Clinical trial NCT02388568: Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
Official title: A Randomized Controlled Trial of Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2015-03-17
Enrollment: 137
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria (for the Randomized Controlled Trial)

1. Participants must have lost ≥ 5% of initial weight in the group lifestyle modification program (during the 14-week diet run-in period).
2. Participants must have a BMI ≥ 30 and ≤ 55 kg/m² or have a BMI ≥ 27 kg/m² with a obesity-related co-morbid condition
3. Age ≥ 21 years and ≤ 65
4. 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
5. 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:

1. Pregnant or nursing (or plans to become pregnant in the next 18 months)
2. Current major depressive episode, active suicidal ideation, or history of suicide attempts
3. 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
4. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg, or diastolic blood pressure ≥ 100 mm Hg)
5. Type 1 diabetes or type 2 diabetes
6. A fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5
7. 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
8. Clinically significant hepatic or renal disease
9. Thyroid disease not controlled
10. History of malignancy (except for non-melanoma skin cancer)
11. Use of medications known to induce significant weight loss/gain, including chronic use of oral steroids
12. Psychiatric hospitalization within the past 6 months
13. Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
14. Loss of ≥ 10 lb of body weight within the past 3 months
15. History of (or plans for) bariatric surgery

Primary outcomes:
measure: Change in Weight (kg)
timeFrame: 52 weeks post-randomization
measure: Proportion Maintaining >= 5% Loss of Initial Weight
timeFrame: 52 weeks post-randomization
Secondary outcomes:
measure: Body Weight (% Change)
timeFrame: 52 weeks post-randomization
measure: Proportion Maintaining >= 10% Loss of Initial Weight
timeFrame: 52 weeks post-randomization
measure: Body Weight
timeFrame: -14 week (start of LCD program) to week 52
measure: Body Weight (% Change)
timeFrame: -14 week (start of LCD program) to week 52
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Center for Weight and Eating Disorders
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Thomas A Wadden, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Robert I Berkowitz, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pearl RL, Wadden TA, Chao AM, Walsh O, Alamuddin N, Berkowitz RI, Tronieri JS. Weight Bias Internalization and Long-Term Weight Loss in Patients With Obesity. Ann Behav Med. 2019 Jul 17;53(8):782-787. doi: 10.1093/abm/kay084.
citation: Pearl RL, Wadden TA, Allison KC, Chao AM, Alamuddin N, Berkowitz RI, Walsh O, Tronieri JS. Causal Attributions for Obesity Among Patients Seeking Surgical Versus Behavioral/Pharmacological Weight Loss Treatment. Obes Surg. 2018 Nov;28(11):3724-3728. doi: 10.1007/s11695-018-3490-7.
citation: Pearl RL, Wadden TA, Tronieri JS, Berkowitz RI, Chao AM, Alamuddin N, Leonard SM, Carvajal R, Bakizada ZM, Pinkasavage E, Gruber KA, Walsh OA, Alfaris N. Short- and Long-Term Changes in Health-Related Quality of Life with Weight Loss: Results from a Randomized Controlled Trial. Obesity (Silver Spring). 2018 Jun;26(6):985-991. doi: 10.1002/oby.22187. Epub 2018 Apr 20.
citation: Shaw Tronieri J, Wadden TA, Berkowitz RI, Chao AM, Pearl RL, Alamuddin N, Leonard SM, Carvajal R, Bakizada ZM, Pinkasavage E, Gruber KA, Walsh OA, Alfaris N. A Randomized Trial of Lorcaserin and Lifestyle Counseling for Maintaining Weight Loss Achieved with a Low-Calorie Diet. Obesity (Silver Spring). 2018 Feb;26(2):299-309. doi: 10.1002/oby.22081. Epub 2017 Dec 29.
citation: Tronieri JS, Alfaris N, Chao AM, Pearl RL, Alamuddin N, Bakizada ZM, Berkowitz RI, Wadden TA. Lorcaserin plus lifestyle modification for weight loss maintenance: Rationale and design for a randomized controlled trial. Contemp Clin Trials. 2017 Aug;59:105-112. doi: 10.1016/j.cct.2017.06.004. Epub 2017 Jun 16.
citation: Pearl RL, Wadden TA, Hopkins CM, Shaw JA, Hayes MR, Bakizada ZM, Alfaris N, Chao AM, Pinkasavage E, Berkowitz RI, Alamuddin N. Association between weight bias internalization and metabolic syndrome among treatment-seeking individuals with obesity. Obesity (Silver Spring). 2017 Feb;25(2):317-322. doi: 10.1002/oby.21716.