Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
Condition: Obesity
MeSH terms: Weight Loss
Study type: Interventional

Summary: 
      The proposed 12-month randomized controlled trial will assess the efficacy of lifestyle
      counseling, combined with lorcaserin (10 mg BID) or placebo, in maintaining weight loss
      achieved during a prior 14-week dietary run-in.

      14-week run-in. To qualify for randomization, participants must lose ≥5% of initial weight in
      the 14-week dietary run-in. This loss will be achieved with the provision of weekly, group
      lifestyle counseling, which includes a 1000-1200 kcal/day portion-controlled diet that
      combines four daily servings of a liquid diet (HMR shakes) with an evening meal of a
      frozen-food entree (and a fruit and vegetable serving). More than 70% of participants are
      expected to achieve the 5% criterion loss during the 14-week run-in.

      A total of 182 women and men with a BMI ≥33 and ≤55 kg/m2, without co-morbidities, or ≥30 and
      ≤55 kg/m2 (with a co-morbid cardiovascular disease (CVD) condition) will be enrolled in the
      4-month run-in period. Prior to enrollment, all participants will have a history, physical
      exam, electrocardiogram (EKG), and appropriate blood tests. They will attend weekly group
      sessions for 14 weeks. Participants will have a brief medical visit at week 8 to check their
      health and blood tests will be repeated. The investigators anticipate that 136 (75%)
      participants will lose 5% or more of initial weight and qualify for randomization.
      Participants who do not lose 5% will be provided a list of weight loss resources (e.g., other
      programs) to facilitate their continued weight management.

      12-month randomized trial with lorcaserin. A total of 136 participants who have lost 5% or
      more of initial weight in the run-in period will be randomly assigned, in double-blind
      fashion, to lorcaserin (10 mg BID) or matching placebo. To be eligible, participants must
      have a BMI (after prior weight loss) ≥30 kg/m2 (without co-morbidities) or greater than or
      equal to ≥27 (with a co-morbidity). Randomization will be performed by the Investigational
      Drug Service at the Hospital of the University of Pennsylvania. Prior to randomization, all
      participants will complete a second brief history and physical examination, as well as an EKG
      and blood tests. Medication will be dispensed at the randomization visit and at brief medical
      visits that follow. Over the 1 year, all participants will participate in 16 group lifestyle
      modification classes designed for weight loss maintenance, approximately half of which will
      be delivered by group conference call.

      Primary outcome measure. The primary endpoint is change in body weight (in kg), as measured
      from randomization to month 12. The co-primary end-point is the percentage of participants in
      the two groups that, at month 12, maintained the ≥5% reduction in body weight achieved during
      the 14-week dietary run-in period. Secondary efficacy endpoints include changes in CVD risk
      factors, glycemic control, and quality of life, as measured from randomization to month 12.
      Exploratory endpoints include changes in these CVD and related outcomes, as measured at the
      start of the 14-week run-in period to month 12. The investigators also will examine the
      percentage of participants in the two groups who at month 12 achieved losses of ≥5%, ≥10%,
      and ≥15% of initial weight, as measured from the start of the run-in period.

      Safety endpoints will include physical examination, electrocardiogram, adverse events (AEs),
      standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity
      Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

      Statistical Analysis. The planned sample size of 136 participants, with a 1:1 randomization
      ratio, assumes a 20% drop-out rate (at month 12) and was estimated to be adequate to evaluate
      the primary endpoint with power ≥90% (P=0.05, two-sided test). The investigators predict a
      difference in weight change between the two groups (from randomization to month 12) of 4 kg
      (SD=3.5). Pre-specified data analysis will be performed on the full analysis set, comprising
      all randomized individuals exposed to trial drug with at least one post-randomization weight
      assessment.
    


Intervention name(s): Lorcaserin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Lorcaserin plus Lifestyle Modification; Placebo plus Lifestyle Modification
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment