<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/NCT03779048</url>
  </required_header>
  <id_info>
    <org_study_id>832077</org_study_id>
    <nct_id>NCT03779048</nct_id>
  </id_info>
  <brief_title>Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment</brief_title>
  <official_title>Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a two-phase study. Phase 1 will evaluate obesity-related behavioral and biological&#xD;
      characteristics as potential predictors of response to behavioral treatment (BT) for weight&#xD;
      loss. Phase 2 is a double-blind, placebo-controlled, RCT to test whether adding weight loss&#xD;
      medication to BT improves 24-week weight loss, as compared to BT with placebo, in subjects&#xD;
      identified as having suboptimal early weight loss after 4 weeks of individual behavioral&#xD;
      weight control. All participants, regardless of their early weight loss, will receive the&#xD;
      same BT program of diet, physical activity, and behavior therapy for weight loss for an&#xD;
      additional 24 weeks (28 total weeks of treatment).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will be a total of 150 adults, aged 21-70 years, with a body mass index (BMI) of 31&#xD;
      kg/m2 or above (28 kg/m2 with an obesity-related comorbidity). In phase 1, eligible subjects&#xD;
      will complete questionnaires and an in-person baseline assessment of obesity-related&#xD;
      behavioral characteristics (satiety, hunger, the relative reinforcing value of food&#xD;
      [RRVfood], and impulsivity [delay discounting]), neuropeptides, and gastric emptying. After&#xD;
      this baseline assessment, participants will begin an initial 4-week behavioral treatment (BT)&#xD;
      &quot;run-in&quot; delivered individually in 20-30 minute weekly sessions (delivered virtually).&#xD;
&#xD;
      The primary goal of phase 1 will be to evaluate baseline satiety, postprandial change in&#xD;
      GLP-1, and gastric emptying as predictors of percent weight loss after 4 weeks of BT. We will&#xD;
      also examine whether these variables predict categorization as a suboptimal early responder&#xD;
      to BT (e.g., &lt;2.0% loss; co-primary outcome).&#xD;
&#xD;
      Secondary endpoints of phase 1 are percent weight loss from the start of the BT run-in (week&#xD;
      -4) to randomization (week 0) and categorization as a suboptimal early responder, as&#xD;
      predicted by additional behavioral characteristics (hunger as measured by VAS ratings,&#xD;
      RRVfood as measured using a computer task, and impulsivity as measured using a delay&#xD;
      discounting computer task) and neuropeptides (higher fasting ghrelin, lower fasting leptin,&#xD;
      and lower postprandial changes in insulin and PYY).&#xD;
&#xD;
      In phase 2, suboptimal early responders (based on weight loss during the BT run-in) will be&#xD;
      randomly assigned to 24 weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M;&#xD;
      phentermine 15.0 mg). Both treatment groups will continue to attend 20-30 minute individual&#xD;
      BT sessions (delivered virtually), weekly for the first 12 weeks and every other week for the&#xD;
      last 12 weeks (total of 18 visits). Both treatment groups will also take once daily study&#xD;
      medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.&#xD;
      Early BT responders identified during the run-in will receive the same 24-week BT program,&#xD;
      but will not receive study medication or be included in the randomized trial.&#xD;
&#xD;
      The assessments administered at baseline - questionnaires, including behavioral testing,&#xD;
      blood draws, and measurements of body weight - will be repeated at randomization (week 0) and&#xD;
      at week 24.&#xD;
&#xD;
      The primary endpoint of phase 2 is change in body weight (i.e., % reduction in initial&#xD;
      weight), as measured from randomization to week 24, among suboptimal early responders&#xD;
      assigned to BT+P vs. BT+M. A randomized sample size of 50 non-responders (25 per group),&#xD;
      assuming a 20% attrition rate, will give us 81.5% power to detect between-treatment group&#xD;
      differences at week 24 of 4.5% (effect size: d = 0.82).&#xD;
&#xD;
      Secondary endpoints of phase 2 will include change in body weight in kg from randomization to&#xD;
      week 24, as well as the portion of suboptimal early responders who achieve a&#xD;
      post-randomization loss of ≥ 5% and ≥ 10% of initial body weight. We will also examine&#xD;
      differences between suboptimal early responders treated with BT+M vs. BT+P in changes in&#xD;
      hunger, satiety, the reinforcing efficacy of food, and impulsivity between randomization and&#xD;
      week 24. A comparison will also be made in percent weight loss from randomization to week 24&#xD;
      between suboptimal early responders treated with BT+M and early responders treated with BT&#xD;
      alone.&#xD;
&#xD;
      If you are interested in participating in this study, information and a link to contact the&#xD;
      research team can be found here: https://clinicalresearch.itmat.upenn.edu/3XOX/ or you can&#xD;
      call us at the numbers listed below.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Actual">May 25, 2022</completion_date>
  <primary_completion_date type="Actual">May 25, 2022</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Percent weight loss</measure>
