<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/NCT02199483</url>
  </required_header>
  <id_info>
    <org_study_id>140154</org_study_id>
    <secondary_id>14-DK-0154</secondary_id>
    <nct_id>NCT02199483</nct_id>
  </id_info>
  <brief_title>Metabolic and Neural Adaptations to Weight Loss, Plateau, and Regain</brief_title>
  <official_title>Metabolic and Neural Adaptations to Weight Loss, Plateau, and Regain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Many people can lose weight by changing their diet or exercise. However, most people&#xD;
      eventually regain the weight over time. This weight regain may be related to changes in&#xD;
      metabolism as well as changes in the brain caused by weight loss. Researchers want to learn&#xD;
      more about these changes.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To see how weight loss and regain affects the body s metabolism and the brain of obese but&#xD;
      healthy adults.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Obese but healthy adults age 18-55 who plan to participate in a weight loss program at one&#xD;
      of several participating clinics or resorts.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will first be screened at home through questionnaires and telephone&#xD;
           interviews.&#xD;
&#xD;
        -  Participants will then be screened at the NIH with blood tests, medical history,&#xD;
           physical exam, electrocardiograms, and questionnaires. They will have a mock magnetic&#xD;
           resonance imaging (MRI) scan.&#xD;
&#xD;
        -  At visit 1, participants will stay at the NIH and will:&#xD;
&#xD;
        -  have MRI and PET brain scans.&#xD;
&#xD;
        -  have body composition scans and measurements.&#xD;
&#xD;
        -  give blood samples.&#xD;
&#xD;
        -  eat a special diet.&#xD;
&#xD;
        -  wear a physical activity monitor.&#xD;
&#xD;
        -  provide a urine sample and body weight daily.&#xD;
&#xD;
        -  drink a special type of water to measure calorie burn.&#xD;
&#xD;
        -  wear a clear plastic hood over their head while lying down, to collect exhaled air.&#xD;
&#xD;
        -  spend 24 hours in a room that measures oxygen and carbon dioxide.&#xD;
&#xD;
        -  complete questionnaires and computer tasks.&#xD;
&#xD;
        -  After visit 1, participants will give daily urine samples and weight and physical&#xD;
           activity measurements from home. Then they will follow a lifestyle intervention for&#xD;
           weight loss and give daily weight and activity measurements.&#xD;
&#xD;
        -  Visits 2, 3, and 4 occur 1-26 months after the start of the weight loss program.&#xD;
           Participants will repeat procedures from visit 1. Visits 1-4 last 4 days each.&#xD;
&#xD;
        -  Researchers will track participants weight and physical activity for up to 26 months&#xD;
           after visit 2.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lifestyle interventions can result in weight loss, but most people experience a plateau after&#xD;
      6-10 months when weight stabilizes and many subsequently regain weight over the subsequent&#xD;
      months. This pattern of weight plateau and regain is typical and appears to be independent of&#xD;
      the lifestyle intervention used. The apparent resistance to further weight loss in not well&#xD;
      understood.&#xD;
&#xD;
      We recently demonstrated that participants engaged in an intensive intervention employing&#xD;
      caloric restriction and vigorous exercise had a profound slowing of metabolism that was&#xD;
      significantly greater than expected due to weight loss alone. This phenomenon is called&#xD;
      metabolic adaptation and has also been observed following weight loss through caloric&#xD;
      restriction without exercise and may persist long after weight loss has ceased. Metabolic&#xD;
      adaptation has been hypothesized to limit weight loss and predispose individuals to weight&#xD;
      regain, but this has yet to be demonstrated and the concept is controversial. In addition to&#xD;
      the metabolic adaptations to weight loss, the brain also adapts in ways that enhance the&#xD;
      activation of reward regions in response to palatable food cues and their receipt. In&#xD;
      particular, the brain s dopamine circuitry is believed to be altered in obesity and it is&#xD;
      presently unclear how this pathway responds to a weight loss intervention in humans.&#xD;
&#xD;
      The primary aims of this study are to investigate the metabolic and neural adaptations in 60&#xD;
      obese adult volunteers participating in lifestyle interventions resulting in weight loss&#xD;
      through a structured meal replacement program or caloric restriction plus vigorous exercise.&#xD;
      The secondary aim is to determine whether the magnitude of metabolic adaptation or the&#xD;
      changes in the brain s reward circuitry or responsiveness to food cues are related to the&#xD;
      ubiquitous weight loss plateau after 6-10 months or the rate of weight regain in the&#xD;
      subsequent months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>July 21, 2014</start_date>
  <completion_date type="Actual">June 29, 2017</completion_date>
