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Trial · Interventional

CompletedPhase 4Results postedRegistry data

Cardiovascular Effects of GLP-1 Receptor Activation

Overview

Status
Completed
Phase
Phase 4
Enrollment
329 participants (actual)
Sponsor
Vanderbilt University Medical Center · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
1 May 2017
Primary completion
24 Jun 2021
Completion
24 Jun 2021
First posted
5 Apr 2017
Last update posted
18 Oct 2022
Conditions
Obesity · PreDiabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201720182019202020212022
  1. Ph 4

    Cardiovascular Effects of GLP-1 Receptor Activation

    NCT03101930

    1 May 2017 to 24 Jun 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • LiraglutideDrug
  • SitagliptinDrug
  • hypocaloric dietOther
  • PlacebosDrug
  • Exendin (9-39)Drug

Arms3

  • Experimental

    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.

  • Active comparator

    sitagliptin

    Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks.

  • Active comparator

    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.

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Change in Flow-mediated Dilation

    Time frame · Baseline to 2 and 14 weeks

    Registry description

    Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %)

  2. Urine Albumin-to-creatinine Ratio

    Time frame · Baseline to 13 weeks

    Registry description

    Ratio of urine albumin to creatinine in a spot urine collected after overnight rest

  3. Change in Plasminogen Activator Inhibitor-1

    Time frame · Baseline to 2 and 14 weeks

    Registry description

    Plasma plasminogen activator inhibitor-1 antigen

Secondary outcomes(4)
  1. Blood Pressure

    Time frame · Baseline, and after 2 weeks and 14 weeks of treatment

    Registry description

    The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position

  2. Heart Rate

    Time frame · Baseline, and after 2 weeks and 14 weeks of treatment

    Registry description

    The mean of three measurements with the patient in the supine position

  3. Fasting Glucose

    Time frame · Baseline, and after 2 weeks and 14 weeks of treatment

    Registry description

    Blood glucose collected after overnight fast

  4. Fasting Insulin

    Time frame · Baseline, and after 2 weeks and 14 weeks of treatment

    Registry description

    Plasma insulin collected after overnight fast

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline to 2 and 14 weeks

Change in Flow-mediated Dilation

GroupValue (Percentage)Spread
Liraglutide0.714.82
Sitagliptin2.066.42
Hypocaloric Diet1.245.09
Primary outcomeMean· Baseline to 13 weeks

Urine Albumin-to-creatinine Ratio

GroupValue (mg/g)Spread
Liraglutide12.023.6
Sitagliptin7.97.6
Hypocaloric Diet6.33.8
Primary outcomeMean· Baseline to 2 and 14 weeks

Change in Plasminogen Activator Inhibitor-1

GroupValue (units/mL)Spread
Liraglutide-2.47.8
Sitagliptin-1.38.3
Hypocaloric Diet1.16.9
Secondary and other outcome results(5)
Secondary outcomeMean· Baseline, and after 2 weeks and 14 weeks of treatment

Blood Pressure

GroupValue (mmHg)Spread
Liraglutide124.17.7
Sitagliptin120.211.3
Hypocaloric Diet127.78.3
Secondary outcomeMean· Baseline, and after 2 weeks and 14 weeks of treatment

Heart Rate

GroupValue (Beats per minute)Spread
Liraglutide64.97.5
Sitagliptin67.29.0
Hypocaloric Diet63.88.8
Secondary outcomeMean· Baseline, and after 2 weeks and 14 weeks of treatment

Fasting Glucose

GroupValue (mg/dl)Spread
Liraglutide95.38.6
Sitagliptin97.610.0
Hypocaloric Diet94.512.0
Secondary outcomeMean· Baseline, and after 2 weeks and 14 weeks of treatment

Fasting Insulin

GroupValue (uU/mL)Spread
Liraglutide22.716.8
Sitagliptin23.314.4
Hypocaloric Diet26.721.2
Other pre specified outcomeMean· Change from baseline to 14 weeks

Change in Weight

GroupValue (kg)Spread
Liraglutide-2.723.44
Sitagliptin-0.712.12
Hypocaloric Diet-4.953.98

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
LiraglutideSubjects 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.0 / 460 / 4626 / 46
SitagliptinSubjects 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 / 231 / 236 / 23
Hypocaloric DietSubjects 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 / 241 / 246 / 24

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Men and women, 2. Age 18 to 65 years, and 3. FPG (100-125 mg/dL) or, IGT (two-hour plasma glucose 140-199 mg/dL) or, HbA1C 5.7-6.4% 4. BMI≥30 kg/M2 5. The ability to provide informed consent before any trial-related activities. Exclusion Criteria: 1. Diabetes type 1 or type 2, as defined by a FPG of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication 2. Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control 3. Use of spironolactone 4. Known or suspected allergy to trial medications, excipients, or related products. 5. Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma 6. Personal history of non-familial medullary thyroid carcinoma 7. History of pancreatitis 8. Contraindications to study medications, worded specifically as stated in the product's prescribing information 9. Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control 10. Subjects who have participated in a weight-reduction program during the last six month or whose weight has increased or decreased more than two kg over the preceding six months 11. Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy 12. Treatment with anticoagulants 13. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack 14. History or presence of immunological or hematological disorders 15. Diagnosis of asthma requiring regular inhaler use 16. Clinically significant gastrointestinal impairment that could interfere with drug absorption 17. Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>3.0 x upper limit of normal range) 18. Individuals with an eGFR\<30 mL/min/1.73 m2 or with a UACR \>1000µg/mg, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female) 19. Hematocrit \<35% 20. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult 21. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) 22. Treatment with lithium salts 23. History of alcohol or drug abuse 24. Treatment with any investigational drug in the one month preceding the study 25. Previous randomization in this trial 26. Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study 27. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

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