<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/NCT02988011</url>
  </required_header>
  <id_info>
    <org_study_id>CRUDOS AZSciLife</org_study_id>
    <nct_id>NCT02988011</nct_id>
  </id_info>
  <brief_title>Improving Glucose and Lipid Metabolism Through Caloric Restriction Using Diet or Surgery (CRUDOS)</brief_title>
  <acronym>CRUDOS</acronym>
  <official_title>Influence of Weight Loss by Diet and Surgery on Metabolomic Profile, Body Composition, and Tissue Specific Glucose Uptake: Insights in Type 2 Diabetes Regression (CRUDOS Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this explorative randomized clinical study, the investigators aim to study metabolic,&#xD;
      cellular, and molecular changes that occur during weight loss in obese subjects with and&#xD;
      without type 2 diabetes. Using novel &quot;imiomics&quot; (imaging technique using PET/MR&#xD;
      bioinformatics) analyses to examine possible metabolic differences between energy restricted&#xD;
      diet and gastric by-pass surgery on whole-body and tissue specific insulin sensitivity,&#xD;
      glucose tolerance, metabolite and protein profiles, fatty acid metabolism, ectopic fat&#xD;
      content, and gene expression in adipose tissue. This study aims to identify novel biomarkers&#xD;
      and drug targets for type 2 diabetes as well as validate promising and established biomarkers&#xD;
      in an interventional model for improved glucose metabolism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      By using omics platforms such as genomics, proteomics and metabolomics we can have large&#xD;
      amount of information about metabolic changes at both tissue and whole body level. In&#xD;
      parallel to this, clinical imaging modalities such as Magnetic Resonance Imaging (MRI) and&#xD;
      Positron Emission Tomography (PET) have developed rapidly, allowing for whole-body studies of&#xD;
      how different tissues are involved in systemic diseases. Furthermore, new hybrid systems such&#xD;
      as integrated PET-MRI provide combined information of human morphology and function. The&#xD;
      integration of PET with MRI reduces the radiation dose compared with PET-CT to acceptable&#xD;
      levels for metabolic studies. To handle the large amounts of data from these examinations we&#xD;
      are currently developing an image analysis concept, &quot;Imiomics&quot;, that allows holistic analysis&#xD;
      of whole-body imaging data with integration of non-imaging data. In the current study, we&#xD;
      plan to use PET-MRI as well as imiomics methodology, together with gold standard methodology&#xD;
      to assess insulin sensitivity and glucose tolerance in vivo. We aim to conduct a randomized&#xD;
      study (CRUDOS study; Caloric Restriction Using Diet Or Surgery) to study glycometabolic&#xD;
      effects before and after gastric bypass surgery and low-calorie diet in subjects at different&#xD;
      stages of glucose tolerance (i.e. obese subjects with and without T2D).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 28, 2016</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner</measure>
    <time_frame>4 weeks</time_frame>
    <description>Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolite concentrations in plasma</measure>
    <time_frame>4 weeks</time_frame>
    <description>Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gene expression in adipose tissue</measure>
    <time_frame>4 weeks</time_frame>
    <description>Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lipoprotein changes in plasma assessed by routine clinical chemistry</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma adipokines (e.g. adiponectin) assessed by elisa</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatty acid composition in plasma assessed by gas chromatography</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma protein profile (proteomics) assessed by immunohistochemistry</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epigenetic changes assessed as DNA methylation</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Type2 Diabetes</condition>
  <condition>Weight Loss</condition>
  <condition>Insulin Sensitivity</condition>
  <condition>Metabolism and Nutrition Disorder</condition>
  <condition>Metabolism Disorder, Glucose</condition>
  <condition>Bariatric Surgery Candidate</condition>
  <arm_group>
    <arm_group_label>Gastric by-pass surgery</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gastric by-pass surgery without prior low-caloric diet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-caloric diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Low-caloric diet followed by gastric by-pass surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gastric by-pass surgery</intervention_name>
    <description>Gastric by-pass surgery is expected to achieve a mean weight loss of 7-8kg in 4 weeks, which is similar weight-loss achieved in the other arm (low-caloric diet) during this time period.</description>
    <arm_group_label>Gastric by-pass surgery</arm_group_label>
    <arm_group_label>Low-caloric diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Low-caloric diet</intervention_name>
    <description>Energy restricted diet with a total energy intake of 800-1200kcal/day</description>
    <arm_group_label>Low-caloric diet</arm_group_label>
    <other_name>Energy restricted diet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18-60 years&#xD;
&#xD;
          -  BMI 35-45&#xD;
&#xD;
          -  Sagittal abdominal diameter ≤38.5cm&#xD;
&#xD;
          -  For participants with type 2 Diabetes Mellitus, a disease duration of no more than 10&#xD;
             years, treated with 0-3 oral antidiabetic drugs and/or with diet. HbA1C 48-80mmol/mol&#xD;
             at baseline visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes complications: proliferative retinopathy, maculopathy, chronic renal failure&#xD;
             stadium 3 with an eGFR&lt;60, foot ulcers, symptomatic neuropathy&#xD;
&#xD;
          -  Medications within 3 months: Insulin, Thiazolidinediones&#xD;
&#xD;
          -  Any other condition with in the opinion of the investigator would render the&#xD;
             participant unsuitable for inclusion in the study and /or for the patients safety&#xD;
&#xD;
          -  Judgment by the investigator that the subject should not participate in the study if&#xD;
             considers subject unlikely to comply with study procedures, restrictions and&#xD;
             requirements&#xD;
&#xD;
          -  Pregnant or planning to be pregnant during the study.&#xD;
&#xD;
          -  Known or suspected history of significant drug abuse.&#xD;
&#xD;
          -  History of alcohol abuse or excessive intake of alcohol as judged by investigator.&#xD;
&#xD;
          -  History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as&#xD;
             judged by the investigator&#xD;
&#xD;
          -  Sleep apnoea&#xD;
&#xD;
          -  Any previous serious cardiovascular event, stroke, acute myocardial infarction.&#xD;
&#xD;
          -  Any condition when MRI-PET is contraindicated such as, but not limited to, having a&#xD;
             pacemaker or claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulf Riserus, MMed, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Magnus Sundbom, MD, PhD</last_name>
    <phone>+46186114616</phone>
    <email>magnus.sundbom@surgsci.uu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ulf Riserus, PhD</last_name>
    <phone>+46186117971</phone>
    <email>ulf.riserus@pubcare.uu.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Uppsala univeristy hospital</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>October 25, 2017</last_update_submitted>
  <last_update_submitted_qc>October 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Uppsala University</investigator_affiliation>
    <investigator_full_name>Ulf Risérus</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>type 2 diabetes</keyword>
  <keyword>gastric by-pass surgery</keyword>
  <keyword>low calorie diet</keyword>
  <keyword>glucose metabolism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Nutrition Disorders</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</mesh_term>
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Most of the data is planned to be shared after the study has ended, the date for when this will occur however needs to be decided.</ipd_description>
  </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/NCT02988011
org study id: CRUDOS AZSciLife
nct id: NCT02988011
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this explorative randomized clinical study, the investigators aim to study metabolic,
      cellular, and molecular changes that occur during weight loss in obese subjects with and
      without type 2 diabetes. Using novel "imiomics" (imaging technique using PET/MR
      bioinformatics) analyses to examine possible metabolic differences between energy restricted
      diet and gastric by-pass surgery on whole-body and tissue specific insulin sensitivity,
      glucose tolerance, metabolite and protein profiles, fatty acid metabolism, ectopic fat
      content, and gene expression in adipose tissue. This study aims to identify novel biomarkers
      and drug targets for type 2 diabetes as well as validate promising and established biomarkers
      in an interventional model for improved glucose metabolism.
By using omics platforms such as genomics, proteomics and metabolomics we can have large
      amount of information about metabolic changes at both tissue and whole body level. In
      parallel to this, clinical imaging modalities such as Magnetic Resonance Imaging (MRI) and
      Positron Emission Tomography (PET) have developed rapidly, allowing for whole-body studies of
      how different tissues are involved in systemic diseases. Furthermore, new hybrid systems such
      as integrated PET-MRI provide combined information of human morphology and function. The
      integration of PET with MRI reduces the radiation dose compared with PET-CT to acceptable
      levels for metabolic studies. To handle the large amounts of data from these examinations we
      are currently developing an image analysis concept, "Imiomics", that allows holistic analysis
      of whole-body imaging data with integration of non-imaging data. In the current study, we
      plan to use PET-MRI as well as imiomics methodology, together with gold standard methodology
      to assess insulin sensitivity and glucose tolerance in vivo. We aim to conduct a randomized
      study (CRUDOS study; Caloric Restriction Using Diet Or Surgery) to study glycometabolic
      effects before and after gastric bypass surgery and low-calorie diet in subjects at different
      stages of glucose tolerance (i.e. obese subjects with and without T2D).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner
time frame: 4 weeks
description: Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.
measure: Metabolite concentrations in plasma
time frame: 4 weeks
description: Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry
measure: Gene expression in adipose tissue
time frame: 4 weeks
description: Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses
measure: Lipoprotein changes in plasma assessed by routine clinical chemistry
time frame: 4 weeks
measure: Plasma adipokines (e.g. adiponectin) assessed by elisa
time frame: 4 weeks
measure: Fatty acid composition in plasma assessed by gas chromatography
time frame: 4 weeks
measure: Changes in plasma protein profile (proteomics) assessed by immunohistochemistry
time frame: 4 weeks
measure: Epigenetic changes assessed as DNA methylation
time frame: 4 weeks
arm group label: Gastric by-pass surgery
arm group type: Active Comparator
description: Gastric by-pass surgery without prior low-caloric diet
arm group label: Low-caloric diet
arm group type: Active Comparator
description: Low-caloric diet followed by gastric by-pass surgery
intervention type: Procedure
intervention name: Gastric by-pass surgery
description: Gastric by-pass surgery is expected to achieve a mean weight loss of 7-8kg in 4 weeks, which is similar weight-loss achieved in the other arm (low-caloric diet) during this time period.
arm group label: Gastric by-pass surgery
arm group label: Low-caloric diet
intervention type: Dietary Supplement
intervention name: Low-caloric diet
description: Energy restricted diet with a total energy intake of 800-1200kcal/day
arm group label: Low-caloric diet
other name: Energy restricted diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ulf Riserus, MMed, PhD
role: Principal Investigator
affiliation: Uppsala University
last name: Magnus Sundbom, MD, PhD
phone: +46186114616
email: magnus.sundbom@surgsci.uu.se
last name: Ulf Riserus, PhD
phone: +46186117971
email: ulf.riserus@pubcare.uu.se
facility: 
status: Recruiting
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Uppsala University
investigator full name: Ulf Risérus
investigator title: Associate professor
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Metabolic Diseases
mesh term: Nutrition Disorders
mesh term: Glucose Metabolism Disorders
mesh term: Weight Loss
sharing ipd: Undecided
ipd description: Most of the data is planned to be shared after the study has ended, the date for when this will occur however needs to be decided.