Predictors of Lorcaserin-Induced Weight Loss

• Sponsor: Columbia University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03353220
• Collaborator: New York State Psychiatric Institute (Other), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Overweight and Obesity	Drug: Belviq; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Central Mechanisms and Predictors of Lorcaserin-Induced Weight Loss
• Actual Study Start Date: Jan 3, 2018
• Actual Primary Completion Date: Feb 14, 2020
• Actual Study Completion Date: Feb 14, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo [First 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.

2. Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo [Baseline, 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

1. CSF Concentrations of ß-endorphin [Baseline, 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.

2. Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo [Baseline, 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.

3. Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo [Baseline, 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.

4. Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo [Baseline, 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.

5. Insulin Level [Changes 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• New York State Psychiatric Institute
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Sharon Wardlaw, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 29, 2021

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Sharon Wardlaw, Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT03353220
• Other Study ID Numbers: AAAR1622; 2R01DK093920
• First Posted: Nov 27, 2017
• Last Update Posted: Sep 23, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Sharon Wardlaw, Professor of Medicine, Columbia University: Overweight; Obesity; Weight Loss; Lorcaserin; Healthy Volunteers
• Additional relevant MeSH terms: Overweight; Weight Loss

Study Results

Participant Flow

Pre-assignment Detail

Out of the 32 enrolled subjects: 30 subjects completed Phase 1 (Arms A and B) and 30 subjects continued into Phase 2. However, the study was stopped prematurely during Phase 2 as lorcaserin was withdrawn from the market. Data was collected and analyzed for the 30 subjects that completed phase 1 out of 32 subjects; the 2 subjects who did not complete phase 1 were excluded from analysis. 19 subjects completed phase 2.

Arm/Group Title	Arm A (LOR-Placebo-LOR)	Arm B (Placebo-LOR-LOR)
Arm/Group Description	Phase 1: 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. Phase 2: Participants will receive additional lorcaserin (Belviq) for 24 weeks. Belviq: Belviq is an oral drug. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: 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. Phase 2: Participants will receive additional lorcaserin (Belviq) for 24 weeks. Belviq: Belviq is an oral drug. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.
Period Title: First Intervention (7 Days) - Phase 1
STARTED	14	16
COMPLETED	14	16
NOT COMPLETED	0	0
Period Title: First Intervention (7 Days) - Phase 1
STARTED	14	16
COMPLETED	14	16
NOT COMPLETED	0	0
Period Title: First Intervention (7 Days) - Phase 1
STARTED	14	16
COMPLETED	14	16
NOT COMPLETED	0	0
Period Title: First Intervention (7 Days) - Phase 1
STARTED	14	16
COMPLETED	10	9
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	Arm A+B (All Participants)
Arm/Group Description	Phase 1: Participants either receive lorcaserin (Belviq) 10 mg twice a day for 7 days followed by a 3 week washout period then cross over to receive placebo twice a day for 7 days (Arm A) OR receive placebo twice a day for 7 days followed by a 3 week washout period then cross over to receive lorcaserin (Belviq) 10 mg twice a day for 7 days (Arm B). Phase 2: Participants (from both arms) will receive additional lorcaserin (Belviq) for 24 weeks. Belviq: Belviq is an oral drug. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug. Belviq: Belviq is an oral drug Placebo: The placebo is made to mimic Belviq, but does not contain any active drug
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	28 87.5%
Male	4 12.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 37.5%
Not Hispanic or Latino	20 62.5%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo
Description	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.
Time Frame	First test meal and follow-up test meal (approximately up to 5 weeks)

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [kcal]	919.8 (118.7)	891.9 (109.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lorcaserin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	paired t test
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo
Description	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.
Time Frame	Baseline, up to 5 weeks

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [fmol/ml]	256.9 (18.5)	225.0 (15.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lorcaserin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	paired t test
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	CSF Concentrations of ß-endorphin
Description	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.
Time Frame	Baseline, up to 5 weeks

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [pg/ml]	49.07 (2.6)	55.8 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lorcaserin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments	paired t test
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo
Description	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.
Time Frame	Baseline, up to 5 weeks

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [pg/ml]	25.9 (3.0)	24.2 (3.1)

5. Secondary Outcome

Title	Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo
Description	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.
Time Frame	Baseline, up to 5 weeks

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [pg/ml]	78.7 (7.7)	79.2 (7.9)

6. Secondary Outcome

Title	Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo
Description	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.
Time Frame	Baseline, up to 5 weeks

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [pg/ml]	5.7 (0.22)	6.08 (0.33)

7. Secondary Outcome

Title	Insulin Level
Description	This is designed to determine effects of lorcaserin on glucose homeostasis by measuring changes in insulin levels after 1 week of lorcaserin versus placebo.
Time Frame	Changes in fasting serum insulin after 1 week of lorcaserin compared to placebo.

Outcome Measure Data

Analysis Population Description

The data information were collected and analyzed separately for the time period of placebo or drug exposure - i.e., comparing participants receiving placebo only OR Lorcaserin only (instead of comparing Arm A and Arm B). At one point, the same participant was exposed to either placebo OR Lorcaserin. Therefore, there are 30 analyzed for placebo only and 30 analyzed for drug only.

Arm/Group Title	Placebo	Lorcaserin
Arm/Group Description	Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.
Measure Participants	30	30
Mean (Standard Error) [µIU/ml]	20.1 (3.27)	13.2 (1.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lorcaserin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0189
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	LOR Time Period		Placebo Time Period
Arm/Group Description	Phase 1: These participants received lorcaserin (Belviq) 10 mg before the washout OR crossed over after the washout to receive lorcaserin twice a day for 7 days. Belviq: Belviq is an oral drug.		Phase 1: These participants either received placebo before the washout OR crossed over after washout to receive placebo twice a day for 7 days. Placebo: The placebo is made to mimic Belviq, but does not contain any active drug.
All Cause Mortality
	LOR Time Period		Placebo Time Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	LOR Time Period		Placebo Time Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	LOR Time Period		Placebo Time Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)

Limitations/Caveats

Study was stopped prematurely during Phase 2 due to lack of drug supply.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.