<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/NCT03796000</url>
  </required_header>
  <id_info>
    <org_study_id>2018-00712</org_study_id>
    <secondary_id>2018-00712</secondary_id>
    <nct_id>NCT03796000</nct_id>
  </id_info>
  <brief_title>Characterization of Human Intestinal Macrophages in Metabolic Disease</brief_title>
  <acronym>iMAC</acronym>
  <official_title>Characterization of Human Intestinal Macrophages in Metabolic Disease - iMAC (Pilot) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</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>
      This is a prospective, observational study aiming at improving the understanding of the&#xD;
      pathophysiology of metabolic disease. As inflammation has been recognized as a key&#xD;
      characteristic of metabolic disease but its starting point is still unknown, the&#xD;
      investigators' aim is to characterize intestinal macrophages from human gut biopsies taken in&#xD;
      diagnostic endoscopies of the gastrointestinal tract or in bariatric surgeries for clinical&#xD;
      reasons.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Metabolic disease including obesity and diabetes has reached epidemic proportions in the past&#xD;
      years. Besides classical risk factors such as unhealthy diet and physical inactivity, smoking&#xD;
      and air pollution have also emerged as unexpected risk factors for type 2 Diabetes.&#xD;
&#xD;
      Inflammation has been reported as key characteristic of metabolic disease and is predictive&#xD;
      of future cardiovascular events. However, the starting point of chronic low-grade&#xD;
      inflammation is not known.&#xD;
&#xD;
      As the gastrointestinal tract first comes into contact with dietary components, but&#xD;
      potentially also air pollution/ smoke particles ingested upon mucociliary clearance from the&#xD;
      lung, the gut could be the starting point of inflammation in metabolic disease.&#xD;
&#xD;
      The aim of this study is to characterize intestinal macrophages in obese versus lean subjects&#xD;
      and smokers versus non-smokers to translate the principal investigator's preclinical findings&#xD;
      to human disease and assess whether an inflammatory shift prevails in human intestinal&#xD;
      macrophages in metabolic disease. Additionally, to assess whether intestinal macrophage&#xD;
      subpopulations can be altered deliberately by nutritional intervention, the investigators&#xD;
      will assess intestinal macrophages from subjects scheduled for bariatric surgery that will be&#xD;
      on a calorie-restricted diet during the last 2 to 4 weeks prior to surgery.&#xD;
&#xD;
      The macrophages originate from human gut samples. As patients will undergo diagnostic&#xD;
      endoscopy of the gastrointestinal tract or bariatric surgery for clinical reasons and the&#xD;
      standard of care will not be changed by the study, there will be no additional interventions&#xD;
      to patients by their participation in the study. Additionally, three EDTA and one serum blood&#xD;
      tube for the analysis of inflammatory cells and markers in the blood will be taken as well as&#xD;
      a single stool sample. The investigators' goal is to recruit in total 150 patients as it will&#xD;
      be a pilot study in a first step.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 14, 2018</start_date>
  <completion_date type="Actual">May 14, 2022</completion_date>
  <primary_completion_date type="Actual">April 14, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of intestinal macrophages</measure>
    <time_frame>2 years</time_frame>
    <description>Quantity (absolute and relative numbers) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Type and rate of subpopulations of intestinal macrophages</measure>
    <time_frame>2 years</time_frame>
    <description>Quality (inflammatory versus non-inflammatory subpopulations) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of other intestinal immune cells</measure>
    <time_frame>2 years</time_frame>
    <description>In case the investigators do not find clear differences in frequency of intestinal macrophages, they will assess other intestinal immune cells (e.g. B-, T-lymphocytes), and enteroendocrine cells (e.g. L-cells) as a secondary endpoint in an explorative manner. Additionally, the investigators aim to correlate their findings from the biopsy samples with inflammation markers and immune cells in the blood, with microbiota and immune cells in the stool and with the eating habits of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type and rate of subpopulations of other intestinal immune cells</measure>
    <time_frame>2 years</time_frame>
    <description>In case the investigators do not find clear differences in subpopulations of intestinal macrophages, they will assess other intestinal immune cells (e.g. B-, T-lymphocytes), and enteroendocrine cells (e.g. L-cells) as a secondary endpoint in an explorative manner. Additionally, the investigators aim to correlate their findings from the biopsy samples with inflammation markers and immune cells in the blood, with microbiota and immune cells in the stool and with the eating habits of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profile of intestinal macrophages</measure>
    <time_frame>2 years</time_frame>
    <description>Gene expression of intestinal macrophages in biopsies from the colon in obese versus lean non-smokers by RNA sequencing.</description>
  </secondary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">54</enrollment>
  <condition>Metabolic Disease</condition>
  <arm_group>
    <arm_group_label>colonoscopy: obese and smoker</arm_group_label>
    <description>10 small tissue samples of the Colon transversum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample</description>
