD;
      disorders and diseases. It is well appreciated that obesity has reached pandemic proportions&#xD;
      in Western societies. The World Health Organization (WHO) estimates that 1.9 billion adults&#xD;
      worldwide are overweight and 600 million of these individuals are further sub-classified as&#xD;
      obese, with a 44% estimated burden for type 2 diabetes mellitus (T2DM) being attributed to&#xD;
      being overweight/obese, as well as a 23% estimated burden for heart disease (&quot;Obesity and&#xD;
      overweight,&quot; 2016). Excess adipose tissue is assumed to play an integral role in the&#xD;
      pathogenesis of vascular dysfunction and the development of T2DM (Lau, Dhillon, Yan, Szmitko,&#xD;
      &amp; Verma, 2005).&#xD;
&#xD;
      During the acute and chronic phases of SCI, marked adverse changes occur in soft tissue body&#xD;
      composition and associated carbohydrate and lipid metabolism. After an initial rapid loss of&#xD;
      lean tissue below the neurological level of injury, a more insidious and progressive lean&#xD;
      tissue loss is observed (Modlesky et al., 2004; Spungen et al., 2003), which is accompanied&#xD;
      by an increased total body adiposity (Spungen et al., 2003), with accumulation of fat in the&#xD;
      abdominal (e.g., visceral) compartment (Gorgey, Mather, Poarch, &amp; Gater, 2011). These adverse&#xD;
      changes to body composition contribute to, and are associated with, a higher prevalence of&#xD;
      insulin resistance and disorders of carbohydrate metabolism (e.g., impaired glucose tolerance&#xD;
      and T2DM) than that reported in the general population (Bauman &amp; Spungen, 1994). The primary&#xD;
      approach to treat T2DM in the general population is diet and exercise (i.e., lifestyle&#xD;
      modification). Of note, the profound inactivity and adverse soft tissue body composition&#xD;
      changes that occur in individuals after SCI result in metabolic morbidity which is extremely&#xD;
      difficult to manage with lifestyle modification alone. Conventional therapeutic strategies&#xD;
      employed in the adjunctive treatment of carbohydrate metabolism disorders in the general&#xD;
      population include several pharmacological approaches to maintain and improve glycemic&#xD;
      control are in standard practice and include reducing the serum glucose concentration (i.e.,&#xD;
      insulin, sulphonylureas, thiazolidinediones or glitazones), suppressing hepatic&#xD;
      gluconeogenesis (i.e., insulin, biguanides), stimulating endogenous insulin secretion (i.e.,&#xD;
      sulphonylureas), and/or by inhibiting glucose renal reabsorption and increasing glycosuria&#xD;
      (i.e., SGLT-2 inhibitors).&#xD;
&#xD;
      In 2005 a new class of drugs was approved for the treatment for T2DM by targeting the GLP-1&#xD;
      receptor. Exenatide is a GLP-1 agonist that acts as an incretin hormone, and it belongs to a&#xD;
      class of gastrointestinal hormones which are released from the L cells of the intestines in&#xD;
      response to food ingestion that, as one of its mechanisms of action, increase insulin&#xD;
      secretion from pancreatic beta cells (Vilsboll et al., 2003). This phenomenon that was coined&#xD;
      &quot;the incretin effect&quot; in the 1960's described the significantly higher plasma insulin levels&#xD;
      following orally versus intravenously administered glucose, which can account for 50 to 70%&#xD;
      of the insulin secretion observed after food intake (Baggio &amp; Drucker, 2007). Treatment with&#xD;
      GLP-1's has increased over the past several years because of their mechanism of action to&#xD;
      increase insulin secretion, inhibit glucagon release in a glucose-dependent manner, thus&#xD;
      minimizing the risk for hypoglycemia (Baggio &amp; Drucker, 2007; Nauck, Stockmann, Ebert, &amp;&#xD;
      Creutzfeldt, 1986; Vilsboll, Krarup, Madsbad, &amp; Holst, 2002). Numerous multi-ethnic and&#xD;
      multi-national trials have been performed with exenatide, but none have been reported in&#xD;
      persons with SCI. Previous investigation with exenatide once-weekly in able-bodied&#xD;
      individuals has resulted in weight loss ranging from 1.6 to 3.9 kg following 24 weeks of&#xD;
      intervention (Bergenstal et al., 2010; Blevins et al., 2011; Buse et al., 2013; Chiquette,&#xD;
      Toth, Ramirez, Cobble, &amp; Chilton, 2012; Davies et al., 2013; Diamant et al., 2010; Drucker et&#xD;
      al., 2008; Inagaki, Atsumi, Oura, Saito, &amp; Imaoka, 2012; Ji et al., 2013; Russell-Jones et&#xD;
      al., 2012). As such, to date there is no evidence of the potential efficacy of exenatide to&#xD;
      result in weight loss, improve glycemic control, and/or reduce insulin resistance in persons&#xD;
      with SCI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Actual">March 1, 2023</completion_date>
  <primary_completion_date type="Actual">March 1, 2020</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Body Weight</measure>
    <time_frame>Baseline, Week 13, Week 26</time_frame>
    <description>Efficacy of GLP-1 to reduce total body weight determined by Dual Energy Absorptiometry (DXA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)</measure>
    <time_frame>Baseline, Week 13, Week 26</time_frame>
    <description>Efficacy of GLP-1 to reduce HOMA-IR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Homeostatic Model Assessment of Beta-Cell Function (HOMA-B)</measure>
    <time_frame>Baseline, Week 13, Week 26</time_frame>
    <description>Efficacy of GLP-1 to increase HOMA-B</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body Fat</measure>
    <time_frame>Baseline, Week 13, Week 26</time_frame>
    <description>Efficacy of GLP-1 to reduce total body fat determined by Dual Energy Absorptiometry (DXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycated Hemoglobin (HbA1C)</measure>
    <time_frame>Baseline, Week 13, Week 26</time_frame>
    <description>Efficacy of GLP-1 to reduce HbA1C</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <condition>Insulin Resistance</condition>
  <condition>Pre Diabetes</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Semaglutide 1MG Injection [Ozempic]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 subjects will be randomized to receive once weekly injection of Semaglutide (Ozempic1mg) for 26 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Intervention</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>10 subjects will be randomized to receive no intervention for 26 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semaglutide 1MG Injection [Ozempic]</intervention_name>
    <description>Once weekly injection of 1mg of Semaglutide.</description>
    <arm_group_label>Semaglutide 1MG Injection [Ozempic]</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No Intervention</intervention_name>
    <description>No injection will be administered</description>
    <arm_group_label>No Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, age 18 to 69;&#xD;
&#xD;
          2. Chronic (e.g., duration of injury greater than 3 years) stable SCI (regardless of&#xD;
             level of neurological injury);&#xD;
&#xD;
          3. ASIA A-D (non-ambulatory defined as not able to weight bear for more than 20% of the&#xD;
             day);&#xD;
&#xD;
          4. Obese Percent Body Fat defined as &gt; 25% for men and &gt; 35% for women (as determined by&#xD;
             screening DXA scan);&#xD;
&#xD;
          5. Insulin Resistant as determined at screening: (FPI, ≥15 µU/ml); -OR-&#xD;
&#xD;
          6. Pre-diabetic, as determined by any one of the following:&#xD;
&#xD;
               1. HbA1C ≥ 5.7% and &lt; 6.4%; or&#xD;
&#xD;
               2. Impaired glucose tolerance by FSG ≥100 mg/dl and &lt; 125 mg/dl and/or the 2 hour&#xD;
                  serum glucose concentration (after an OGTT) ≥ 140 mg/dl and &lt; 200 mg/dl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Personal history of or family history of medullary thyroid carcinoma;&#xD;
&#xD;
          2. History of multiple endocrine neoplasia syndrome type 2;&#xD;
&#xD;
          3. History of pancreatitis;&#xD;
&#xD;
          4. Existing diagnosis of diabetes mellitus, or the results from screening OGTT that&#xD;
             identify diabetes mellitus (previously undiagnosed); laboratory thresholds for&#xD;
             exclusion will be as follows: HbA1C ≥6.5%, fasting plasma glucose &gt;126 mg/dl, or 2&#xD;
             hour value &gt;200 mg/dl;&#xD;
&#xD;
          5. Receiving treatment for impaired glucose metabolism (i.e., insulin, secretagogues, or&#xD;
             other agents to modify peripheral insulin sensitivity or serum glucose concentration);&#xD;
&#xD;
          6. Reduced kidney function (by glomerular filtration rate (GFR &lt;60 ml/min) or liver&#xD;
             function tests (any single LFT ≥ 2.5 times above the upper limit of normal) as&#xD;
             determined by test results at screening and any time point of the study;&#xD;
&#xD;
          7. Elevated calcitonin level (as determined at screening to rule out thyroid cancer);&#xD;
&#xD;
          8. Pregnancy or women who may become pregnant during the course of the study, or those&#xD;
             who are nursing;&#xD;
&#xD;
          9. Medically unstable;&#xD;
&#xD;
         10. Acute illness or infection;&#xD;
&#xD;
         11. Diminished mental capacity; and&#xD;
&#xD;
         12. Inability or unwillingness of subject to provide informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Kessler Institute for Rehabilitation</name>
      <address>
        <city>West Orange</city>
        <state>New Jersey</state>
        <zip>07052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>March 10, 2023</last_update_submitted>
  <last_update_submitted_qc>March 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>James J. Peters Veterans Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>William A. Bauman, M.D.</investigator_full_name>
