<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/NCT01686568</url>
  </required_header>
  <id_info>
    <org_study_id>12-004590</org_study_id>
    <secondary_id>KL2TR000136</secondary_id>
    <secondary_id>U24DK100469</secondary_id>
    <secondary_id>DK50456</secondary_id>
    <secondary_id>DK40484</secondary_id>
    <secondary_id>5T32DK007352</secondary_id>
    <secondary_id>5UL1TR000135</secondary_id>
    <nct_id>NCT01686568</nct_id>
  </id_info>
  <brief_title>Omega-3 Fatty Acids and Insulin Sensitivity</brief_title>
  <official_title>Dietary Omega-3 Fatty Acids as a Therapeutic Strategy in Insulin Resistant Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Building Interdisciplinary Research Careers in Women's Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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>
      This study is being done to understand the effects of dietary omega-3 fats on insulin&#xD;
      sensitivity in adult men and women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid&#xD;
      (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents,&#xD;
      but data in humans is ambiguous. No existing studies have systematically evaluated the&#xD;
      influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant,&#xD;
      non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of&#xD;
      purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin&#xD;
      sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals.&#xD;
      Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase&#xD;
      the content and function of mitochondria in skeletal muscle, measured using a combination of&#xD;
      in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA&#xD;
      supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant&#xD;
      humans, and this improvement will be associated with mitochondrial biogenesis and attenuated&#xD;
      lipid accumulation in skeletal muscle and liver.&#xD;
&#xD;
      A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo&#xD;
      supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content&#xD;
      of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry),&#xD;
      crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining),&#xD;
      as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor&#xD;
      ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress&#xD;
      palmitate flux by 50% (IC50(palmitate)f).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 21, 2012</start_date>
  <completion_date type="Actual">June 8, 2015</completion_date>
  <primary_completion_date type="Actual">October 30, 2014</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up</measure>
    <time_frame>Baseline, after 6 months of treatment</time_frame>
    <description>A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up</measure>
    <time_frame>baseline, after 6 months of treatment</time_frame>
    <description>Following consumption of a mixed meal, beta cell function will be evaluated from serial measurements of C-peptide. C-peptide was measured using a two-side immunometric assay using electrochemiluminescence detection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up</measure>
    <time_frame>Baseline, after 6 months of treatment</time_frame>
    <description>Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)</measure>
    <time_frame>approximately after 6 months of treatment</time_frame>
    <description>Sensitivity of adipose tissue lipolysis to insulin suppression, was calculated as the insulin concentration needed to suppress palmitate appearance rates (ie, flux) by 50% (IC50(palmitate)f).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Senescent Cells</measure>
    <time_frame>approximately after 6 months of treatment</time_frame>
    <description>Tissue burden of senescent cells, which was measured by staining for senescence-associated B-galactosidase activity and expressed as the number per 100 nucleated positive cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunohistochemistry Assessments of Macrophage Burden</measure>
    <time_frame>approximately after 6 months of treatment</time_frame>
    <description>One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess macrophage burden (total (CD68), M1 (CD14) and M2 (CD206) macrophages per 100 adipocytes).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrophage Crown-like Structures</measure>
    <time_frame>approximately after 6 months of treatment</time_frame>
    <description>Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs). One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess the number of crown-like structures per 10 images.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Omega-3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omega-3</intervention_name>
    <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
    <arm_group_label>Omega-3</arm_group_label>
    <other_name>Essential fatty acids</other_name>
    <other_name>Omega-3 fatty acids</other_name>
    <other_name>Omega-3 polyunsaturated fatty acids</other_name>
    <other_name>PUFAs</other_name>
    <other_name>Lovaza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Age 18-65 years&#xD;
&#xD;
          2. Insulin resistant (Homeostasis Model Assessment (HOMA) Insulin Resistance (IR) ≥2.6)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Current use of omega-3 nutritional supplements&#xD;
&#xD;
          2. Fasting plasma glucose ≥126 mg/dL&#xD;
&#xD;
          3. Active coronary artery disease&#xD;
&#xD;
          4. Participation in structured exercise (&gt;2 times per week for 30 minutes or longer)&#xD;
&#xD;
          5. Smoking&#xD;
&#xD;
          6. Medications known to affect muscle metabolism (e.g., beta blockers, corticosteroids,&#xD;
             tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, anticoagulants)&#xD;
&#xD;
          7. Renal failure (serum creatinine &gt; 1.5mg/dl)&#xD;
&#xD;
          8. Chronic active liver disease (AST&gt;144 IU/L and alanine transaminase (ALT)&gt;165 IU/L)&#xD;
&#xD;
          9. Anti-coagulant therapy (warfarin/heparin)&#xD;
&#xD;
         10. International normalized ratio (INR) &gt;3&#xD;
&#xD;
         11. Use of systemic glucocorticoids&#xD;
&#xD;
         12. Chronic use of NSAIDS or aspirin&#xD;
&#xD;
         13. Pregnancy or breastfeeding&#xD;
&#xD;
         14. Alcohol consumption greater than 2 glasses/day&#xD;
&#xD;
         15. Hypothyroidism&#xD;
&#xD;
         16. Fish or shellfish allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian Lanza, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Lalia AZ, Johnson ML, Jensen MD, Hames KC, Port JD, Lanza IR. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans. Diabetes Care. 2015 Jul;38(7):1228-37. doi: 10.2337/dc14-3101. Epub 2015 Apr 7.</citation>
    <PMID>25852206</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <results_first_submitted>June 16, 2015</results_first_submitted>
  <results_first_submitted_qc>June 16, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 10, 2015</results_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Ian R. Lanza</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from the Mayo Clinic in Rochester, Minnesota.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Omega-3</title>
          <description>Patients in this group will receive oral supplementation with EPA + Docosahexaenoic acid (DHA) (3.9grams/day) for 6 months.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Main Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliance with protocol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Liver enzymes above range of exclusion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Sub-Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not consented for sub-study</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics were reported for participants who received treatment and did not withdraw from the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Omega-3</title>
          <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.3" spread="2.9"/>
                    <measurement group_id="B2" value="32.6" spread="2.5"/>
                    <measurement group_id="B3" value="34.1" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up</title>
        <description>A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.</description>
        <time_frame>Baseline, after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up</title>
          <description>A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.</description>
          <units>mg/kg FFM/min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.92" spread="1.04"/>
                    <measurement group_id="O2" value="10.39" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Month Follow Up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.16" spread="1.02"/>
                    <measurement group_id="O2" value="10.80" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up</title>
        <description>Following consumption of a mixed meal, beta cell function will be evaluated from serial measurements of C-peptide. C-peptide was measured using a two-side immunometric assay using electrochemiluminescence detection.</description>
        <time_frame>baseline, after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up</title>
          <description>Following consumption of a mixed meal, beta cell function will be evaluated from serial measurements of C-peptide. C-peptide was measured using a two-side immunometric assay using electrochemiluminescence detection.</description>
          <units>nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="537.17" spread="45.33"/>
                    <measurement group_id="O2" value="488.90" spread="45.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Month Follow Up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="561.33" spread="48.21"/>
                    <measurement group_id="O2" value="504.39" spread="35.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up</title>
        <description>Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.</description>
        <time_frame>Baseline, after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up</title>
          <description>Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.</description>
          <units>pmol/s/mg tissue</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="496.81" spread="26.54"/>
                    <measurement group_id="O2" value="564.86" spread="42.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Month Follow Up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="406.38" spread="40.39"/>
                    <measurement group_id="O2" value="495.12" spread="39.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)</title>
        <description>Sensitivity of adipose tissue lipolysis to insulin suppression, was calculated as the insulin concentration needed to suppress palmitate appearance rates (ie, flux) by 50% (IC50(palmitate)f).</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <population>The number of subjects analyzed for this outcome measure for the placebo arm was 8 instead of 9. One subject did not have blood drawn for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)</title>
          <description>Sensitivity of adipose tissue lipolysis to insulin suppression, was calculated as the insulin concentration needed to suppress palmitate appearance rates (ie, flux) by 50% (IC50(palmitate)f).</description>
          <population>The number of subjects analyzed for this outcome measure for the placebo arm was 8 instead of 9. One subject did not have blood drawn for this outcome measure.</population>
          <units>µU/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22" lower_limit="13" upper_limit="24"/>
                    <measurement group_id="O2" value="25" lower_limit="22" upper_limit="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="16" upper_limit="29"/>
                    <measurement group_id="O2" value="19" lower_limit="14" upper_limit="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Senescent Cells</title>
        <description>Tissue burden of senescent cells, which was measured by staining for senescence-associated B-galactosidase activity and expressed as the number per 100 nucleated positive cells.</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Senescent Cells</title>
          <description>Tissue burden of senescent cells, which was measured by staining for senescence-associated B-galactosidase activity and expressed as the number per 100 nucleated positive cells.</description>
          <units>number positive cells/100 total cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread="3"/>
                    <measurement group_id="O2" value="4" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread="3"/>
                    <measurement group_id="O2" value="4" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immunohistochemistry Assessments of Macrophage Burden</title>
        <description>One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess macrophage burden (total (CD68), M1 (CD14) and M2 (CD206) macrophages per 100 adipocytes).</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Immunohistochemistry Assessments of Macrophage Burden</title>
          <description>One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess macrophage burden (total (CD68), M1 (CD14) and M2 (CD206) macrophages per 100 adipocytes).</description>
          <units>macrophages per 100 adipocytes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total (CD68) baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" spread="8"/>
                    <measurement group_id="O2" value="33" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total (CD68) post intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33" spread="8"/>
                    <measurement group_id="O2" value="31" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1 (CD14) baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11" spread="6"/>
                    <measurement group_id="O2" value="13" spread="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1 (CD14) post intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14" spread="6"/>
                    <measurement group_id="O2" value="12" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M2 (CD206) baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28" spread="5"/>
                    <measurement group_id="O2" value="29" spread="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M2 (CD206) post intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29" spread="9"/>
                    <measurement group_id="O2" value="29" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Macrophage Crown-like Structures</title>
        <description>Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs). One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess the number of crown-like structures per 10 images.</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>Macrophage Crown-like Structures</title>
          <description>Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs). One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess the number of crown-like structures per 10 images.</description>
          <units>crown-like structures per 10 images</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="1"/>
                    <measurement group_id="O2" value="1" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="1"/>
