<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/NCT03785379</url>
  </required_header>
  <id_info>
    <org_study_id>2718P</org_study_id>
    <nct_id>NCT03785379</nct_id>
  </id_info>
  <brief_title>A Trial Evaluating the Effects of a One-year Lifestyle Intervention in Obese Patients With Type 2 Diabetes</brief_title>
  <official_title>A Randomized Trial Evaluating the Effects of One-Year Caloric Restriction and 12-Week Exercise Training Intervention in Obese Adults With Type 2 Diabetes: Emphasis on Metabolic Control and Resting Metabolic Rate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Padova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Padova</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Diabetic patients with uncontrolled disease are often characterized by increased energy&#xD;
      expenditure and could thus present a high resting metabolic rate (RMR). Lifestyle&#xD;
      interventions aimed at improving glucose control in these patients may lead to reductions of&#xD;
      futile pathways, resulting in lower rates of energy expenditure, and paradoxically to making&#xD;
      it more difficult to lose weight. However, only few studies investigated how exercise could&#xD;
      influence patients' RMR and results are still not unanimous. In this study, we aim to&#xD;
      investigate the effects on metabolic health of a combined dietary intervention and 12-week&#xD;
      exercise training in obese adults with type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although a number of exercise training interventions have been proposed to type 2 diabetes&#xD;
      patients, the current clinical practice demonstrates that most patients are still sedentary&#xD;
      and with excess body weight. A negative balance between energy intake and energy expenditure&#xD;
      is crucial to reduce excess body weight. However, diabetic patients with uncontrolled disease&#xD;
      are often characterized by increased energy expenditure and could thus present a high resting&#xD;
      metabolic rate (RMR). Lifestyle interventions aimed at improving glucose control in these&#xD;
      patients may lead to reductions of futile pathways, resulting in lower rates of energy&#xD;
      expenditure, and paradoxically to making it more difficult to lose weight. However, no robust&#xD;
      evidence has been collected on this issue, and the few studies that investigated how exercise&#xD;
      could influence patients' RMR have not shown unanimous results, especially concerning&#xD;
      combined dietary and physical activity interventions.&#xD;
&#xD;
      This open-label randomized trial in obese adults with type 2 diabetes aims to investigate the&#xD;
      effects of a 1-year caloric restriction and 12-week exercise training intervention on&#xD;
      metabolic health, RMR and VO2max.&#xD;
&#xD;
      In particular, eligible type 2 diabetes patients of our clinic will be invited to participate&#xD;
      in a short lifestyle intervention (LSI). LSI will consist of four weekly group-led lessons&#xD;
      lasting 60-90 minutes in which specialized professionals will educate patients on specific&#xD;
      dietary and physical activity recommendations for improving health and metabolic control.&#xD;
&#xD;
      After this month, patients will be randomly assigned either to: 1) 1-year caloric restriction&#xD;
      with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET&#xD;
      intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric&#xD;
      restriction with no exercise at health centers for 3 months and then a 12-week SSET from&#xD;
      month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity&#xD;
      will be unrestricted.&#xD;
&#xD;
      Type 2 diabetic and obese adult volunteers will be recruited and screened through medical&#xD;
      history, physical examination and biochemical analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2013</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 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>
    <intervention_model_description>After the baseline assessment, patients will be randomly assigned either to: 1) 1-year caloric restriction with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric restriction with no exercise at health centers for 3 months and then a 12-week SSET from month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity will be unrestricted.