Obesity
Conditions
Brief summary
This study is being done to assess the stomach emptying effect of a maximum dose of 3 mg Liraglutide compared to placebo in subjects who are overweight or obese. Liraglutide is a medication approved by the Food and Drug Administration (FDA) for routine clinical use.
Interventions
DRUGLiraglutide
Initiate at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6mg/day in weekly intervals to a dose of 3.0 mg/day is achieved (\ 4 weeks). Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication.
DRUGPlacebo
Placebo administration will match the study drug.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Novo Nordisk A/S
Michael Camilleri, MD
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overweight and obese adults (≥30 kg/m\^2 or ≥27 kg/m\^2 with an obesity-related co-morbidity). * Subjects residing within 125 miles of Mayo Clinic in Rochester, Minnesota. * Healthy individuals with no unstable psychiatric disease and not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, or endocrine (other than hyperglycemia type 2 diabetes mellitus on metformin) disorders. * The investigators plan to recruit equal proportions of men and women. * Women of childbearing potential will be using an effective form of contraception, and have negative pregnancy tests within 48 hours of enrollment and before each radiation exposure. In addition, since liraglutide 3.0 mg is classified as Pregnancy Category X, monthly urine pregnancy testing will be performed in any female participant with childbearing potential. * Subjects must have the ability to provide informed consent before any trial-related activities.
Exclusion criteria
* Weight exceeding 137 kilograms (safety limit of camera for measuring gastric volumes). * Abdominal surgery other than appendectomy, cholecystectomy, Caesarian section or tubal ligation. * Positive history of chronic gastrointestinal diseases, systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption, e.g., orlistat. * Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia-type 2. * Patients with a past or current history of pancreatitis, gallstones, history of alcoholism, blood triglyceride levels \>500 mg/dL. * Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), a self-administered alcoholism screening test (AUDIT-C), and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a HAD score \>11 on either the Anxiety or Depression subscales, or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up. * Intake of any medication (except multivitamins), within 7 days of the study. Exceptions are birth control pill, estrogen replacement therapy, thyroxin replacement therapy and any medication administered for co-morbidities as long as they do not alter gastrointestinal motility including gastric emptying (GE) and gastric accommodation. For example, statins for hyperlipidemia, diuretics, β-adrenergic blockers, Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin antagonists for hypertension, and metformin for type 2 diabetes mellitus or prediabetes are permissible. In contrast, resin sequestrants for hyperlipidemia (which may reduce GE and reduce appetite, α2-adrenergic agonists for hypertension, or other glucagon-like peptide-1 receptor agonists (GLP-1) receptor agonists (exenatide) or amylin analogs (pramlintide) are not permissible because they significantly affect GE and/or gastric accommodation. * Delayed gastric emptying at 2 and 4 hours * Hypersensitivity to the study medication, liraglutide * Participate in highly intense physical activity program that could potentially interfere with study interpretation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Emptying of Solids (T1/2) | 5 weeks | The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi), gastric emptying of solids was assessed with scintigraphy imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight at 16 Weeks | baseline, 16 weeks | Change in subject's weight, in kilograms |
| Satiety | 16 weeks | Subjects self-reported fullness after eating as much of a prescribed meal measured by kilocalories of food consumed. |
| Satiation Volume to Fullness | 16 weeks | Subjects ingest Ensure 300mL drink meal at a constant rate of 30mL/min until self-reported fullness and volume consumed will be measured in milliliters (mL). |
| Change in Weight at 5 Weeks | baseline, 5 weeks | Change in subject's weight, in kilograms |
| Fasting Gastric Volume Prior to Meal | 16 weeks | Gastric fasting volume was measured prior to a meal of 300 mL Ensure drink using noninvasive single photon emission-computed tomography (SPECT) of the stomach. |
| Gastric Volume After Meal | 16 weeks | Gastric volume was measured after a meal of 300 mL Ensure drink using noninvasive single photon emission-computed tomography (SPECT) of the stomach. |
| Gastric Accommodation | 16 weeks | Measured in milliliters (mL), using the difference between the fasting gastric volume prior to the meal and the gastric volume after the meal. |
| Maximum Satiation | 16 weeks | Subjects ingest Ensure 300mL drink meal at a constant rate of 30mL/min until they reach maximum or unbearable fullness. Volume consumed will be measured in milliliters (mL). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide Liraglutide initiated at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6 mg/day in weekly intervals to a dose of 3.0 mg/day is achieved. Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication. | 67 |
| Placebo Placebo initiated at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6 mg/day in weekly intervals to a dose of 3.0 mg/day is achieved. Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication. | 69 |
| Total | 136 |
Baseline characteristics
| Characteristic | Liraglutide | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 42 years | 37.7 years | 37.2 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) White | 60 Participants | 125 Participants | 65 Participants |
| Region of Enrollment United States | 67 participants | 136 participants | 69 participants |
| Sex: Female, Male Female | 59 Participants | 118 Participants | 59 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 69 |
| other Total, other adverse events | 67 / 67 | 56 / 69 |
| serious Total, serious adverse events | 1 / 67 | 1 / 69 |
Outcome results
Primary
Gastric Emptying of Solids (T1/2)
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi), gastric emptying of solids was assessed with scintigraphy imaging.