                    <measurement group_id="O2" value="1" lower_limit="0" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>EPA and DHA Concentrations in Plasma</title>
        <description>Post hoc analyses were conducted to test whether EPA and DHA concentrations in plasma in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>EPA and DHA Concentrations in Plasma</title>
          <description>Post hoc analyses were conducted to test whether EPA and DHA concentrations in plasma in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.</description>
          <units>percentage of total free fatty acid</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>EPA Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.95" spread="0.22"/>
                    <measurement group_id="O2" value="1.2" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EPA Post-Intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="0.92"/>
                    <measurement group_id="O2" value="1.1" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DHA Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.89" spread="0.23"/>
                    <measurement group_id="O2" value="1.2" spread="0.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DHA Post-Intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="0.84"/>
                    <measurement group_id="O2" value="0.90" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>EPA and DHA Concentrations in Adipose Tissue</title>
        <description>Post hoc analyses were conducted to test whether EPA and DHA concentrations in subcutaneous abdominal adipose tissue in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.</description>
        <time_frame>approximately after 6 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
          </group>
        </group_list>
        <measure>
          <title>EPA and DHA Concentrations in Adipose Tissue</title>
          <description>Post hoc analyses were conducted to test whether EPA and DHA concentrations in subcutaneous abdominal adipose tissue in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.</description>
          <units>percentage of total free fatty acid</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>EPA baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.00"/>
                    <measurement group_id="O2" value="0.07" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EPA Post-Intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.19" spread="0.02"/>
                    <measurement group_id="O2" value="0.07" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DHA Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.14" spread="0.01"/>
                    <measurement group_id="O2" value="0.15" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DHA Post-Intervention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.28" spread="0.02"/>
                    <measurement group_id="O2" value="0.16" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Omega-3</title>
          <description>Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Patients in this group will be supplemented with placebo capsules containing ethyl oleate.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Ian R. Lanza</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-255-8147</phone>
      <email>lanza.ian@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01686568
org study id: 12-004590
secondary id: KL2TR000136
secondary id: U24DK100469
secondary id: DK50456
secondary id: DK40484
secondary id: 5T32DK007352
secondary id: 5UL1TR000135
nct id: NCT01686568
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to understand the effects of dietary omega-3 fats on insulin
      sensitivity in adult men and women.
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents,
      but data in humans is ambiguous. No existing studies have systematically evaluated the
      influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant,
      non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of
      purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin
      sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals.
      Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase
      the content and function of mitochondria in skeletal muscle, measured using a combination of
      in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA
      supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant
      humans, and this improvement will be associated with mitochondrial biogenesis and attenuated
      lipid accumulation in skeletal muscle and liver.

      A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo
      supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content
      of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry),
      crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining),
      as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor
      ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress
      palmitate flux by 50% (IC50(palmitate)f).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up
time frame: Baseline, after 6 months of treatment
description: A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.
measure: Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up
time frame: baseline, after 6 months of treatment
description: Following consumption of a mixed meal, beta cell function will be evaluated from serial measurements of C-peptide. C-peptide was measured using a two-side immunometric assay using electrochemiluminescence detection.
measure: Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up
time frame: Baseline, after 6 months of treatment
description: Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.
measure: Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)
time frame: approximately after 6 months of treatment
description: Sensitivity of adipose tissue lipolysis to insulin suppression, was calculated as the insulin concentration needed to suppress palmitate appearance rates (ie, flux) by 50% (IC50(palmitate)f).
measure: Senescent Cells
time frame: approximately after 6 months of treatment
description: Tissue burden of senescent cells, which was measured by staining for senescence-associated B-galactosidase activity and expressed as the number per 100 nucleated positive cells.
measure: Immunohistochemistry Assessments of Macrophage Burden
time frame: approximately after 6 months of treatment
description: One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess macrophage burden (total (CD68), M1 (CD14) and M2 (CD206) macrophages per 100 adipocytes).
measure: Macrophage Crown-like Structures
time frame: approximately after 6 months of treatment
description: Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs). One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess the number of crown-like structures per 10 images.
arm group label: Omega-3
arm group type: Experimental
description: Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
intervention type: Drug
intervention name: Omega-3
description: Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
arm group label: Omega-3
other name: Essential fatty acids
other name: Omega-3 fatty acids
other name: Omega-3 polyunsaturated fatty acids
other name: PUFAs
other name: Lovaza
intervention type: Drug
intervention name: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ian Lanza, PhD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
citation: Lalia AZ, Johnson ML, Jensen MD, Hames KC, Port JD, Lanza IR. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans. Diabetes Care. 2015 Jul;38(7):1228-37. doi: 10.2337/dc14-3101. Epub 2015 Apr 7.
PMID: 25852206
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Ian R. Lanza
investigator title: Assistant Professor of Medicine
mesh term: Insulin Resistance
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 