  <primary_completion_date type="Actual">June 29, 2017</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>To measure metabolic and neural adaptations after 4-12 weeks, 6-10 months, and 22-26 months following the start of a lifestyle intervention resulting in weight loss.</measure>
    <time_frame>ongoing</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine whether the degree of metabolic or neural adaptation at 4-12 weeks is correlated with the weight plateau at 6-10 months or the rate of weight regain in the subsequent months.</measure>
    <time_frame>ongoing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To investigate changes in circulating hormone and metabolites that correlate with metabolic and neural adaptations as well as changes in appetitive behaviors following a lifestyle intervention resulting in weight loss.</measure>
    <time_frame>ongoing</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">0</enrollment>
  <condition>Healthy Volunteers</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Age 18-55 years, male and female&#xD;
&#xD;
          -  Recent weight stability (&lt; plus and minus 2 % over past 1 month)&#xD;
&#xD;
          -  Body mass index (BMI) greater than or equal to 30 kg/m2&#xD;
&#xD;
          -  Able to complete daily bouts of moderate to vigorous exercise (when applicable)&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Have reserved a stay of at least 4 weeks at The Biggest Loser Resort or have enrolled&#xD;
             in a structured meal replacement weight loss program at the Washington Center for&#xD;
             Weight Management and Research, the National Center for Weight and Wellness, or the&#xD;
             Johns Hopkins Weight Management Center.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Body weight &gt; 400 lbs (weight limit of PET and MRI scanners)&#xD;
&#xD;
          -  BMI &lt; 30 kg/m2&#xD;
&#xD;
          -  Less than 80% of maximum lifetime weight&#xD;
&#xD;
          -  Hypertension if&#xD;
&#xD;
               -  (1) &gt;160/100;&#xD;
&#xD;
               -  (2) 140/90 to 159/99 with evidence of target organ damage (e.g. elevated serum&#xD;
                  creatinine, proteinuria, abnormal EKG, retinopathy);&#xD;
&#xD;
               -  (3) &gt;140/90 on antihypertensive medications.&#xD;
&#xD;
          -  Evidence of metabolic or cardiovascular disease, or disease that may influence&#xD;
             metabolism (e.g. cancer, thyroid disease)&#xD;
&#xD;
          -  Past or present history of eating disorder (including binge eating) or psychiatric&#xD;
             disease&#xD;
&#xD;
          -  Taking any prescription medication or other drug that may influence metabolism (e.g.&#xD;
             diet/weight-loss medication, asthma medication, psychiatric medications,&#xD;
             corticosteroids, or other medications at the discretion of the PI and/or study team)&#xD;
&#xD;
          -  Hematocrit &lt; 34% (women only)&#xD;
&#xD;
          -  Hematocrit &lt; 40% (men only)&#xD;
&#xD;
          -  Pregnancy, lactation (women only)&#xD;
&#xD;
          -  Women who become pregnant during the two-year study period&#xD;
&#xD;
          -  Recent participation in a regular exercise program (&gt; 4h/week of vigorous activity)&#xD;
&#xD;
          -  Previous bariatric surgery&#xD;
&#xD;
          -  Caffeine consumption &gt; 500 mg/day&#xD;
&#xD;
          -  Regular use of alcohol (&gt;2 drinks per day), tobacco (smoking or chewing) amphetamines,&#xD;
             cocaine, heroin, or marijuana over past 6 months&#xD;
&#xD;
          -  Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food&#xD;
             allergies)&#xD;
&#xD;
          -  Having metal implants incompatible with MRI (for example, pacemakers, metallic&#xD;
             prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).&#xD;
&#xD;
          -  Non-native English speakers&#xD;
&#xD;
          -  Volunteers unwilling or unable to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Hall, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Franz MJ, VanWormer JJ, Crain AL, Boucher JL, Histon T, Caplan W, Bowman JD, Pronk NP. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc. 2007 Oct;107(10):1755-67. doi: 10.1016/j.jada.2007.07.017.</citation>
    <PMID>17904936</PMID>
  </reference>
  <reference>
    <citation>Arone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. Autonomic nervous system activity in weight gain and weight loss. Am J Physiol. 1995 Jul;269(1 Pt 2):R222-5. doi: 10.1152/ajpregu.1995.269.1.R222.</citation>
    <PMID>7631897</PMID>
  </reference>
  <reference>
    <citation>Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E, Hall KD. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012 Jul;97(7):2489-96. doi: 10.1210/jc.2012-1444. Epub 2012 Apr 24. Erratum In: J Clin Endocrinol Metab. 2016 May;101(5):2266.</citation>
    <PMID>22535969</PMID>
  </reference>
  <verification_date>June 29, 2017</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>December 11, 2019</last_update_submitted>
  <last_update_submitted_qc>December 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Energy Expenditure</keyword>
  <keyword>Behavioral Weight Loss Treatment</keyword>
  <keyword>Neurocognitive Function</keyword>
  <keyword>Weight Loss</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <!-- 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/NCT02199483
org study id: 140154
secondary id: 14-DK-0154
nct id: NCT02199483
lead sponsor: 
Background:

      - Many people can lose weight by changing their diet or exercise. However, most people
      eventually regain the weight over time. This weight regain may be related to changes in
      metabolism as well as changes in the brain caused by weight loss. Researchers want to learn
      more about these changes.

      Objective:

      - To see how weight loss and regain affects the body s metabolism and the brain of obese but
      healthy adults.

      Eligibility:

      - Obese but healthy adults age 18-55 who plan to participate in a weight loss program at one
      of several participating clinics or resorts.

      Design:

        -  Participants will first be screened at home through questionnaires and telephone
           interviews.

        -  Participants will then be screened at the NIH with blood tests, medical history,
           physical exam, electrocardiograms, and questionnaires. They will have a mock magnetic
           resonance imaging (MRI) scan.

        -  At visit 1, participants will stay at the NIH and will:

        -  have MRI and PET brain scans.

        -  have body composition scans and measurements.

        -  give blood samples.

        -  eat a special diet.

        -  wear a physical activity monitor.

        -  provide a urine sample and body weight daily.

        -  drink a special type of water to measure calorie burn.

        -  wear a clear plastic hood over their head while lying down, to collect exhaled air.

        -  spend 24 hours in a room that measures oxygen and carbon dioxide.

        -  complete questionnaires and computer tasks.

        -  After visit 1, participants will give daily urine samples and weight and physical
           activity measurements from home. Then they will follow a lifestyle intervention for
           weight loss and give daily weight and activity measurements.

        -  Visits 2, 3, and 4 occur 1-26 months after the start of the weight loss program.
           Participants will repeat procedures from visit 1. Visits 1-4 last 4 days each.

        -  Researchers will track participants weight and physical activity for up to 26 months
           after visit 2.
Lifestyle interventions can result in weight loss, but most people experience a plateau after
      6-10 months when weight stabilizes and many subsequently regain weight over the subsequent
      months. This pattern of weight plateau and regain is typical and appears to be independent of
      the lifestyle intervention used. The apparent resistance to further weight loss in not well
      understood.

      We recently demonstrated that participants engaged in an intensive intervention employing
      caloric restriction and vigorous exercise had a profound slowing of metabolism that was
      significantly greater than expected due to weight loss alone. This phenomenon is called
      metabolic adaptation and has also been observed following weight loss through caloric
      restriction without exercise and may persist long after weight loss has ceased. Metabolic
      adaptation has been hypothesized to limit weight loss and predispose individuals to weight
      regain, but this has yet to be demonstrated and the concept is controversial. In addition to
      the metabolic adaptations to weight loss, the brain also adapts in ways that enhance the
      activation of reward regions in response to palatable food cues and their receipt. In
      particular, the brain s dopamine circuitry is believed to be altered in obesity and it is
      presently unclear how this pathway responds to a weight loss intervention in humans.

      The primary aims of this study are to investigate the metabolic and neural adaptations in 60
      obese adult volunteers participating in lifestyle interventions resulting in weight loss
      through a structured meal replacement program or caloric restriction plus vigorous exercise.
      The secondary aim is to determine whether the magnitude of metabolic adaptation or the
      changes in the brain s reward circuitry or responsiveness to food cues are related to the
      ubiquitous weight loss plateau after 6-10 months or the rate of weight regain in the
      subsequent months.
observational model: Cohort
time perspective: Prospective
measure: To measure metabolic and neural adaptations after 4-12 weeks, 6-10 months, and 22-26 months following the start of a lifestyle intervention resulting in weight loss.
time frame: ongoing
measure: To determine whether the degree of metabolic or neural adaptation at 4-12 weeks is correlated with the weight plateau at 6-10 months or the rate of weight regain in the subsequent months.
time frame: ongoing
measure: To investigate changes in circulating hormone and metabolites that correlate with metabolic and neural adaptations as well as changes in appetitive behaviors following a lifestyle intervention resulting in weight loss.
time frame: ongoing
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kevin Hall, Ph.D.
role: Principal Investigator
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
country: United States
citation: Franz MJ, VanWormer JJ, Crain AL, Boucher JL, Histon T, Caplan W, Bowman JD, Pronk NP. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc. 2007 Oct;107(10):1755-67. doi: 10.1016/j.jada.2007.07.017.
PMID: 17904936
citation: Arone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. Autonomic nervous system activity in weight gain and weight loss. Am J Physiol. 1995 Jul;269(1 Pt 2):R222-5. doi: 10.1152/ajpregu.1995.269.1.R222.
PMID: 7631897
citation: Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E, Hall KD. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012 Jul;97(7):2489-96. doi: 10.1210/jc.2012-1444. Epub 2012 Apr 24. Erratum In: J Clin Endocrinol Metab. 2016 May;101(5):2266.
PMID: 22535969
responsible party type: Sponsor
mesh term: Weight Loss