<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/NCT01661426</url>
  </required_header>
  <id_info>
    <org_study_id>SU-07262012-10669</org_study_id>
    <nct_id>NCT01661426</nct_id>
  </id_info>
  <brief_title>Weight Loss Diet Study: Low Carb vs Low Fat</brief_title>
  <official_title>Weight Loss Diet Study: Low Carbohydrate vs. Low Fat and Insulin Resistance Status</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hass Avocado Board</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford 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>
      The traditional weight loss diet recommended by health professionals has been a low-fat,&#xD;
      high-carbohydrate, calorie restricted diet. This recommendation has been challenged by a&#xD;
      number of alternative dietary strategies, particularly low-carbohydrate diets. In several&#xD;
      recent weight loss studies insulin resistant adults had more success with low- vs.&#xD;
      high-carbohydrate diets, in contrast to insulin sensitive adults who had either more success&#xD;
      or comparable success with the low-fat diets. The investigators enrolled 61 people with a&#xD;
      wide range of insulin sensitivity/resistance. After determining their insulin resistance&#xD;
      status, the investigators will split them in the middle and randomly assign them to one of&#xD;
      four groups for six months: (1) Low-Carbohydrate/Insulin Resistant (LC/IR); (2)&#xD;
      Low-Carbohydrate/Insulin Sensitive (LC/IS); (3) Low-Fat/Insulin Resistant (LF/IR); and (4)&#xD;
      Low-Fat/Insulin Sensitive (LF/IS) (15 people/group). After 6 months the participants will&#xD;
      switch diet for the following 6 months, i.e. those randomized to the Low-Carbohydrate diet&#xD;
      will switch to the Low-Fat diet and vice-versa. The primary outcome of this study is to&#xD;
      determine whether weight loss success can be increased if one follows the dietary approach&#xD;
      appropriately matched to their insulin resistance status. Secondary outcomes include fasting&#xD;
      insulin, glucose, lipids, and fatty acid composition.&#xD;
&#xD;
      --------------------------------------------------------------------------------&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hope to learn whether matching the weight loss diet to one's insulin&#xD;
      resistance status will increase weight loss the success. The relevance of these findings is&#xD;
      highlighted by the fact that the national recommendations for weight loss are to follow a&#xD;
      high-carbohydrate, low-fat diet. This would imply that about half the population has been&#xD;
      given the wrong advice in regards to the most successful dietary pattern for weight loss.&#xD;
&#xD;
      Plasma fatty acid composition patterns have been shown to be associated with both insulin&#xD;
      resistance and/or carbohydrate intake. As secondary analyses, the investigators will explore:&#xD;
      (1) differences in plasma fatty acid composition between insulin sensitive and resistant&#xD;
      participants at baseline; (2) the correlations between insulin markers and plasma fatty acid&#xD;
      composition at baseline; (3) the interaction between insulin status and diet on 6-month&#xD;
      changes in the plasma fatty acid composition; (4) plasma fatty acid composition changes in&#xD;
      participants on low fat and low carbohydrate diets after 6 months; and (5) the correlations&#xD;
      between changes in insulin markers, dietary components, and plasma fatty acid composition&#xD;
      after 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2012</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</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>Crossover Assignment</intervention_model>
    <intervention_model_description>The study employed a 2 x 2 crossover design: LF vs. LC diets and more IR vs. more IS. Study participants were classified as more IR or more IS based on the median AUC for insulin concentrations measured from an oral glucose tolerance test (OGTT) prior to randomization. Participants above the median were considered more IR and those below the median were considered more IS. A random number generator was used to stratify the randomization to LF vs. LC by insulin resistance status and gender. Participants followed their assigned diet for 6 months and then switched to the opposite diet for another 6 months.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in weight</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Weight change was calculated as the 12 month value minus the baseline value</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Insulin</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Fasting insulin change was calculated as the 12 month value minus the baseline value</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insulin AUC</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Insulin area under the curve (AUC) change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Glucose</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Fasting glucose change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in LDL-Cholesterol</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>LDL-cholesterol