Predictors of Lorcaserin-Induced Weight Loss

Central Mechanisms and Predictors of Lorcaserin-Induced Weight Loss

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).

Study Overview

• Status: Terminated
• Conditions: Overweight and Obesity
• Intervention / Treatment: Drug: Belviq; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body Mass Index (BMI) 28-40

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants 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.	Drug: Belviq; Belviq is an oral drug; Other Names: Lorcaserin; Drug: Placebo; The placebo is made to mimic Belviq, but does not contain any active drug
Experimental: Arm B; Participants 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.	Drug: Belviq; Belviq is an oral drug; Other Names: Lorcaserin; Drug: Placebo; The placebo is made to mimic Belviq, but does not contain any active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo	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.	First test meal and follow-up test meal (approximately up to 5 weeks)
Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo	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.	Baseline, up to 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF Concentrations of ß-endorphin	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.	Baseline, up to 5 weeks
Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo	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.	Baseline, up to 5 weeks
Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo	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.	Baseline, up to 5 weeks
Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo	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.	Baseline, up to 5 weeks
Insulin Level	This is designed to determine effects of lorcaserin on glucose homeostasis by measuring changes in insulin levels after 1 week of lorcaserin versus placebo.	Changes in fasting serum insulin after 1 week of lorcaserin compared to placebo.

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); New York State Psychiatric Institute
• Investigators: Principal Investigator: Sharon Wardlaw, MD, Columbia University

Publications and helpful links

General Publications

• Sideri Gugger A, Dimino C, Panigrahi SK, Mayer L, Smiley RM, Korner J, Wardlaw SL. Defining Predictors of Weight Loss Response to Lorcaserin. J Clin Endocrinol Metab. 2023 Aug 18;108(9):2262-2271. doi: 10.1210/clinem/dgad139.

Helpful Links

• NIH - lorcaserin HCl
• Study Grant
• FDA approval Belviq

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): February 14, 2020

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Healthy Volunteers; Weight Loss; Lorcaserin
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Body Weight Changes; Weight Loss; Overweight
• Other Study ID Numbers: AAAR1622; 2R01DK093920 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No