Cardiovascular Effects of GLP-1 Receptor Activation

Obesity Clinical Trial

Official title:

Cardiovascular Effects of GLP-1 Receptor Activation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03101930
• Other study ID #: IRB# 170213
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2017
• Est. completion date: June 24, 2021

Study information

• Verified date: September 2022
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: June 24, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• PreDiabetes
• Prediabetic State

Intervention

Drug:
• Liraglutide
subcutaneous liraglutide daily
• Sitagliptin
oral sitagliptin daily

Other:
• hypocaloric diet
Reduced calorie intake to achieve weight loss.

Drug:
• 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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Weight	Weight measured in light clothing without shoes	Change from baseline to 14 weeks
Primary	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
Primary	Urine Albumin-to-creatinine Ratio	Ratio of urine albumin to creatinine in a spot urine collected after overnight rest	Baseline to 13 weeks
Primary	Change in Plasminogen Activator Inhibitor-1	Plasma plasminogen activator inhibitor-1 antigen	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	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	Baseline, and after 2 weeks and 14 weeks of treatment
Secondary	Fasting Glucose	Blood glucose collected after overnight fast	Baseline, and after 2 weeks and 14 weeks of treatment
Secondary	Fasting Insulin	Plasma insulin collected after overnight fast	Baseline, and after 2 weeks and 14 weeks of treatment

External Links

•   Study Pre-print on medRxiv