Clinical trial NCT03353220: Predictors of Lorcaserin-Induced Weight Loss
Official title: Central Mechanisms and Predictors of Lorcaserin-Induced Weight Loss
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Overweight and Obesity
Keywords: Overweight
Obesity
Weight Loss
Lorcaserin
Healthy Volunteers
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: New York State Psychiatric Institute
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-11-27
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo
timeFrame: First test meal and follow-up test meal (approximately up to 5 weeks)
measure: Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo
timeFrame: Baseline, up to 5 weeks
Secondary outcomes:
measure: CSF Concentrations of ß-endorphin
timeFrame: Baseline, up to 5 weeks
measure: Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo
timeFrame: Baseline, up to 5 weeks
measure: Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo
timeFrame: Baseline, up to 5 weeks
measure: Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo
timeFrame: Baseline, up to 5 weeks
measure: Insulin Level
timeFrame: Changes in fasting serum insulin after 1 week of lorcaserin compared to placebo.
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Sharon Wardlaw, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.