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline Glycated Hemoglobin (HbA1c) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Resting Metabolic Rate at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Resting Metabolic Rate at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Resting Metabolic Rate at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Body mass index at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Body mass index at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Body mass index at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Fat-free mass at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Fat-free mass at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Fat-free mass at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Fat mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline android to gynoid percent fat ratio at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline android to gynoid percent fat ratio at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline android to gynoid percent fat ratio at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline fasting plasma glucose at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline fasting plasma glucose at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline fasting plasma glucose at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline HDL cholesterol at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline HDL cholesterol at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline HDL cholesterol at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline total cholesterol at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline total cholesterol at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline total cholesterol at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline triglycerides levels at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline triglycerides levels at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline triglycerides levels at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline serum creatinine at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline serum creatinine at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline serum creatinine at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline urinary albumin-to-creatinine ratio at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline urinary albumin-to-creatinine ratio at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline urinary albumin-to-creatinine ratio at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline maximal aerobic power at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline maximal aerobic power at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline maximal aerobic power at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Glycated Hemoglobin (HbA1c) at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Glycated Hemoglobin (HbA1c) at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Caloric restriction and early SSET</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a caloric restriction and early exercise training (SSET) during the first 12-week, followed by no exercise at health centers for 3 months. Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Caloric restriction and late SSET</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a one-year caloric restriction with no exercise at health centers for 3 months, and then a 12-week exercise training (SSET). Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Caloric restriction</intervention_name>
    <description>A structured dietary training will be implemented to educate participants about recommended dietary habits.Patients will follow a caloric restriction (CR) diet, with an energy intake equal to the measured Resting Metabolic Rate (RMR) and with 45% carbohydrate, 20%protein, 35%fat, and 30 g/day fibers. At each follow-up, nutritionist will adjust CR to the latest measured RMR and assess the compliance to the diet.</description>
    <arm_group_label>Caloric restriction and early SSET</arm_group_label>
    <arm_group_label>Caloric restriction and late SSET</arm_group_label>
    <other_name>One-year caloric restriction</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise training</intervention_name>
    <description>Trainers will supervise participants during 12-weeks of structured exercise consisting of 150 min/week workouts, divided in three sessions of progressive mixed (aerobic and resistance) exercise. All aerobic exercise will be performed using treadmill and/or cycle ergo-meter.</description>
    <arm_group_label>Caloric restriction and early SSET</arm_group_label>
    <arm_group_label>Caloric restriction and late SSET</arm_group_label>
    <other_name>12-week structured supervised exercise training (SSET)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  age 30 to 64 years&#xD;
&#xD;
          -  less than 60 min aerobic exercise/week&#xD;
&#xD;
          -  absence of acute diseases&#xD;
&#xD;
          -  no current treatment with insulin or sulfonylureas&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI)&lt;28&#xD;
&#xD;
          -  HbA1c&lt;6%&#xD;
&#xD;
          -  Recent acute diseases, severe infections, trauma or surgery&#xD;
&#xD;
          -  Uncontrolled hypertension or hyperglycemia&#xD;
&#xD;
          -  Evidence of advanced cardiovascular, renal or hepatic diseases&#xD;
&#xD;
          -  Contraindication to exercise&#xD;
&#xD;
          -  Body weight change of more than 3% within the last 6 months&#xD;
&#xD;
          -  Medication changes within the last 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Zurlo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Padova</affiliation>
  </overall_official>
  <reference>
    <citation>Alawad AO, Merghani TH, Ballal MA. Resting metabolic rate in obese diabetic and obese non-diabetic subjects and its relation to glycaemic control. BMC Res Notes. 2013 Sep 26;6:382. doi: 10.1186/1756-0500-6-382.</citation>
    <PMID>24070224</PMID>
  </reference>
  <reference>
    <citation>Stevenson RW, Parsons JA, Alberti KG. Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs. Am J Physiol. 1983 Feb;244(2):E190-5. doi: 10.1152/ajpendo.1983.244.2.E190.</citation>
    <PMID>6337503</PMID>
  </reference>
  <reference>
    <citation>Zawadzki JK, Wolfe RR, Mott DM, Lillioja S, Howard BV, Bogardus C. Increased rate of Cori cycle in obese subjects with NIDDM and effect of weight reduction. Diabetes. 1988 Feb;37(2):154-9. doi: 10.2337/diab.37.2.154.</citation>
    <PMID>3391340</PMID>
  </reference>
  <reference>
    <citation>Piaggi P, Thearle MS, Bogardus C, Krakoff J. Fasting hyperglycemia predicts lower rates of weight gain by increased energy expenditure and fat oxidation rate. J Clin Endocrinol Metab. 2015 Mar;100(3):1078-87. doi: 10.1210/jc.2014-3582. Epub 2015 Jan 5.</citation>
    <PMID>25559400</PMID>
  </reference>
  <reference>
    <citation>Araiza P, Hewes H, Gashetewa C, Vella CA, Burge MR. Efficacy of a pedometer-based physical activity program on parameters of diabetes control in type 2 diabetes mellitus. Metabolism. 2006 Oct;55(10):1382-7. doi: 10.1016/j.metabol.2006.06.009.</citation>
    <PMID>16979410</PMID>
  </reference>
  <reference>
    <citation>Jennings AE, Alberga A, Sigal RJ, Jay O, Boule NG, Kenny GP. The effect of exercise training on resting metabolic rate in type 2 diabetes mellitus. Med Sci Sports Exerc. 2009 Aug;41(8):1558-65. doi: 10.1249/MSS.0b013e31819d6a6f.</citation>
    <PMID>19568205</PMID>
  </reference>
  <reference>
    <citation>Mourier A, Gautier JF, De Kerviler E, Bigard AX, Villette JM, Garnier JP, Duvallet A, Guezennec CY, Cathelineau G. Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements. Diabetes Care. 1997 Mar;20(3):385-91. doi: 10.2337/diacare.20.3.385.</citation>
    <PMID>9051392</PMID>
  </reference>
  <reference>
    <citation>Karstoft K, Brinklov CF, Thorsen IK, Nielsen JS, Ried-Larsen M. Resting Metabolic Rate Does Not Change in Response to Different Types of Training in Subjects with Type 2 Diabetes. Front Endocrinol (Lausanne). 2017 Jun 13;8:132. doi: 10.3389/fendo.2017.00132. eCollection 2017.</citation>
    <PMID>28659869</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>October 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>December 21, 2018</last_update_submitted>
  <last_update_submitted_qc>December 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Obesity</keyword>
  <keyword>Lifestyle intervention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT03785379
org study id: 2718P
nct id: NCT03785379
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Diabetic patients with uncontrolled disease are often characterized by increased energy
      expenditure and could thus present a high resting metabolic rate (RMR). Lifestyle
      interventions aimed at improving glucose control in these patients may lead to reductions of
      futile pathways, resulting in lower rates of energy expenditure, and paradoxically to making
      it more difficult to lose weight. However, only few studies investigated how exercise could
      influence patients' RMR and results are still not unanimous. In this study, we aim to
      investigate the effects on metabolic health of a combined dietary intervention and 12-week
      exercise training in obese adults with type 2 diabetes.
Although a number of exercise training interventions have been proposed to type 2 diabetes
      patients, the current clinical practice demonstrates that most patients are still sedentary
      and with excess body weight. A negative balance between energy intake and energy expenditure
      is crucial to reduce excess body weight. However, diabetic patients with uncontrolled disease
      are often characterized by increased energy expenditure and could thus present a high resting
      metabolic rate (RMR). Lifestyle interventions aimed at improving glucose control in these
      patients may lead to reductions of futile pathways, resulting in lower rates of energy
      expenditure, and paradoxically to making it more difficult to lose weight. However, no robust
      evidence has been collected on this issue, and the few studies that investigated how exercise
      could influence patients' RMR have not shown unanimous results, especially concerning
      combined dietary and physical activity interventions.

      This open-label randomized trial in obese adults with type 2 diabetes aims to investigate the
      effects of a 1-year caloric restriction and 12-week exercise training intervention on
      metabolic health, RMR and VO2max.

      In particular, eligible type 2 diabetes patients of our clinic will be invited to participate
      in a short lifestyle intervention (LSI). LSI will consist of four weekly group-led lessons
      lasting 60-90 minutes in which specialized professionals will educate patients on specific
      dietary and physical activity recommendations for improving health and metabolic control.

      After this month, patients will be randomly assigned either to: 1) 1-year caloric restriction
      with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET
      intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric
      restriction with no exercise at health centers for 3 months and then a 12-week SSET from
      month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity
      will be unrestricted.

      Type 2 diabetic and obese adult volunteers will be recruited and screened through medical
      history, physical examination and biochemical analyses.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: After the baseline assessment, patients will be randomly assigned either to: 1) 1-year caloric restriction with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric restriction with no exercise at health centers for 3 months and then a 12-week SSET from month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity will be unrestricted.
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline Glycated Hemoglobin (HbA1c) at 6 months
time frame: 6 months
description: Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.
measure: Change from baseline Resting Metabolic Rate at 3 months
time frame: 3 months
description: Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures
measure: Change from baseline Resting Metabolic Rate at 6 months
time frame: 6 months
description: Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures
measure: Change from baseline Resting Metabolic Rate at 12 months
time frame: 12 months
description: Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures
measure: Change from baseline Body mass index at 3 months
time frame: 3 months
description: Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.
measure: Change from baseline Body mass index at 6 months
time frame: 6 months
description: Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.
measure: Change from baseline Body mass index at 12 months
time frame: 12 months
description: Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared.
measure: Change from baseline Fat-free mass at 3 months
time frame: 3 months
description: Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline Fat-free mass at 6 months
time frame: 6 months
description: Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline Fat-free mass at 12 months
time frame: 12 months
description: Fat mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline android to gynoid percent fat ratio at 3 months
time frame: 3 months
description: Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline android to gynoid percent fat ratio at 6 months
time frame: 6 months
description: Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline android to gynoid percent fat ratio at 12 months
time frame: 12 months
description: Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.).
measure: Change from baseline fasting plasma glucose at 3 months
time frame: 3 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.
measure: Change from baseline fasting plasma glucose at 6 months
time frame: 6 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.
measure: Change from baseline fasting plasma glucose at 12 months
time frame: 12 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures.
measure: Change from baseline HDL cholesterol at 3 months
time frame: 3 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.
measure: Change from baseline HDL cholesterol at 6 months
time frame: 6 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.
measure: Change from baseline HDL cholesterol at 12 months
time frame: 12 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures.
measure: Change from baseline total cholesterol at 3 months
time frame: 3 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.
measure: Change from baseline total cholesterol at 6 months
time frame: 6 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.
measure: Change from baseline total cholesterol at 12 months
time frame: 12 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures.
measure: Change from baseline triglycerides levels at 3 months
time frame: 3 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.
measure: Change from baseline triglycerides levels at 6 months
time frame: 6 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.
measure: Change from baseline triglycerides levels at 12 months
time frame: 12 months
description: Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures.
measure: Change from baseline serum creatinine at 3 months
time frame: 3 months
description: Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.
measure: Change from baseline serum creatinine at 6 months
time frame: 6 months
description: Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.
measure: Change from baseline serum creatinine at 12 months
time frame: 12 months
description: Serum creatinine will be assessed from venous blood samples following standard quality-control procedures.
measure: Change from baseline urinary albumin-to-creatinine ratio at 3 months
time frame: 3 months
description: Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.
measure: Change from baseline urinary albumin-to-creatinine ratio at 6 months
time frame: 6 months
description: Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.
measure: Change from baseline urinary albumin-to-creatinine ratio at 12 months
time frame: 12 months
description: Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures.
measure: Change from baseline maximal aerobic power at 3 months
time frame: 3 months
description: VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.
measure: Change from baseline maximal aerobic power at 6 months
time frame: 6 months
description: VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.
measure: Change from baseline maximal aerobic power at 12 months
time frame: 12 months
description: VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol.
measure: Change from baseline Glycated Hemoglobin (HbA1c) at 3 months
time frame: 3 months
description: Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.
measure: Change from baseline Glycated Hemoglobin (HbA1c) at 12 months
time frame: 12 months
description: Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures.
arm group label: Caloric restriction and early SSET
arm group type: Active Comparator
description: Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a caloric restriction and early exercise training (SSET) during the first 12-week, followed by no exercise at health centers for 3 months. Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise.
