Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 21 - 65 |
| Updated: | 6/13/2018 |
| Start Date: | January 2015 |
| End Date: | June 2017 |
A Randomized Controlled Trial of Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
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.
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.
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
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