change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HDL-Cholesterol</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>HDL-cholesterol change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Triglycerides</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Triglycerides change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systolic and diastolic blood pressure</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Blood pressure change was calculated as the 12 month value minus the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma fatty acid composition at baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of the plasma fatty acid composition between insulin sensitive and resistant participants at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between insulin markers and plasma fatty acid composition at baseline.</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interaction between insulin status and diet on 6-month changes in the plasma fatty acid composition.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of plasma fatty acid composition changes in participants on low fat and low carbohydrate diets after 6 months.</measure>
    <time_frame>Baseline and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between changes in insulin markers, dietary components, and plasma fatty acid composition after 6 months.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Obesity</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Low-Carbohydrate Diet first, then Low-Fat Diet (IR)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who were more insulin resistant based on the median AUC for insulin concentrations measured from OGTT prior to randomization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-Fat Diet first, then Low-Carbohydrate Diet (IS)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who were more insulin sensitive based on the median AUC for insulin concentrations measured from OGTT prior to randomization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low-Carbohydrate Diet</intervention_name>
    <description>Counseling/instruction on how to follow a healthy low-carbohydrate diet for 6 months. One evening class/week for 8 weeks (8 total classes). Then one class every other week for 8 weeks (4 total classes). Then one class every four weeks for 8 weeks (2 total classes): 14 evening classes, total.</description>
    <arm_group_label>Low-Carbohydrate Diet first, then Low-Fat Diet (IR)</arm_group_label>
    <arm_group_label>Low-Fat Diet first, then Low-Carbohydrate Diet (IS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low-Fat Diet</intervention_name>
    <description>Counseling/instruction on how to follow a healthy low-fat diet for 6 months. One evening class/week for 8 weeks (8 total classes). Then one class every other week for 8 weeks (4 total classes). Then one class every four weeks for 8 weeks (2 total classes): 14 evening classes, total.</description>
    <arm_group_label>Low-Carbohydrate Diet first, then Low-Fat Diet (IR)</arm_group_label>
    <arm_group_label>Low-Fat Diet first, then Low-Carbohydrate Diet (IS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: &gt; or = 18 years of age&#xD;
&#xD;
          -  Women: Pre-menopausal (self-report) and &lt;50 years of age&#xD;
&#xD;
          -  Men: &lt;50 years of age&#xD;
&#xD;
          -  Race/Ethnicity: All&#xD;
&#xD;
          -  BMI (body mass index): 28-40 kg/m2 (need to lose &gt;10% body weight to achieve healthy&#xD;
             BMI)&#xD;
&#xD;
          -  Body weight stable for the last two months, and not actively on a weight loss plan&#xD;
&#xD;
          -  No plans to move from the area over the next 14 months&#xD;
&#xD;
          -  Available and able to participate in the evaluations and intervention for the study&#xD;
             period&#xD;
&#xD;
          -  Willing to accept random assignment&#xD;
&#xD;
          -  To enhance study generalizability, people on medications not noted below as specific&#xD;
             exclusions can participate if they have been stable on such medications for at least&#xD;
             three months&#xD;
&#xD;
          -  Ability and willingness to give written informed consent&#xD;
&#xD;
          -  No known active psychiatric illness&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, lactating, within 6 months post-partum, or planning to become pregnant in&#xD;
             the next 12 months; no menstruation for the previous 12 months&#xD;
&#xD;
          -  Diabetes (type 1 and 2) or history of gestational diabetes or on hypoglycemic&#xD;
             medications for any other indication&#xD;
&#xD;
          -  Prevalent diseases: Malabsorption, renal or liver disease, active neoplasms, recent&#xD;
             myocardial infarction, hypertension (except for those stable on hypertensive&#xD;
             medications) (&lt;6 months) (patient self-report and, if available, review of labs from&#xD;
             primary care provider)&#xD;
&#xD;
          -  Smokers (because of effect on weight and lipids)&#xD;
&#xD;
          -  History of serious arrhythmias, or cerebrovascular disease&#xD;
&#xD;
          -  Uncontrolled hyper- or hypothyroidism (TSH not within normal limits)&#xD;
&#xD;
          -  Medications: Lipid lowering, diabetes medications, and those known to affect&#xD;
