Lifestyle Modification and Lorcaserin for Weight Loss Maintenance

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Controlled Trial of Lifestyle Modification and Lorcaserin for Weight Loss Maintenance

Conditions
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Obesity

Intervention / Treatment
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* Drug: Lorcaserin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (for the Randomized Controlled Trial) Participants must have lost ≥ 5% of initial weight in the group lifestyle modification program (during the 14-week diet run-in period). Participants must have a BMI ≥ 30 and ≤ 55 kg/m² or have a BMI ≥ 27 kg/m² with a obesity-related co-morbid condition Age ≥ 21 years and ≤ 65 Eligible female patients will be: non-pregnant, evidenced by a negative urine dipstick pregnancy test non-lactating surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study Participants must have a primary care provider (PCP) who is responsible for providing routine care and have a reliable telephone service with which to participate in conference calls Exclusion Criteria: Pregnant or nursing (or plans to become pregnant in the next 18 months) Current major depressive episode, active suicidal ideation, or history of suicide attempts Use in the past 14 days of monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclics, lithium, triptans, antipsychotics, cabergoline, linezolid, tramadol, dextromethorphan, tryptophan, bupropion, St. John's Wort, or medicines to treat erectile dysfunction Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg, or diastolic blood pressure ≥ 100 mm Hg) Type 1 diabetes or type 2 diabetes A fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5 Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree Clinically significant hepatic or renal disease Thyroid disease not controlled History of malignancy (except for non-melanoma skin cancer) Use of medications known to induce significant weight loss/gain, including chronic use of oral steroids Psychiatric hospitalization within the past 6 months Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week) Loss of ≥ 10 lb of body weight within the past 3 months History of (or plans for) bariatric surgery

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lorcaserin plus Lifestyle Modification<br> | Drug: Lorcaserin<br>* Lorcaserin plus Lifestyle Modification<br>|
| Placebo Comparator: Placebo plus Lifestyle Modification<br> | Drug: Placebo<br>* Placebo plus Lifestyle Modification<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight (kg) | This is the change in weight from randomization to week 52. This does not include the weight loss in the 14-week LCD. | 52 weeks post-randomization | 
| Proportion Maintaining >= 5% Loss of Initial Weight | This is the number of participants who maintained >=5% loss of initial weight in the randomization to week 52 trial period. | 52 weeks post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight (% Change) | The % change in body weight from randomization to week 52. | 52 weeks post-randomization | 
| Proportion Maintaining >= 10% Loss of Initial Weight | This is the number of participants who maintained >=10% loss of initial weight in the randomization to week 52 trial period. | 52 weeks post-randomization | 
| Body Weight | This is the change in weight from baseline (screening visit) to the final week 52 medical assessment visit. | -14 week (start of LCD program) to week 52 | 
| Body Weight (% Change) | This is the change in weight from the baseline (screening visit) to the final week 52 medical assessment visit. | -14 week (start of LCD program) to week 52 |