Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment
Condition: Obesity
MeSH terms: Weight Loss
Study type: Interventional
Phase: Phase 4

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Behavioral Treatment; Placebo; Phentermine 15 MG
Intervention type(s): Behavioral; Drug; Drug
Intervention description(s): 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).; The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.; The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
Other intervention name(s): Lifestyle modification; Behavioral weight loss; Placebo for medication; Medication
Intervention MeSH terms: Phentermine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: phentermine; Hypoglycemic agents; Incretins; Hormones; Appetitive Behavior; Appetite Depressants; Anti-Obesity Agents; Weight Loss; Body Weight; Body Weight Changes; Signs and Symptoms