  </arm_group>
  <arm_group>
    <arm_group_label>colonoscopy: obese and non-smoker</arm_group_label>
    <description>10 small tissue samples of the Colon transversum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample</description>
  </arm_group>
  <arm_group>
    <arm_group_label>colonoscopy: lean and smoker</arm_group_label>
    <description>10 small tissue samples of the Colon transversum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample</description>
  </arm_group>
  <arm_group>
    <arm_group_label>colonoscopy: lean and non-smoker</arm_group_label>
    <description>10 small tissue samples of the Colon transversum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample</description>
  </arm_group>
  <arm_group>
    <arm_group_label>gastroscopy: obese and non-smoker undergoing bariatric surgery</arm_group_label>
    <description>6 small tissue samples of the gastric corpus and 6 of the Duodenum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample&#xD;
1cm long piece of the jejunum, which is usually disposed during bariatric surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>gastroscopy: lean and non-smoker</arm_group_label>
    <description>6 small tissue samples of the gastric corpus and 6 of the Duodenum&#xD;
3 EDTA blood samples and 1 Serum blood sample&#xD;
in some cases 1 single stool sample</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>tissue samples, blood and stool sample</intervention_name>
    <description>Tissue samples from gastroscopy/colonoscopy.</description>
    <arm_group_label>colonoscopy: lean and non-smoker</arm_group_label>
    <arm_group_label>colonoscopy: lean and smoker</arm_group_label>
    <arm_group_label>colonoscopy: obese and non-smoker</arm_group_label>
    <arm_group_label>colonoscopy: obese and smoker</arm_group_label>
    <arm_group_label>gastroscopy: lean and non-smoker</arm_group_label>
    <arm_group_label>gastroscopy: obese and non-smoker undergoing bariatric surgery</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All patients planned for diagnostic endoscopy of the gastrointestinal tract or bariatric&#xD;
        surgery at the University Hospital of Basel, the doctor's Office MagenDarm Basel or the&#xD;
        Department of Visceral Surgery, Hospital Lindenhof of Bern will be screened for study&#xD;
        participation, contacted and informed about the study if suitable to all inclusion and&#xD;
        exclusion criterias.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient undergoing colonoscopy:&#xD;
&#xD;
          -  Obese (BMI &gt; 32 kg/m2 ) and smoker (≥ 1 pack cigarettes/d)&#xD;
&#xD;
          -  Obese (BMI &gt; 32 kg/m2 ) and non-smoker (control group)&#xD;
&#xD;
          -  Lean (BMI &lt; 27 kg/m2 ) and smoker (≥ 1 pack cigarettes/d)&#xD;
&#xD;
          -  Lean (BMI &lt; 27 kg/m2 ) and non-smoker (control group)&#xD;
&#xD;
        Patient undergoing gastroscopy:&#xD;
&#xD;
          -  Obese (BMI &gt; 35 kg/m2 ) and non-smoker planned for bariatric surgery&#xD;
&#xD;
          -  Lean (BMI &lt; 27 kg/m2 ) and non-smoker (control group)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to provide informed consent, e.g. mental impairment or insufficient&#xD;
             knowledge of project language&#xD;
&#xD;
          -  Intake of corticosteroids&#xD;
&#xD;
          -  Anti-inflammatory/ immunosuppressive drugs&#xD;
&#xD;
          -  Clinical signs of current infection&#xD;
&#xD;
          -  Known anemia (e.g. hemoglobin &lt; 110 g/L for males, &lt; 100 g/L for females)&#xD;
&#xD;
          -  Known neutropenia (e.g. leukocyte count &lt; 1.5 × 10^9/L or ANC &lt; 0.5 × 10^9/L)&#xD;
&#xD;
          -  Known immunodeficiency, e.g. HIV&#xD;
&#xD;
          -  Known vasculitis, collagenosis&#xD;
&#xD;
          -  Known inflammatory bowel disease&#xD;
&#xD;
          -  Known adrenal insufficiency and/or substitution with glucocorticoids&#xD;
&#xD;
          -  Known clinically significant kidney or liver disease (e.g. creatinine &gt; 1.5 mg/dL,&#xD;
             AST/ALT &gt; 2 × ULN, alkaline phosphatase &gt; 2 × ULN, or total bilirubin [tBili] &gt; 1.5 ×&#xD;
             ULN)&#xD;
&#xD;
          -  Risky daily alcohol consumption (&gt; 24g/d for males, &gt; 12g for females), known liver&#xD;
             cirrhosis Child B or C&#xD;
&#xD;
          -  Known uncontrolled congestive heart failure&#xD;
&#xD;
          -  Known uncontrolled malignant disease&#xD;
&#xD;
          -  Currently pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claudia Cavelti-Weder, PD Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Basel</name>
      <address>
        <city>Basel</city>
        <state>Baselstadt</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>June 22, 2022</last_update_submitted>
  <last_update_submitted_qc>June 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Basel, Switzerland</investigator_affiliation>
    <investigator_full_name>Claudia Cavelti</investigator_full_name>
    <investigator_title>private lecturer</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03796000/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03796000
org study id: 2018-00712
secondary id: 2018-00712
nct id: NCT03796000
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a prospective, observational study aiming at improving the understanding of the
      pathophysiology of metabolic disease. As inflammation has been recognized as a key
      characteristic of metabolic disease but its starting point is still unknown, the
      investigators' aim is to characterize intestinal macrophages from human gut biopsies taken in
      diagnostic endoscopies of the gastrointestinal tract or in bariatric surgeries for clinical
      reasons.
