Clinical trial NCT03101930: Cardiovascular Effects of GLP-1 Receptor Activation
Official title: Cardiovascular Effects of GLP-1 Receptor Activation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
PreDiabetes
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2017-04-05
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Flow-mediated Dilation
timeFrame: Baseline to 2 and 14 weeks
measure: Urine Albumin-to-creatinine Ratio
timeFrame: Baseline to 13 weeks
measure: Change in Plasminogen Activator Inhibitor-1
timeFrame: Baseline to 2 and 14 weeks
Secondary outcomes:
measure: Blood Pressure
timeFrame: Baseline, and after 2 weeks and 14 weeks of treatment
measure: Heart Rate
timeFrame: Baseline, and after 2 weeks and 14 weeks of treatment
measure: Fasting Glucose
timeFrame: Baseline, and after 2 weeks and 14 weeks of treatment
measure: Fasting Insulin
timeFrame: Baseline, and after 2 weeks and 14 weeks of treatment
Other outcomes:
measure: Change in Weight
timeFrame: Change from baseline to 14 weeks
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: James M. Luther, M.D.
role: PRINCIPAL_INVESTIGATOR
References: