Overweight and Obesity
Conditions
Keywords
Overweight, Obesity, Weight Loss, Lorcaserin, Healthy Volunteers
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.
Interventions
DRUGBelviq
Belviq is an oral drug
DRUGPlacebo
The placebo is made to mimic Belviq, but does not contain any active drug
Sponsors
New York State Psychiatric Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Arm A+B (All Participants) 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 | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Third Intervention (6 Months) - Phase 2 | Study was stopped due to unavailable study drug supply | 4 | 7 |
Baseline characteristics
| Characteristic | Arm A+B (All Participants) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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.
Time frame: First test meal and follow-up test meal (approximately up to 5 weeks)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo | 919.8 kcal | Standard Error 118.7 |
| Lorcaserin | Mean Differences in Food Intake During a Laboratory Test Meal After Lorcaserin for One Week Compared to Placebo | 891.9 kcal | Standard Error 109 |
p-value: 0.65t-test, 2 sided
Primary
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.
Time frame: Baseline, up to 5 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 256.9 fmol/ml | Standard Error 18.5 |
| Lorcaserin | Mean Differences in POMC Concentrations (Fmol/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 225.0 fmol/ml | Standard Error 15.9 |
p-value: 0.0001t-test, 2 sided
Secondary
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.
Time frame: Baseline, up to 5 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CSF Concentrations of ß-endorphin | 49.07 pg/ml | Standard Error 2.6 |
| Lorcaserin | CSF Concentrations of ß-endorphin | 55.8 pg/ml | Standard Error 3.2 |
p-value: 0.0017t-test, 2 sided
Secondary
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.
Time frame: Changes in fasting serum insulin after 1 week of lorcaserin compared to placebo.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Insulin Level | 20.1 µIU/ml | Standard Error 3.27 |
| Lorcaserin | Insulin Level | 13.2 µIU/ml | Standard Error 1.16 |
p-value: 0.0189t-test, 2 sided
Secondary
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.
Time frame: Baseline, up to 5 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo | 78.7 pg/ml | Standard Error 7.7 |
| Lorcaserin | Mean Differences in AgRP Concentrations (Fmol/ml) in Blood After Lorcaserin for One Week Compared to Placebo | 79.2 pg/ml | Standard Error 7.9 |
Secondary
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.
Time frame: Baseline, up to 5 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 25.9 pg/ml | Standard Error 3 |
| Lorcaserin | Mean Differences in AgRP Concentrations (pg/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 24.2 pg/ml | Standard Error 3.1 |
Secondary
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.
Time frame: Baseline, up to 5 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 5.7 pg/ml | Standard Error 0.22 |
| Lorcaserin | Mean Differences in Cortisol Concentrations (ng/ml) in CSF After Lorcaserin for One Week Compared to Placebo | 6.08 pg/ml | Standard Error 0.33 |