    <time_frame>Week -4 (start of BT run-in) to week 0 (randomization)</time_frame>
    <description>Co-primary outcomes - phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of participants who are categorized as early non-responders at randomization, based on percent weight loss</measure>
    <time_frame>Week -4 (start of BT run-in) to week 0 (randomization)</time_frame>
    <description>Co-primary outcomes - phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Baseline satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.</measure>
    <time_frame>Baseline (week -5)</time_frame>
    <description>Primary predictor variable - phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Baseline postprandial change in GLP-1 during a test meal</measure>
    <time_frame>Baseline</time_frame>
    <description>Primary predictor variable - phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Baseline gastric emptying during a test meal (acetaminophen test)</measure>
    <time_frame>Baseline</time_frame>
    <description>Primary predictor variable - phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Percent weight loss</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Primary outcomes - phase 2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline hunger, as measured by visual analogue scales (range 0-100 mm, higher = more hunger) during a test meal</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline relative reinforcing value of food (computer task), number of food reinforcer points earned</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline delay discounting (computer task), area under the curve representing the ratio of immediate reward size to time delay</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline implicit wanting of food, reaction time on Leeds Food Preference Questionnaire</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline fasting ghrelin</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline fasting leptin</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline postprandial change in insulin during a test meal</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Baseline postprandial change in peptide YY during a test meal</measure>
    <time_frame>Baseline</time_frame>
    <description>Secondary predictor variable - phase 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Weight loss (kg)</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of participants with a weight loss of 5% or greater of randomization body weight at week 24</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of participants with a weight loss of 10% or greater of randomization body weight at week 24</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change in satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change in hunger, as measured by visual analogue scales (range 0-100 mm, higher=more hunger) during a test meal</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change in relative reinforcing value of food (computer task), number of food reinforcer points earned</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change in delay discounting (computer task), area under the curve representing the ratio of immediate reward size to time delay</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Secondary outcomes - phase 2</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline eating behavior as measured by The Eating Inventory (EI); Dietary restraint subscale (scored 0-21 higher=more restraint), Disinhibition sub scale (scored 0-16 higher=more disinhibition), Hunger sub scale (scored 0-14 higher=more hunger)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm, higher=greater amount or frequency)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline reinforcing value of food as measured by the Power of Food Scale (PFS; range 1-5, higher=greater power of food)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline sensitivity to reward as measured by the Behavioral Inhibition/Activation Scale (BIS/BAS) (BIS subscale range 7-28, higher = greater inhibition; BAS reward responsiveness sub scale range 5-20, higher=greater reward responsiveness, etc)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline impulsivity as measured by The Barratt Impulsiveness Scale (BIS-15, range 15-60, higher= more impulsiveness)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline binge eating as measured by The Questionnaire on Eating and Weight Patterns (QEWP-5); Measure categorizes participants based on whether they may meet diagnostic criteria for binge eating disorder</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline craving frequency as measured by the Food Craving Q Trait - Reduced</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline emotional eating as measured by the Dutch Eating Behaviour Questionnaire (DEBQ)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline perceived barriers to healthy eating and physical activity (Scale by Welsh et al., 2012)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline Weight Efficacy Life-Style Questionnaire (WEL)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline SCI Exercise Self Efficacy Scale (ESES)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Randomization Ball and Crawford Social Support Scale</measure>