    <investigator_title>Director, Clinical Investigator, National Center for the Medical Consequences of Spinal Cord Injury</investigator_title>
  </responsible_party>
  <keyword>Glucagon-Like Peptide-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Prediabetic State</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03292315
org study id: BAU-17-038
nct id: NCT03292315
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Chronic spinal cord injury (SCI) results in adverse soft tissue body composition changes and
      an extremely sedentary lifestyle. These abrupt changes often lead to a high prevalence of
      cardiometabolic diseases, such as impaired glucose tolerance/diabetes mellitus and
      dyslipidemia, conditions which predispose those with SCI to an increased risk for
      cardiovascular disease compared to the general population. Due to paralysis and wheel chair
      dependence, maintaining an adequate level of physical activity to counteract these
      deleterious metabolic changes presents a unique obstacle because conventional first line
      interventions are lifestyle modifications (e.g., diet and exercise), which may be difficult
      to achieve. Recently, a new medication has been approved by the Food and Drug Administration
      to improve glycemic control in individuals with diabetes mellitus, and it has also been
      investigated as an off-label treatment to induce weight loss. Glucagon-like peptide-1 (GLP-1)
      agonists are a class of drugs designed to mimic the endogenous incretin hormones released
      from the gut in a glucose dependent manner following a meal. The mechanisms of action for
      this drug class of medications include stimulation of glucose-dependent insulin secretion,
      inhibiting glucagon release, slowed gastric emptying, and reduction of postprandial glucose
      excursions following food intake. In addition to improved glycemic control, this class of
      medications also shows promise for its non-glycemic action of facilitating weight loss. The
      method of delivery of the GLP-1's is by self-administered injections once daily or once
      weekly, depending on the severity of the clinical case and therapeutic targets for a specific
      patient.
Obesity is an underlying condition that predisposes to the development of several medical
      disorders and diseases. It is well appreciated that obesity has reached pandemic proportions
      in Western societies. The World Health Organization (WHO) estimates that 1.9 billion adults
      worldwide are overweight and 600 million of these individuals are further sub-classified as
      obese, with a 44% estimated burden for type 2 diabetes mellitus (T2DM) being attributed to
      being overweight/obese, as well as a 23% estimated burden for heart disease ("Obesity and
      overweight," 2016). Excess adipose tissue is assumed to play an integral role in the
      pathogenesis of vascular dysfunction and the development of T2DM (Lau, Dhillon, Yan, Szmitko,
      & Verma, 2005).

      During the acute and chronic phases of SCI, marked adverse changes occur in soft tissue body
      composition and associated carbohydrate and lipid metabolism. After an initial rapid loss of
      lean tissue below the neurological level of injury, a more insidious and progressive lean
      tissue loss is observed (Modlesky et al., 2004; Spungen et al., 2003), which is accompanied
      by an increased total body adiposity (Spungen et al., 2003), with accumulation of fat in the
      abdominal (e.g., visceral) compartment (Gorgey, Mather, Poarch, & Gater, 2011). These adverse
      changes to body composition contribute to, and are associated with, a higher prevalence of
      insulin resistance and disorders of carbohydrate metabolism (e.g., impaired glucose tolerance
      and T2DM) than that reported in the general population (Bauman & Spungen, 1994). The primary
      approach to treat T2DM in the general population is diet and exercise (i.e., lifestyle
      modification). Of note, the profound inactivity and adverse soft tissue body composition
      changes that occur in individuals after SCI result in metabolic morbidity which is extremely
      difficult to manage with lifestyle modification alone. Conventional therapeutic strategies
      employed in the adjunctive treatment of carbohydrate metabolism disorders in the general
      population include several pharmacological approaches to maintain and improve glycemic
      control are in standard practice and include reducing the serum glucose concentration (i.e.,
      insulin, sulphonylureas, thiazolidinediones or glitazones), suppressing hepatic
      gluconeogenesis (i.e., insulin, biguanides), stimulating endogenous insulin secretion (i.e.,
      sulphonylureas), and/or by inhibiting glucose renal reabsorption and increasing glycosuria
      (i.e., SGLT-2 inhibitors).

      In 2005 a new class of drugs was approved for the treatment for T2DM by targeting the GLP-1
      receptor. Exenatide is a GLP-1 agonist that acts as an incretin hormone, and it belongs to a
      class of gastrointestinal hormones which are released from the L cells of the intestines in
      response to food ingestion that, as one of its mechanisms of action, increase insulin
      secretion from pancreatic beta cells (Vilsboll et al., 2003). This phenomenon that was coined
      "the incretin effect" in the 1960's described the significantly higher plasma insulin levels
      following orally versus intravenously administered glucose, which can account for 50 to 70%
      of the insulin secretion observed after food intake (Baggio & Drucker, 2007). Treatment with
      GLP-1's has increased over the past several years because of their mechanism of action to
      increase insulin secretion, inhibit glucagon release in a glucose-dependent manner, thus
      minimizing the risk for hypoglycemia (Baggio & Drucker, 2007; Nauck, Stockmann, Ebert, &
      Creutzfeldt, 1986; Vilsboll, Krarup, Madsbad, & Holst, 2002). Numerous multi-ethnic and
      multi-national trials have been performed with exenatide, but none have been reported in
      persons with SCI. Previous investigation with exenatide once-weekly in able-bodied
      individuals has resulted in weight loss ranging from 1.6 to 3.9 kg following 24 weeks of
      intervention (Bergenstal et al., 2010; Blevins et al., 2011; Buse et al., 2013; Chiquette,
      Toth, Ramirez, Cobble, & Chilton, 2012; Davies et al., 2013; Diamant et al., 2010; Drucker et
      al., 2008; Inagaki, Atsumi, Oura, Saito, & Imaoka, 2012; Ji et al., 2013; Russell-Jones et
      al., 2012). As such, to date there is no evidence of the potential efficacy of exenatide to
      result in weight loss, improve glycemic control, and/or reduce insulin resistance in persons
      with SCI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Body Weight
time frame: Baseline, Week 13, Week 26
description: Efficacy of GLP-1 to reduce total body weight determined by Dual Energy Absorptiometry (DXA)
measure: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
time frame: Baseline, Week 13, Week 26
description: Efficacy of GLP-1 to reduce HOMA-IR
measure: Homeostatic Model Assessment of Beta-Cell Function (HOMA-B)
time frame: Baseline, Week 13, Week 26
description: Efficacy of GLP-1 to increase HOMA-B
measure: Body Fat
time frame: Baseline, Week 13, Week 26
description: Efficacy of GLP-1 to reduce total body fat determined by Dual Energy Absorptiometry (DXA)
measure: Glycated Hemoglobin (HbA1C)
time frame: Baseline, Week 13, Week 26
description: Efficacy of GLP-1 to reduce HbA1C
arm group label: Semaglutide 1MG Injection [Ozempic]
arm group type: Experimental
description: 20 subjects will be randomized to receive once weekly injection of Semaglutide (Ozempic1mg) for 26 weeks.
arm group label: No Intervention
arm group type: Other
description: 10 subjects will be randomized to receive no intervention for 26 weeks.
intervention type: Drug
intervention name: Semaglutide 1MG Injection [Ozempic]
description: Once weekly injection of 1mg of Semaglutide.
arm group label: Semaglutide 1MG Injection [Ozempic]
intervention type: Other
intervention name: No Intervention
description: No injection will be administered
arm group label: No Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: James J. Peters Veterans Affairs Medical Center
investigator full name: William A. Bauman, M.D.
investigator title: Director, Clinical Investigator, National Center for the Medical Consequences of Spinal Cord Injury
mesh term: Spinal Cord Injuries
mesh term: Insulin Resistance
mesh term: Prediabetic State
sharing ipd: No