The Effect of the Adipocyte-derived Hormone Leptin on Endothelial Function in Healthy Men and in Persons With Known Cardiovascular Disease

05-150M

Adipose tissue is an active endocrine organ producing several hormones with circulatory and metabolic effects. In 1994, the hormone leptin was discovered. The lack of this hormone explained extreme obesity in rare patients and parenteral substitution restored body weight and metabolic disturbances. It was however soon discovered that most humans had too high levels which were related to development of cardiovascular diseases and diabetes. It was hypothesised that leptin induced vessel dysfunction which could explain this association. In this study, we wanted to examine the association between leptin and vessel function by using the venous occlusion plethysmography method. We used three protocols to evaluate this association. First protocol. In ten healthy males, leptin was infused locally in the forearm and forearm blood flow (FBF) was measured. Second protocol. In ten healthy males, leptin or normal saline was infused locally in the forearm and FBF was measured. Concomitantly, four vasodilatators were infused locally in the forearm in a randomised order and the response (blood flow and fibrinolysis) was measured. Third protocol. In eighty-three patients with known coronary artery disease, three vasodilators were infused locally in the forearm in a random order and response (FBF and fibrinolysis) was measured. The response was related to endogenous leptin levels. The two first protocols were performed in Umeå, Sweden whereas the third was performed in Edinburgh, UK, all in 2006.

2006-01-01

2006-10-27

2006-12-20

Completed

Early phase I

103

Inclusion criteria protocol 1 and 2; * Healthy male * No regular medication * Non-smoking * Abstain from alcohol for 24 hours and from food, tobacco and caffeine-containing drinks for at least 4 hours before each study visit Inclusion criteria protocol 3; * Established coronary artery disease * Stable angina pectoris * Documented ≥ 50% stenosis of at least one major epicardial coronary vessel Exclusion criteria protocol 3; * Coronary revascularisation within three months * Diabetes mellitus * Cardiac failure (ejection fraction \<35% or New York Heart Association (NYHA) ≥2) * Renal impairment (creatinine ≥200 µmol/L) * Systolic blood pressure \<100 or \>190 mmHg

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'In protocol 1, each participant was examined once. Leptin was given intraarterially in the forearm in increasing doses and forearm blood flow (FBF) was measured. No masking, no randomisation.\n\nIn protocol 2, each participant was examined twice and they got either leptin or saline intraarterially in the forearm at least 2 weeks apart, and the order was randomised. Concomitantly, they got four vasodilatators (bradykinin, acetylcholine, sodium nitroprusside and verapamil) intraarterially in a randomised order.\n\nIn protocol 3, each participant was examined once and the three vasodilatators (substance P, acetylcholine, and sodium nitroprusside) were given intraarterially in the forearm in a randomised order.', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 103, 'type': 'ACTUAL'}}

2023-05-09