    <time_frame>Randomization (week 0)</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline food addiction using the Yale Food Addiction Scale (YFAS)</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: The reinforcing efficacy of high- and low-calorie food</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline sleep hours survey</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline Perceived Stress Scale</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline anxiety as measured by the GAD-7</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 1: Baseline general mindfulness and acceptance as measured using the Philadelphia Mindfulness Scale</measure>
    <time_frame>Baseline</time_frame>
    <description>Exploratory predictor variable - phase 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in blood pressure</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in pulse</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in waist circumference</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in triglycerides</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in HDL and LDL cholesterol</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in fasting blood sugar</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm)</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in quality of life as measured by the Impact of Weight on Quality of Life (IWQOL)</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2: Change in physical activity using the Paffenbarger Physical Activity Questionnaire</measure>
    <time_frame>Week 0 (randomization) to week 24</time_frame>
    <description>Exploratory outcomes - phase 2</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">147</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Behavioral Treatment + Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All participants will complete an initial 4-week behavioral treatment (BT) run-in. Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.&#xD;
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Behavioral Treatment + Medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All participants will complete an initial 4-week behavioral treatment (BT) run-in. Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.&#xD;
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Behavioral Treatment</intervention_name>
    <description>Behavioral treatment (BT) for weight loss includes diet and physical activity recommendations and behavior therapy strategies. All participants will complete an initial 4-week BT run-in, delivered in individual, 20-30 minute weekly sessions. After the end of the run-in, participants will be offered an additional 24 weeks of 20-30 minute individual BT sessions, occurring weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits).</description>
    <arm_group_label>Behavioral Treatment + Medication</arm_group_label>
    <arm_group_label>Behavioral Treatment + Placebo</arm_group_label>
    <other_name>Lifestyle modification</other_name>
    <other_name>Behavioral weight loss</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.</description>
    <arm_group_label>Behavioral Treatment + Placebo</arm_group_label>
    <other_name>Placebo for medication</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phentermine 15 MG</intervention_name>
    <description>The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.</description>
    <arm_group_label>Behavioral Treatment + Medication</arm_group_label>
    <other_name>Medication</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. BMI ≥ 31 kg/m² (or 28 kg/m2 with obesity-related comorbidity)&#xD;
&#xD;
          2. Age ≥ 21 years and ≤ 70 years&#xD;
&#xD;
          3. Eligible female patients will be:&#xD;
&#xD;
               -  non-pregnant, evidenced by a negative urine pregnancy test&#xD;
&#xD;
               -  non-lactating&#xD;
&#xD;
               -  surgically sterile or postmenopausal, or they will agree to continue to use an&#xD;
                  accepted method of birth control during the study. Acceptable methods of birth&#xD;
                  control are: hormonal contraceptives; double barrier method (condom with&#xD;
                  spermicide or diaphragm with spermicide); intrauterine device; surgical&#xD;
                  sterility; abstinence; and/or postmenopausal status (defined as at least 2 years&#xD;
                  without menses).&#xD;
&#xD;
          4. Subjects must:&#xD;
&#xD;
               -  have a primary care provider (PCP) who is responsible for providing routine care&#xD;
&#xD;
               -  understand and be willing to comply with all study-related procedures and agree&#xD;
                  to participate in the study by giving written informed consent&#xD;
&#xD;
               -  plan to remain in the Philadelphia area for the next 9 months or more&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or nursing, or plans to become pregnant in the next 9 months.&#xD;
&#xD;
          2. Uncontrolled hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood&#xD;
             pressure ≥ 90 mm Hg)&#xD;
&#xD;
          3. Type 1 diabetes&#xD;
&#xD;
          4. Type 2 diabetes&#xD;
&#xD;
          5. A fasting blood glucose &gt; 126 mg/dL (on second assessment after first elevated value)&#xD;
&#xD;
          6. History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias,&#xD;
             congestive heart failure, or heart block greater than first degree&#xD;
&#xD;
          7. Clinically significant hepatic or renal disease&#xD;
&#xD;
          8. Hyperthyroidism&#xD;
&#xD;
          9. Other thyroid disease, not controlled&#xD;
&#xD;