             weight/energy expenditure&#xD;
&#xD;
          -  Excessive alcohol intake (self-reported, &gt;3 drinks/day)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher D Gardner, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://med.stanford.edu/nutrition/research/completed-studies/different-diets-and-insulin-resistance.html</url>
    <description>Study description and summary of results</description>
  </link>
  <reference>
    <citation>Gardner CD, Offringa LC, Hartle JC, Kapphahn K, Cherin R. Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity (Silver Spring). 2016 Jan;24(1):79-86. doi: 10.1002/oby.21331. Epub 2015 Dec 6.</citation>
    <PMID>26638192</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>February 18, 2023</last_update_submitted>
  <last_update_submitted_qc>February 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Christopher Gardner</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Adults</keyword>
  <keyword>Weight loss</keyword>
  <keyword>Diet</keyword>
  <keyword>Insulin Resistance</keyword>
  <keyword>Fatty acid composition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661426
org study id: SU-07262012-10669
nct id: NCT01661426
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The traditional weight loss diet recommended by health professionals has been a low-fat,
      high-carbohydrate, calorie restricted diet. This recommendation has been challenged by a
      number of alternative dietary strategies, particularly low-carbohydrate diets. In several
      recent weight loss studies insulin resistant adults had more success with low- vs.
      high-carbohydrate diets, in contrast to insulin sensitive adults who had either more success
      or comparable success with the low-fat diets. The investigators enrolled 61 people with a
      wide range of insulin sensitivity/resistance. After determining their insulin resistance
      status, the investigators will split them in the middle and randomly assign them to one of
      four groups for six months: (1) Low-Carbohydrate/Insulin Resistant (LC/IR); (2)
      Low-Carbohydrate/Insulin Sensitive (LC/IS); (3) Low-Fat/Insulin Resistant (LF/IR); and (4)
      Low-Fat/Insulin Sensitive (LF/IS) (15 people/group). After 6 months the participants will
      switch diet for the following 6 months, i.e. those randomized to the Low-Carbohydrate diet
      will switch to the Low-Fat diet and vice-versa. The primary outcome of this study is to
      determine whether weight loss success can be increased if one follows the dietary approach
      appropriately matched to their insulin resistance status. Secondary outcomes include fasting
      insulin, glucose, lipids, and fatty acid composition.

      --------------------------------------------------------------------------------
The investigators hope to learn whether matching the weight loss diet to one's insulin
      resistance status will increase weight loss the success. The relevance of these findings is
      highlighted by the fact that the national recommendations for weight loss are to follow a
      high-carbohydrate, low-fat diet. This would imply that about half the population has been
      given the wrong advice in regards to the most successful dietary pattern for weight loss.

      Plasma fatty acid composition patterns have been shown to be associated with both insulin
      resistance and/or carbohydrate intake. As secondary analyses, the investigators will explore:
      (1) differences in plasma fatty acid composition between insulin sensitive and resistant
      participants at baseline; (2) the correlations between insulin markers and plasma fatty acid
      composition at baseline; (3) the interaction between insulin status and diet on 6-month
      changes in the plasma fatty acid composition; (4) plasma fatty acid composition changes in
      participants on low fat and low carbohydrate diets after 6 months; and (5) the correlations
      between changes in insulin markers, dietary components, and plasma fatty acid composition
      after 6 months.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study employed a 2 x 2 crossover design: LF vs. LC diets and more IR vs. more IS. Study participants were classified as more IR or more IS based on the median AUC for insulin concentrations measured from an oral glucose tolerance test (OGTT) prior to randomization. Participants above the median were considered more IR and those below the median were considered more IS. A random number generator was used to stratify the randomization to LF vs. LC by insulin resistance status and gender. Participants followed their assigned diet for 6 months and then switched to the opposite diet for another 6 months.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in weight
time frame: Baseline and 12 months
description: Weight change was calculated as the 12 month value minus the baseline value
measure: Change in Fasting Insulin
time frame: Baseline and 12 months
description: Fasting insulin change was calculated as the 12 month value minus the baseline value
measure: Change in insulin AUC
time frame: Baseline and 12 months
description: Insulin area under the curve (AUC) change was calculated as the 12 month value minus the baseline value.
