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Predictors of Lorcaserin-Induced Weight Loss

Phase 4
Terminated
Conditions
Overweight and Obesity
Interventions
Drug: Belviq
Drug: Placebo
Registration Number
NCT03353220
Lead Sponsor
Columbia University
Brief Summary

This two-phase study aims to explore ways to predict who will respond well to the weight loss drug lorcaserin and to understand the mechanisms that develop which limit drug efficacy. Subjects will be recruited for a 5-week crossover study (phase 1) with lorcaserin and placebo followed by treatment with lorcaserin for 24 weeks (phase 2).

Detailed Description

In phase 1, at Weeks 1 and 5, participants will take the weight loss drug lorcaserin or placebo for 7 days. At Week 5 participants will receive whichever treatment they did not receive at Week 1. At the end of Weeks 1 and 5, participants will have a lumbar puncture (spinal tap) to collect cerebrospinal fluid (CSF) for neuropeptide and hormone analyses, including proopiomelanocortin (POMC), Agouti-related protein (AgRP) and cortisol. Blood will also be obtained for neuropeptide and hormone analyses. Breakfast will be served to participants who will then complete an eating behavior profile. A laboratory test meal will be performed 4h after breakfast.

After completing both the 7 day lorcaserin and placebo studies, participants will then continue on Phase 2 of the study, which includes treatment with lorcaserin for 24 weeks. Subjects will receive nutritional counseling to reduce their daily caloric intake to 600 kcal below their calculated caloric requirement and will be encourage to exercise moderately for 30 minutes daily. Participants will visit the clinic monthly during the 24 week study period for nutritional counseling, review of food diaries, vital signs and safely labs. Blood will also be obtained for neuropeptide peptide and hormone analyses. At the end of the 24 week period subjects will come for a final study visit, including a lumbar puncture, blood sample, breakfast, an eating behavior profile and a test meal.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • Body Mass Index (BMI) 28-40
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Exclusion Criteria
  • Any clinically significant or relevant medical condition, including:
  • Diabetes
  • Uncontrolled Hypertension
  • Heart disease
  • Bleeding disorder
  • Kidney or liver dysfunction
  • Neurologic disease
  • Psychiatric or eating disorders
  • Pregnancy or breastfeeding
  • Use of tobacco or opiates
  • History of alcohol or drug abuse
  • Recent weight change +/- 5%
  • Medications that affect body weight
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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Arm ABelviqParticipants receive lorcaserin (Belviq) 10 mg twice a day for 7 days followed by a 3 week washout period. These participants will then be crossed over to receive placebo twice a day for 7 days.
Arm BBelviqParticipants receive placebo twice a day for 7 days followed by a 3 week washout period. These participants will then be crossed over to receive lorcaserin (Belviq)10 mg twice a day for 7 days.
Arm BPlaceboParticipants receive placebo twice a day for 7 days followed by a 3 week washout period. These participants will then be crossed over to receive lorcaserin (Belviq)10 mg twice a day for 7 days.
Arm APlaceboParticipants receive lorcaserin (Belviq) 10 mg twice a day for 7 days followed by a 3 week washout period. These participants will then be crossed over to receive placebo twice a day for 7 days.
Primary Outcome Measures
NameTimeMethod
Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to PlaceboFirst test meal and follow-up test meal (approximately up to 5 weeks)

This is designed to measure food Intake (average calories consumed during test meal), in order to determine if long-term lorcaserin induced weight loss is predicted by the short-term differences in calories consumed during the test meal.

Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to PlaceboBaseline, up to 5 weeks

This is designed to measure mean CSF proopiomelanocortin (POMC) concentrations (fmol/ml), in order to determine if long-term lorcaserin induced weight loss can be predicted by differences in CSF POMC concentrations.

Secondary Outcome Measures
NameTimeMethod
CSF Concentrations of ß-endorphinBaseline, up to 5 weeks

Mean differences in levels of ß-endorphin, a POMC-derived peptide, in CSF after lorcaserin for one week compared to placebo in order to determine if long-term lorcaserin induced weight loss can be predicted using short-term differences in CSF concentrations of ß-endorphin.

Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to PlaceboBaseline, up to 5 weeks

This is designed to measure mean mean Agouti-related protein (AgRP) concentrations (pg/ml) in CSF in blood in order to determine if long-term lorcaserin induced weight loss can be predicted by short-term differences in AgRP concentrations.

Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to PlaceboBaseline, up to 5 weeks

This is designed to measure mean Agouti-related protein (AgRP) concentrations (fmol/ml) in blood in order to determine if long-term lorcaserin induced weight loss can be predicted by short-term differences in AgRP concentrations.

Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to PlaceboBaseline, up to 5 weeks

This is designed to measure mean Cortisol concentrations (ng/ml) in CSF in order to determine if long-term lorcaserin induced weight loss can be predicted by short-term differences in cortisol concentrations.

Insulin LevelChanges in fasting serum insulin after 1 week of lorcaserin compared to placebo.

This is designed to determine effects of lorcaserin on glucose homeostasis by measuring changes in insulin levels after 1 week of lorcaserin versus placebo.

Trial Locations

Locations (1)

Columbia University Medical Center

🇺🇸

New York, New York, United States

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