         10. History of malignancy (except for non-melanoma skin cancer) in past 5 years&#xD;
&#xD;
         11. Narrow angle glaucoma&#xD;
&#xD;
         12. Presence or history of marked agitation&#xD;
&#xD;
         13. Current severe major depressive episode (BDI-II score ≥ 29), current active suicidal&#xD;
             ideation, or history of suicide attempts within the past 5 years.&#xD;
&#xD;
         14. Any severity of thought or bipolar disorder, or bulimia nervosa.&#xD;
&#xD;
         15. Psychiatric hospitalization within the past 6 months&#xD;
&#xD;
         16. Self-reported alcohol or substance abuse within the past 6 months, including at-risk&#xD;
             drinking (current consumption of ≥ 14 alcoholic drinks per week)&#xD;
&#xD;
         17. Past year history of drug abuse&#xD;
&#xD;
         18. Use in the past 2 weeks of monoamine oxidase inhibitors&#xD;
&#xD;
         19. Current use of serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g. venlafaxine,&#xD;
             duloxetine, desvenlafaxine, milnacipran, levomilnacipran).&#xD;
&#xD;
         20. Use in past 6 months of medications known to induce significant weight loss (i.e.,&#xD;
             prescription weight loss medications) or weight gain (e.g., chronic use of oral&#xD;
             steroids, second generation antipsychotics)&#xD;
&#xD;
         21. Loss of ≥ 5% of initial body weight within the past 6 months&#xD;
&#xD;
         22. History of (or plans for) bariatric surgery (e.g., roux en y gastric bypass, sleeve&#xD;
             gastrectomy, gastric banding), endoscopic intragastric balloon, or aspire assist.&#xD;
&#xD;
         23. Inability to walk 5 blocks comfortably or engage in some other form of aerobic&#xD;
             activity (e.g., swimming)&#xD;
&#xD;
         24. Known or suspected allergy to sympathomimetic amines or related products&#xD;
&#xD;
         25. The receipt of any investigational drug within 6 months prior to this trial&#xD;
&#xD;
         26. Previous participation in this trial (e.g., randomized and failed to participate)&#xD;
&#xD;
         27. Changes to any chronic medication (type or dosage) within the past 3 months.&#xD;
&#xD;
         28. Any serious or unstable medical or psychological condition that, in the opinion of the&#xD;
             investigator, would compromise the patient's safety or successful participation in the&#xD;
             study&#xD;
&#xD;
        Other Therapy: Subjects will be expected to use medications (prescribed by their PCP) to&#xD;
        control traditional cardiometabolic risk factors (e.g., hypertension, hypercholesterolemia,&#xD;
        etc) and other co-morbid conditions, with the exception of medications listed above under&#xD;
        &quot;exclusions.&quot; In all cases, the subjects' PCP will be asked at the study's outset to keep&#xD;
        medication does constant throughout the study, whenever possible. Subjects will be expected&#xD;
        to have been on their medication regimen (including the dose) for 3 months prior to&#xD;
        beginning the BT program.&#xD;
&#xD;
        To be eligible to participate in the randomized phase of the trial, subjects must also:&#xD;
&#xD;
          1. Complete at least 3 out of 4 treatment sessions during the 4-week BT run-in and attend&#xD;
             a randomization visit. Attending an in-person makeup session within one week of a&#xD;
             missed visit will count as having attended the run-in visit.&#xD;
&#xD;
          2. Lose &lt; 2.0% of initial weight during the 4-week BT run-in.&#xD;
&#xD;
        Early BT responders who lose&gt;=2% during the BT run-in will be offered the same 24-week BT&#xD;
        program, but will not receive study medication or be included in the randomized trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jena S Tronieri, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Perelman School of Medicine at the University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania Center for Weight and Eating Disorders</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>phentermine</keyword>
  <keyword>Hypoglycemic agents</keyword>
  <keyword>Incretins</keyword>
  <keyword>Hormones</keyword>
  <keyword>Appetitive Behavior</keyword>
  <keyword>Appetite Depressants</keyword>
  <keyword>Anti-Obesity Agents</keyword>
  <keyword>Weight Loss</keyword>
  <keyword>Body Weight</keyword>
  <keyword>Body Weight Changes</keyword>
  <keyword>Signs and Symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phentermine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 9, 2023</submitted>
    <returned>June 6, 2023</returned>
    <submitted>August 29, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03779048
org study id: 832077
nct id: NCT03779048
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a two-phase study. Phase 1 will evaluate obesity-related behavioral and biological
      characteristics as potential predictors of response to behavioral treatment (BT) for weight
      loss. Phase 2 is a double-blind, placebo-controlled, RCT to test whether adding weight loss
      medication to BT improves 24-week weight loss, as compared to BT with placebo, in subjects
      identified as having suboptimal early weight loss after 4 weeks of individual behavioral
      weight control. All participants, regardless of their early weight loss, will receive the
      same BT program of diet, physical activity, and behavior therapy for weight loss for an
      additional 24 weeks (28 total weeks of treatment).
Subjects will be a total of 150 adults, aged 21-70 years, with a body mass index (BMI) of 31
      kg/m2 or above (28 kg/m2 with an obesity-related comorbidity). In phase 1, eligible subjects
      will complete questionnaires and an in-person baseline assessment of obesity-related
      behavioral characteristics (satiety, hunger, the relative reinforcing value of food
      [RRVfood], and impulsivity [delay discounting]), neuropeptides, and gastric emptying. After
      this baseline assessment, participants will begin an initial 4-week behavioral treatment (BT)
      "run-in" delivered individually in 20-30 minute weekly sessions (delivered virtually).

      The primary goal of phase 1 will be to evaluate baseline satiety, postprandial change in
      GLP-1, and gastric emptying as predictors of percent weight loss after 4 weeks of BT. We will
      also examine whether these variables predict categorization as a suboptimal early responder
      to BT (e.g., <2.0% loss; co-primary outcome).

      Secondary endpoints of phase 1 are percent weight loss from the start of the BT run-in (week
      -4) to randomization (week 0) and categorization as a suboptimal early responder, as
      predicted by additional behavioral characteristics (hunger as measured by VAS ratings,
      RRVfood as measured using a computer task, and impulsivity as measured using a delay
      discounting computer task) and neuropeptides (higher fasting ghrelin, lower fasting leptin,
      and lower postprandial changes in insulin and PYY).

      In phase 2, suboptimal early responders (based on weight loss during the BT run-in) will be
      randomly assigned to 24 weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M;
      phentermine 15.0 mg). Both treatment groups will continue to attend 20-30 minute individual
      BT sessions (delivered virtually), weekly for the first 12 weeks and every other week for the
      last 12 weeks (total of 18 visits). Both treatment groups will also take once daily study
      medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
      Early BT responders identified during the run-in will receive the same 24-week BT program,
      but will not receive study medication or be included in the randomized trial.

      The assessments administered at baseline - questionnaires, including behavioral testing,
      blood draws, and measurements of body weight - will be repeated at randomization (week 0) and
      at week 24.

      The primary endpoint of phase 2 is change in body weight (i.e., % reduction in initial
      weight), as measured from randomization to week 24, among suboptimal early responders
      assigned to BT+P vs. BT+M. A randomized sample size of 50 non-responders (25 per group),
      assuming a 20% attrition rate, will give us 81.5% power to detect between-treatment group
      differences at week 24 of 4.5% (effect size: d = 0.82).

      Secondary endpoints of phase 2 will include change in body weight in kg from randomization to
      week 24, as well as the portion of suboptimal early responders who achieve a
      post-randomization loss of ≥ 5% and ≥ 10% of initial body weight. We will also examine
      differences between suboptimal early responders treated with BT+M vs. BT+P in changes in
      hunger, satiety, the reinforcing efficacy of food, and impulsivity between randomization and
      week 24. A comparison will also be made in percent weight loss from randomization to week 24
      between suboptimal early responders treated with BT+M and early responders treated with BT
      alone.

      If you are interested in participating in this study, information and a link to contact the
      research team can be found here: https://clinicalresearch.itmat.upenn.edu/3XOX/ or you can
      call us at the numbers listed below.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind
measure: Phase 1: Percent weight loss
time frame: Week -4 (start of BT run-in) to week 0 (randomization)
description: Co-primary outcomes - phase 1
measure: Phase 1: Number of participants who are categorized as early non-responders at randomization, based on percent weight loss
time frame: Week -4 (start of BT run-in) to week 0 (randomization)
description: Co-primary outcomes - phase 1
measure: Phase 1: Baseline satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.