arm group label: Caloric restriction and late SSET
arm group type: Active Comparator
description: Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a one-year caloric restriction with no exercise at health centers for 3 months, and then a 12-week exercise training (SSET). Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise.
intervention type: Behavioral
intervention name: Caloric restriction
description: A structured dietary training will be implemented to educate participants about recommended dietary habits.Patients will follow a caloric restriction (CR) diet, with an energy intake equal to the measured Resting Metabolic Rate (RMR) and with 45% carbohydrate, 20%protein, 35%fat, and 30 g/day fibers. At each follow-up, nutritionist will adjust CR to the latest measured RMR and assess the compliance to the diet.
arm group label: Caloric restriction and early SSET
arm group label: Caloric restriction and late SSET
other name: One-year caloric restriction
intervention type: Behavioral
intervention name: Exercise training
description: Trainers will supervise participants during 12-weeks of structured exercise consisting of 150 min/week workouts, divided in three sessions of progressive mixed (aerobic and resistance) exercise. All aerobic exercise will be performed using treadmill and/or cycle ergo-meter.
arm group label: Caloric restriction and early SSET
arm group label: Caloric restriction and late SSET
other name: 12-week structured supervised exercise training (SSET)
criteria: 
gender: All
minimum age: 30 Years
maximum age: 64 Years
healthy volunteers: No
last name: Francesco Zurlo, MD
role: Principal Investigator
affiliation: University of Padova
citation: Alawad AO, Merghani TH, Ballal MA. Resting metabolic rate in obese diabetic and obese non-diabetic subjects and its relation to glycaemic control. BMC Res Notes. 2013 Sep 26;6:382. doi: 10.1186/1756-0500-6-382.
PMID: 24070224
citation: Stevenson RW, Parsons JA, Alberti KG. Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs. Am J Physiol. 1983 Feb;244(2):E190-5. doi: 10.1152/ajpendo.1983.244.2.E190.
PMID: 6337503
citation: Zawadzki JK, Wolfe RR, Mott DM, Lillioja S, Howard BV, Bogardus C. Increased rate of Cori cycle in obese subjects with NIDDM and effect of weight reduction. Diabetes. 1988 Feb;37(2):154-9. doi: 10.2337/diab.37.2.154.
PMID: 3391340
citation: Piaggi P, Thearle MS, Bogardus C, Krakoff J. Fasting hyperglycemia predicts lower rates of weight gain by increased energy expenditure and fat oxidation rate. J Clin Endocrinol Metab. 2015 Mar;100(3):1078-87. doi: 10.1210/jc.2014-3582. Epub 2015 Jan 5.
PMID: 25559400
citation: Araiza P, Hewes H, Gashetewa C, Vella CA, Burge MR. Efficacy of a pedometer-based physical activity program on parameters of diabetes control in type 2 diabetes mellitus. Metabolism. 2006 Oct;55(10):1382-7. doi: 10.1016/j.metabol.2006.06.009.
PMID: 16979410
citation: Jennings AE, Alberga A, Sigal RJ, Jay O, Boule NG, Kenny GP. The effect of exercise training on resting metabolic rate in type 2 diabetes mellitus. Med Sci Sports Exerc. 2009 Aug;41(8):1558-65. doi: 10.1249/MSS.0b013e31819d6a6f.
PMID: 19568205
citation: Mourier A, Gautier JF, De Kerviler E, Bigard AX, Villette JM, Garnier JP, Duvallet A, Guezennec CY, Cathelineau G. Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements. Diabetes Care. 1997 Mar;20(3):385-91. doi: 10.2337/diacare.20.3.385.
PMID: 9051392
citation: Karstoft K, Brinklov CF, Thorsen IK, Nielsen JS, Ried-Larsen M. Resting Metabolic Rate Does Not Change in Response to Different Types of Training in Subjects with Type 2 Diabetes. Front Endocrinol (Lausanne). 2017 Jun 13;8:132. doi: 10.3389/fendo.2017.00132. eCollection 2017.
PMID: 28659869
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No