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Trial record 14 of 160 for:    GLP-1R

Cardiovascular Effects of GLP-1 Receptor Activation

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ClinicalTrials.gov Identifier: NCT03101930
Recruitment Status : Recruiting
First Posted : April 5, 2017
Last Update Posted : May 9, 2017
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment Phase
Obesity PreDiabetes Drug: Liraglutide Drug: Sitagliptin Other: hypocaloric diet Drug: Placebos Drug: Exendin (9-39) Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Treatment with liragultide or sitagliptin will be masked using matching placebo.
Primary Purpose: Basic Science
Official Title: Cardiovascular Effects of GLP-1 Receptor Activation
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Liraglutide
subcutaneous liraglutide daily

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.

Drug: 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.

Active Comparator: sitagliptin
Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks.
Drug: Sitagliptin
oral sitagliptin daily

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.

Drug: 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.

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.
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.

Drug: 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 Outcome Measures :
  1. flow-mediated dilation [ Time Frame: after one week of treatment ]
    Brachial artery diameter is measured under basal conditions and during reactive hyperemia.

  2. urine albumin-to-creatinine ratio [ Time Frame: after 14 weeks of treatment ]
    ratio of urine albumin to creatinine in a spot urine collected after overnight rest

  3. plasminogen activator inhibitor-1 [ Time Frame: after 14 weeks of treatment ]
    plasma plasminogen activator inhibitor-1 antigen

  4. flow-mediated dilation [ Time Frame: after 14 weeks of treatment ]
    Brachial artery diameter is measured under basal conditions and during reactive hyperemia.


Secondary Outcome Measures :
  1. blood pressure [ Time Frame: after one week and 14 weeks of treatment ]
    The mean of three measurements one minute apart using a oscillometric recording device with patient in supine position

  2. heart rate [ Time Frame: after one week and 14 weeks of treatment ]
    The mean of three measurements with the patient in the supine position

  3. fasting lipids [ Time Frame: after one week and 14 weeks of treatment ]
    Serum triglycerides and free fatty acid collected after overnight fast

  4. fasting glucose [ Time Frame: after one week and 14 weeks of treatment ]
    Blood glucose collected after overnight fast

  5. fasting insulin [ Time Frame: after one week and 14 weeks of treatment ]
    Plasma insulin collected after overnight fas


Other Outcome Measures:
  1. weight [ Time Frame: monthly up to 14 weeks of treatment ]
    weight measured in light clothing without shoes



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03101930


Contacts
Contact: Nancy J. Brown, M.D. 615-343-8701 nancy.j.brown@vanderbilt.edu
Contact: Jessica K Devin, M.D. jessica.k.devin@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Dustin Mayfield, RN    615-343-8701      
Contact: Nancy J Brown, MD    6153438701    nancy.j.brown@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University Medical Center
American Heart Association
Investigators
Principal Investigator: Nancy J. Brown, M.D. Vanderbilt University Medical Center

Responsible Party: Nancy J. Brown, Professor of Medicine and Pharmacology, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03101930     History of Changes
Other Study ID Numbers: IRB# 170213
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action