Metabolic disease including obesity and diabetes has reached epidemic proportions in the past
      years. Besides classical risk factors such as unhealthy diet and physical inactivity, smoking
      and air pollution have also emerged as unexpected risk factors for type 2 Diabetes.

      Inflammation has been reported as key characteristic of metabolic disease and is predictive
      of future cardiovascular events. However, the starting point of chronic low-grade
      inflammation is not known.

      As the gastrointestinal tract first comes into contact with dietary components, but
      potentially also air pollution/ smoke particles ingested upon mucociliary clearance from the
      lung, the gut could be the starting point of inflammation in metabolic disease.

      The aim of this study is to characterize intestinal macrophages in obese versus lean subjects
      and smokers versus non-smokers to translate the principal investigator's preclinical findings
      to human disease and assess whether an inflammatory shift prevails in human intestinal
      macrophages in metabolic disease. Additionally, to assess whether intestinal macrophage
      subpopulations can be altered deliberately by nutritional intervention, the investigators
      will assess intestinal macrophages from subjects scheduled for bariatric surgery that will be
      on a calorie-restricted diet during the last 2 to 4 weeks prior to surgery.

      The macrophages originate from human gut samples. As patients will undergo diagnostic
      endoscopy of the gastrointestinal tract or bariatric surgery for clinical reasons and the
      standard of care will not be changed by the study, there will be no additional interventions
      to patients by their participation in the study. Additionally, three EDTA and one serum blood
      tube for the analysis of inflammatory cells and markers in the blood will be taken as well as
      a single stool sample. The investigators' goal is to recruit in total 150 patients as it will
      be a pilot study in a first step.
observational model: Cohort
time perspective: Prospective
measure: Number of intestinal macrophages
time frame: 2 years
description: Quantity (absolute and relative numbers) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.
measure: Type and rate of subpopulations of intestinal macrophages
time frame: 2 years
description: Quality (inflammatory versus non-inflammatory subpopulations) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.
measure: Number of other intestinal immune cells
time frame: 2 years
description: In case the investigators do not find clear differences in frequency of intestinal macrophages, they will assess other intestinal immune cells (e.g. B-, T-lymphocytes), and enteroendocrine cells (e.g. L-cells) as a secondary endpoint in an explorative manner. Additionally, the investigators aim to correlate their findings from the biopsy samples with inflammation markers and immune cells in the blood, with microbiota and immune cells in the stool and with the eating habits of the patients.
measure: Type and rate of subpopulations of other intestinal immune cells
time frame: 2 years
description: In case the investigators do not find clear differences in subpopulations of intestinal macrophages, they will assess other intestinal immune cells (e.g. B-, T-lymphocytes), and enteroendocrine cells (e.g. L-cells) as a secondary endpoint in an explorative manner. Additionally, the investigators aim to correlate their findings from the biopsy samples with inflammation markers and immune cells in the blood, with microbiota and immune cells in the stool and with the eating habits of the patients.
measure: Gene expression profile of intestinal macrophages
time frame: 2 years
description: Gene expression of intestinal macrophages in biopsies from the colon in obese versus lean non-smokers by RNA sequencing.
arm group label: colonoscopy: obese and smoker
description: 10 small tissue samples of the Colon transversum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
arm group label: colonoscopy: obese and non-smoker
description: 10 small tissue samples of the Colon transversum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
arm group label: colonoscopy: lean and smoker
description: 10 small tissue samples of the Colon transversum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
arm group label: colonoscopy: lean and non-smoker
description: 10 small tissue samples of the Colon transversum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
arm group label: gastroscopy: obese and non-smoker undergoing bariatric surgery
description: 6 small tissue samples of the gastric corpus and 6 of the Duodenum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
1cm long piece of the jejunum, which is usually disposed during bariatric surgery.
arm group label: gastroscopy: lean and non-smoker
description: 6 small tissue samples of the gastric corpus and 6 of the Duodenum
3 EDTA blood samples and 1 Serum blood sample
in some cases 1 single stool sample
intervention type: Procedure
intervention name: tissue samples, blood and stool sample
description: Tissue samples from gastroscopy/colonoscopy.
arm group label: colonoscopy: lean and non-smoker
arm group label: colonoscopy: lean and smoker
arm group label: colonoscopy: obese and non-smoker
arm group label: colonoscopy: obese and smoker
arm group label: gastroscopy: lean and non-smoker
arm group label: gastroscopy: obese and non-smoker undergoing bariatric surgery
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Claudia Cavelti-Weder, PD Dr. med.
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Basel, Switzerland
investigator full name: Claudia Cavelti
investigator title: private lecturer
mesh term: Metabolic Diseases
sharing ipd: No
provided document: 