Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults

NCT02333591 | Completed Phase 4 DMC

• 2 other identifiers: MZ022013-001240-64
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the cardiovascular system. The mechanism is complex and there seems to be a dual function with intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1 receptor. Coronary flow reserve (CFR) is the ratio of flow through the coronary arteries during stress to during rest and it reflects coronary microcirculation. Impaired CFR is a strong predictor of poor prognosis of cardiovascular disease. The aim of the study is to investigate the acute effects of GLP-1 on coronary microcirculation and endothelial function in adults with obesity.

Conditions

Coronary Microvascular Dysfunction

Outcome Measures

Primary Outcomes (1)

• Coronary Flow Reserve

  Coronary flow reserve (CFR) reflects microvessel coronary function and is the ratio between echocardiographic measured coronary flow velocity in LAD during adenosine induced myocardial hyperaemia and rest. The outcome is measured at every infusion/intervention (4 times).

  At baseline and after 2 hours of infusion

Secondary Outcomes (1)

• Endothelial function (Assessed by Flow Mediated Dilation)

  At baseline and after 1 hour of infusion

Study Arms (3)

GlucagonLikePeptide-1 (7-36)

ACTIVE COMPARATOR

GLP-1 (7-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (7-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min. A DPP-IV inhibitor - Januvia 100 mg is given the evening before and ½ an hour before the infusion is started.

Drug: Saline

GlucagonLikePeptide-1 (9-36)

ACTIVE COMPARATOR

GLP-1 (9-36) is diluted in saline and human serum albumin. Plasma levels of GLP-1 (9-36) are rapidly raised and then maintained stable with 5,91 pmol/kg/min (0-2 min) reduced to 2,53 pmol/kg/min (2-4 min) reduced to 2,34 pmol/kg/min (4-6 min) reduced to 2,2 pmol/kg/min (6-8 min) reduced to 2,02 pmol/kg/min (8-10 min) and then maintained stable for 2½ hours with 1.5 pmol/kg/min

Drug: Saline

NaCl

PLACEBO COMPARATOR

Saline is infused with a flow rate of 240 ml/h for 10 min and then reduced to 86 ml/h for 2½ hours.

Drug: GlucagonLikePeptide-1 (7-36); Drug: GlucagonLikePeptide-1 (9-36)

Interventions

GlucagonLikePeptide-1 (7-36) DRUG

Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.

NaCl

GlucagonLikePeptide-1 (9-36) DRUG

Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.

NaCl

Saline DRUG

Infused intravenously for 2,5 hours.

Also known as: NaCl, Placebo

GlucagonLikePeptide-1 (7-36); GlucagonLikePeptide-1 (9-36)

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 35-70 years
• BMI \> 25 kg/m2.
• Central obesity (measured by waist circumference, defined as ≥ 94cm for men and ≥ 80 cm for women)
• Non smokers (6 months abstinent is required)
• Normal creatinine
• For fertile women; negative pregnancy test and use of safe anticonception.
• Speak and understand Danish or English
• Mental ability to follow and understand the study

You may not qualify if:

• Known Diabetes
• Haemoglobin \< 6.5 mmol/l
• Allergy towards Januvia or Exenatide, Adenosin or Glycerylnitrate
• Documented significant stenosis of the left anterior descending artery (LAD) at coronary angiography or CT-angiography or regional dysfunction documented during dipyridamol stress-echocardiography. If stress test at baseline shows significant stenosis the patient will be excluded from the study.
• Pregnancy
• Severe asthma
• Active cancer, severe co-morbidity with limited life-expectancy, severe hepatic co-morbidity, chronic alcohol abuse, atrial fibrillation, chronic or previous acute pancreatitis, inflammatory bowel disease.

Sponsors & Collaborators

• Mette Zander: lead
• Hvidovre University Hospital: collaborator

Study Sites (1)

Department of Research in Endocrinology, Bispebjerg University Hospital

Copenhagen, 2400, Denmark

Location

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Mette Zander, PhD, MD

  Department of Endocrinology, Bispebjerg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 7, 2015
• Study Start: July 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: March 11, 2019

Record last verified: 2019-03

Locations

DK (1)