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| Name | Class |
|---|---|
| American Heart Association | OTHER |
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This project tests the principle hypothesis that stable glucagon like peptide-1 (GLP-1) analogues have specific GLP1R-dependent beneficial effects on vascular endothelial function, fibrinolysis and inflammation in obesity that exceed the benefits of weight loss, and that genetic or other individual factors that modulate GLP1R sensitivity can modify the effect of these analogues on cardiovascular risk.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| liraglutide | Experimental | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. |
|
| sitagliptin | Active Comparator | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. |
|
| hypocaloric diet | Active Comparator | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liraglutide | Drug | subcutaneous liraglutide daily |
| |
| Sitagliptin |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Flow-mediated Dilation | Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %) | Baseline to 2 and 14 weeks |
| Urine Albumin-to-creatinine Ratio | Ratio of urine albumin to creatinine in a spot urine collected after overnight rest | Baseline to 13 weeks |
| Change in Plasminogen Activator Inhibitor-1 | Plasma plasminogen activator inhibitor-1 antigen | Baseline to 2 and 14 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Pressure | The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position | Baseline, and after 2 weeks and 14 weeks of treatment |
| Heart Rate |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Weight | Weight measured in light clothing without shoes | Change from baseline to 14 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James M. Luther, M.D. | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
Not provided
| Label | URL |
|---|---|
| Study Pre-print on medRxiv | View source |
Not provided
Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.
The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.
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CONSORT flow details:
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| ID | Title | Description |
|---|---|---|
| FG000 | Liraglutide | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| FG001 | Sitagliptin | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| FG002 | Hypocaloric Diet | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Liraglutide | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Flow-mediated Dilation | Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %) | Incomplete data due to missed study visits and missing samples in the following time periods/arms (n= number of participants with missing data):
| Posted | Mean | Standard Deviation | Percentage | Baseline to 2 and 14 weeks |
|
After randomization to 14 weeks
Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant, including any abnormal sign, symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. Adverse events were collected from the time of randomization through participant completion at each screening visit, study day, and at week 4, week 8 and week 12 check-ins.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Liraglutide | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis/abscess | Skin and subcutaneous tissue disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
Study enrollment and conduct interrupted due to COVID-19 pandemic. Exendin not available for all study participants.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James M. Luther, MD MSCI (Principal Investigator) | Vanderbilt University Medical Center | (615) 936-3420 | james.luther@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 2, 2021 | Jun 21, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069450 | Liraglutide |
| D000068900 | Sitagliptin Phosphate |
| C083773 | exendin (9-39) |
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
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Treatment with liraglutide or sitagliptin will be masked using matching placebo.
| Drug |
oral sitagliptin daily |
|
| hypocaloric diet | Other | Reduced calorie intake to achieve weight loss. |
|
| Placebos | Drug | Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. |
|
| Exendin (9-39) | Drug | All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
|
The mean of three measurements with the patient in the supine position
| Baseline, and after 2 weeks and 14 weeks of treatment |
| Fasting Glucose | Blood glucose collected after overnight fast | Baseline, and after 2 weeks and 14 weeks of treatment |
| Fasting Insulin | Plasma insulin collected after overnight fast | Baseline, and after 2 weeks and 14 weeks of treatment |
| BG001 | Sitagliptin | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| BG002 | Hypocaloric Diet | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Flow mediated dilation | Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide 4, Sitaglipin 1, Hypocaloric Diet 3 | Mean | Standard Deviation | Percentage |
|
| Urine Albumin-Creatinine ratio | mg albumin/g creatinine | Participants who were randomized to intervention but did not complete study day measurements are not included: Liraglutide 2, Sitagliptin 1, Hypocaloric Diet 2 | Mean | Standard Deviation | mg/g |
|
| Plasminogen Activator Inhibitor-1, plasma | plasma PAI-1 (U/mL) | Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide 3, Sitaglipin 2, Hypocaloric Diet 4 | Mean | Standard Deviation | U/mL |
|
| OG001 | Sitagliptin | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| OG002 | Hypocaloric Diet | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
|
|
| Primary | Urine Albumin-to-creatinine Ratio | Ratio of urine albumin to creatinine in a spot urine collected after overnight rest | Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: 2 participants; Diet: 6 participants | Posted | Mean | Standard Deviation | mg/g | Baseline to 13 weeks |
|
|
|
| Primary | Change in Plasminogen Activator Inhibitor-1 | Plasma plasminogen activator inhibitor-1 antigen | Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: Baseline: 2 participants/Week 14: 3 participants; Sitagliptin: Baseline: 1 participants/Week 14: 1 participants; Diet: Baseline: 3 participants/Week 14: 6 participants | Posted | Mean | Standard Deviation | units/mL | Baseline to 2 and 14 weeks |
|
|
|
| Secondary | Blood Pressure | The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position | Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide 14 weeks- 2 participants; Diet 14 weeks: 5 participants | Posted | Mean | Standard Deviation | mmHg | Baseline, and after 2 weeks and 14 weeks of treatment |
|
|
|
| Secondary | Heart Rate | The mean of three measurements with the patient in the supine position | Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide 14 weeks- 2 participants; Diet 14 weeks: 5 participants | Posted | Mean | Standard Deviation | Beats per minute | Baseline, and after 2 weeks and 14 weeks of treatment |
|
|
|
| Secondary | Fasting Glucose | Blood glucose collected after overnight fast | Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide Baseline-1, 2 weeks 1, 14 weeks- 2 participants; Sitagliptin 2 weeks 1, 14 weeks- 1 participants; Diet 14 weeks: 5 participants | Posted | Mean | Standard Deviation | mg/dl | Baseline, and after 2 weeks and 14 weeks of treatment |
|
|
|
| Secondary | Fasting Insulin | Plasma insulin collected after overnight fast | Due to missed study visits or missing data there is incomplete data for the following arms/time periods: Liraglutide 2 weeks 3, 14 weeks- 3 participants; Sitagliptin 2 weeks 2, 14 weeks- 1 participants; Diet 14 weeks: 5 participants | Posted | Mean | Standard Deviation | uU/mL | Baseline, and after 2 weeks and 14 weeks of treatment |
|
|
|
| Other Pre-specified | Change in Weight | Weight measured in light clothing without shoes | Due to missed study visits or missing data there is incomplete data for the following arms/time periods: Liraglutide 2 participants; Diet 5 participants | Posted | Mean | Standard Deviation | kg | Change from baseline to 14 weeks |
|
|
|
| 0 |
| 46 |
| 0 |
| 46 |
| 26 |
| 46 |
| EG001 | Sitagliptin | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | 0 | 23 | 1 | 23 | 6 | 23 |
| EG002 | Hypocaloric Diet | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | 0 | 24 | 1 | 24 | 6 | 24 |
| Nephrolithiasis and hydronephrosis | Renal and urinary disorders | Systematic Assessment |
|
| Diverticulitis | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Study day procedure adverse event | Surgical and medical procedures | Systematic Assessment | Including nausea or abdominal pain from mixed meal tolerance test, pain from ultrasound flow-mediated dilation technique or from subcutaneous adipose tissue liposuction, headache from nitroglycerin administration. |
|
| Injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Lightheaded | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Nervous system disorders | Systematic Assessment |
|
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 13 Weeks |
|
|
| Baseline to 14 weeks |
|
|
| 2 weeks |
|
|
| 14 weeks |
|
|
| 2 weeks |
|
|
| 14 weeks |
|
|
| 2 weeks |
|
|
| 14 weeks |
|
|
| 2 weeks |
|
|
| 14 weeks |
|
|