Time frame: 5 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Gastric Emptying of Solids (T1/2) | 191.6 minutes |
| Placebo | Gastric Emptying of Solids (T1/2) | 105.9 minutes |
Primary
Gastric Emptying of Solids (T1/2)
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi), gastric emptying of solids was assessed with scintigraphy imaging.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Gastric Emptying of Solids (T1/2) | 154.4 minutes |
| Placebo | Gastric Emptying of Solids (T1/2) | 111.4 minutes |
Secondary
Change in Weight at 16 Weeks
Change in subject's weight, in kilograms
Time frame: baseline, 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Change in Weight at 16 Weeks | -5.8 kilograms |
| Placebo | Change in Weight at 16 Weeks | 0.0 kilograms |
p-value: 0.033Wilcoxon (Mann-Whitney)
Secondary
Change in Weight at 5 Weeks
Change in subject's weight, in kilograms
Time frame: baseline, 5 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Change in Weight at 5 Weeks | -3.8 kilograms |
| Placebo | Change in Weight at 5 Weeks | 0.1 kilograms |
p-value: 0.004Wilcoxon (Mann-Whitney)
Secondary
Fasting Gastric Volume Prior to Meal
Gastric fasting volume was measured prior to a meal of 300 mL Ensure drink using noninvasive single photon emission-computed tomography (SPECT) of the stomach.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Fasting Gastric Volume Prior to Meal | 221.2 milliliters (mL) |
| Placebo | Fasting Gastric Volume Prior to Meal | 191.5 milliliters (mL) |
Secondary
Gastric Accommodation
Measured in milliliters (mL), using the difference between the fasting gastric volume prior to the meal and the gastric volume after the meal.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Gastric Accommodation | 385.4 milliliters (mL) |
| Placebo | Gastric Accommodation | 391.8 milliliters (mL) |
Secondary
Gastric Volume After Meal
Gastric volume was measured after a meal of 300 mL Ensure drink using noninvasive single photon emission-computed tomography (SPECT) of the stomach.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Gastric Volume After Meal | 629.1 milliliters (mL) |
| Placebo | Gastric Volume After Meal | 583.8 milliliters (mL) |
Secondary
Maximum Satiation
Subjects ingest Ensure 300mL drink meal at a constant rate of 30mL/min until they reach maximum or unbearable fullness. Volume consumed will be measured in milliliters (mL).
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Maximum Satiation | 974.4 milliliters (mL) |
| Placebo | Maximum Satiation | 1119.8 milliliters (mL) |
Secondary
Satiation Volume to Fullness
Subjects ingest Ensure 300mL drink meal at a constant rate of 30mL/min until self-reported fullness and volume consumed will be measured in milliliters (mL).
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Satiation Volume to Fullness | 622.1 milliliters (mL) |
| Placebo | Satiation Volume to Fullness | 746.6 milliliters (mL) |
Secondary
Satiety
Subjects self-reported fullness after eating as much of a prescribed meal measured by kilocalories of food consumed.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liraglutide | Satiety | 647.5 kilocalories |
| Placebo | Satiety | 793.7 kilocalories |