time frame: Baseline (week -5)
description: Primary predictor variable - phase 1
measure: Phase 1: Baseline postprandial change in GLP-1 during a test meal
time frame: Baseline
description: Primary predictor variable - phase 1
measure: Phase 1: Baseline gastric emptying during a test meal (acetaminophen test)
time frame: Baseline
description: Primary predictor variable - phase 1
measure: Phase 2: Percent weight loss
time frame: Week 0 (randomization) to week 24
description: Primary outcomes - phase 2
measure: Phase 1: Baseline hunger, as measured by visual analogue scales (range 0-100 mm, higher = more hunger) during a test meal
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline relative reinforcing value of food (computer task), number of food reinforcer points earned
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline delay discounting (computer task), area under the curve representing the ratio of immediate reward size to time delay
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline implicit wanting of food, reaction time on Leeds Food Preference Questionnaire
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline fasting ghrelin
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline fasting leptin
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline postprandial change in insulin during a test meal
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 1: Baseline postprandial change in peptide YY during a test meal
time frame: Baseline
description: Secondary predictor variable - phase 1
measure: Phase 2: Weight loss (kg)
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Number of participants with a weight loss of 5% or greater of randomization body weight at week 24
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Number of participants with a weight loss of 10% or greater of randomization body weight at week 24
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Change in satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Change in hunger, as measured by visual analogue scales (range 0-100 mm, higher=more hunger) during a test meal
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Change in relative reinforcing value of food (computer task), number of food reinforcer points earned
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 2: Change in delay discounting (computer task), area under the curve representing the ratio of immediate reward size to time delay
time frame: Week 0 (randomization) to week 24
description: Secondary outcomes - phase 2
measure: Phase 1: Baseline eating behavior as measured by The Eating Inventory (EI); Dietary restraint subscale (scored 0-21 higher=more restraint), Disinhibition sub scale (scored 0-16 higher=more disinhibition), Hunger sub scale (scored 0-14 higher=more hunger)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm, higher=greater amount or frequency)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline reinforcing value of food as measured by the Power of Food Scale (PFS; range 1-5, higher=greater power of food)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline sensitivity to reward as measured by the Behavioral Inhibition/Activation Scale (BIS/BAS) (BIS subscale range 7-28, higher = greater inhibition; BAS reward responsiveness sub scale range 5-20, higher=greater reward responsiveness, etc)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline impulsivity as measured by The Barratt Impulsiveness Scale (BIS-15, range 15-60, higher= more impulsiveness)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline binge eating as measured by The Questionnaire on Eating and Weight Patterns (QEWP-5); Measure categorizes participants based on whether they may meet diagnostic criteria for binge eating disorder
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline craving frequency as measured by the Food Craving Q Trait - Reduced
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline emotional eating as measured by the Dutch Eating Behaviour Questionnaire (DEBQ)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline perceived barriers to healthy eating and physical activity (Scale by Welsh et al., 2012)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline Weight Efficacy Life-Style Questionnaire (WEL)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline SCI Exercise Self Efficacy Scale (ESES)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Randomization Ball and Crawford Social Support Scale
time frame: Randomization (week 0)
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline food addiction using the Yale Food Addiction Scale (YFAS)
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: The reinforcing efficacy of high- and low-calorie food
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline sleep hours survey
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline Perceived Stress Scale
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline anxiety as measured by the GAD-7
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 1: Baseline general mindfulness and acceptance as measured using the Philadelphia Mindfulness Scale
time frame: Baseline
description: Exploratory predictor variable - phase 1
measure: Phase 2: Change in blood pressure
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in pulse
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in waist circumference
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in triglycerides
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in HDL and LDL cholesterol
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in fasting blood sugar
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm)
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in quality of life as measured by the Impact of Weight on Quality of Life (IWQOL)
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
measure: Phase 2: Change in physical activity using the Paffenbarger Physical Activity Questionnaire
time frame: Week 0 (randomization) to week 24
description: Exploratory outcomes - phase 2
arm group label: Behavioral Treatment + Placebo
arm group type: Active Comparator
description: All participants will complete an initial 4-week behavioral treatment (BT) run-in. Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
arm group label: Behavioral Treatment + Medication
arm group type: Active Comparator
description: All participants will complete an initial 4-week behavioral treatment (BT) run-in. Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
intervention type: Behavioral
intervention name: Behavioral Treatment
description: Behavioral treatment (BT) for weight loss includes diet and physical activity recommendations and behavior therapy strategies. All participants will complete an initial 4-week BT run-in, delivered in individual, 20-30 minute weekly sessions. After the end of the run-in, participants will be offered an additional 24 weeks of 20-30 minute individual BT sessions, occurring weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits).
arm group label: Behavioral Treatment + Medication
arm group label: Behavioral Treatment + Placebo
other name: Lifestyle modification
other name: Behavioral weight loss
intervention type: Drug
intervention name: Placebo
description: The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
arm group label: Behavioral Treatment + Placebo
other name: Placebo for medication
intervention type: Drug
intervention name: Phentermine 15 MG
description: The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
arm group label: Behavioral Treatment + Medication
other name: Medication
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jena S Tronieri, PhD
role: Principal Investigator
affiliation: Perelman School of Medicine at the University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: Weight Loss
mesh term: Phentermine
sharing ipd: Undecided
submitted: May 9, 2023
returned: June 6, 2023
submitted: August 29, 2023