measure: Change in Fasting Glucose
time frame: Baseline and 12 months
description: Fasting glucose change was calculated as the 12 month value minus the baseline value.
measure: Change in LDL-Cholesterol
time frame: Baseline and 12 months
description: LDL-cholesterol change was calculated as the 12 month value minus the baseline value.
measure: Change in HDL-Cholesterol
time frame: Baseline and 12 months
description: HDL-cholesterol change was calculated as the 12 month value minus the baseline value.
measure: Change in Triglycerides
time frame: Baseline and 12 months
description: Triglycerides change was calculated as the 12 month value minus the baseline value.
measure: Change in systolic and diastolic blood pressure
time frame: Baseline and 12 months
description: Blood pressure change was calculated as the 12 month value minus the baseline value.
measure: Plasma fatty acid composition at baseline
time frame: Baseline
description: Comparison of the plasma fatty acid composition between insulin sensitive and resistant participants at baseline.
measure: Correlations between insulin markers and plasma fatty acid composition at baseline.
time frame: Baseline
measure: Interaction between insulin status and diet on 6-month changes in the plasma fatty acid composition.
time frame: 6 months
measure: Comparison of plasma fatty acid composition changes in participants on low fat and low carbohydrate diets after 6 months.
time frame: Baseline and 6 months
measure: Correlations between changes in insulin markers, dietary components, and plasma fatty acid composition after 6 months.
time frame: 6 months
arm group label: Low-Carbohydrate Diet first, then Low-Fat Diet (IR)
arm group type: Active Comparator
description: Participants who were more insulin resistant based on the median AUC for insulin concentrations measured from OGTT prior to randomization.
arm group label: Low-Fat Diet first, then Low-Carbohydrate Diet (IS)
arm group type: Active Comparator
description: Participants who were more insulin sensitive based on the median AUC for insulin concentrations measured from OGTT prior to randomization.
intervention type: Behavioral
intervention name: Low-Carbohydrate Diet
description: Counseling/instruction on how to follow a healthy low-carbohydrate diet for 6 months. One evening class/week for 8 weeks (8 total classes). Then one class every other week for 8 weeks (4 total classes). Then one class every four weeks for 8 weeks (2 total classes): 14 evening classes, total.
arm group label: Low-Carbohydrate Diet first, then Low-Fat Diet (IR)
arm group label: Low-Fat Diet first, then Low-Carbohydrate Diet (IS)
intervention type: Behavioral
intervention name: Low-Fat Diet
description: Counseling/instruction on how to follow a healthy low-fat diet for 6 months. One evening class/week for 8 weeks (8 total classes). Then one class every other week for 8 weeks (4 total classes). Then one class every four weeks for 8 weeks (2 total classes): 14 evening classes, total.
arm group label: Low-Carbohydrate Diet first, then Low-Fat Diet (IR)
arm group label: Low-Fat Diet first, then Low-Carbohydrate Diet (IS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher D Gardner, PhD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
url: https://med.stanford.edu/nutrition/research/completed-studies/different-diets-and-insulin-resistance.html
description: Study description and summary of results
citation: Gardner CD, Offringa LC, Hartle JC, Kapphahn K, Cherin R. Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity (Silver Spring). 2016 Jan;24(1):79-86. doi: 10.1002/oby.21331. Epub 2015 Dec 6.
PMID: 26638192
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Christopher Gardner
investigator title: Associate Professor of Medicine
mesh term: Insulin Resistance
mesh term: Weight Loss
sharing ipd: No