Leptin Infusion and Endothelial Vasomotor Response

Summary

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.

Conditions

• Endothelial Dysfunction
• Obesity
• Vasodilation
• Venous Occlusion Plethysmography

Interventions

DRUG

Leptin infusion plus vasodilators in healthy men

This applies only to protocol 2 with two arms (leptin or saline) where four vasodilatators (bradykinin, acetylcholine, sodium nitroprusside and verapamil) were infused concomitantly

DRUG

Leptin infusion in healthy men

This applies only to protocol 1 when only leptin was given

DRUG

Vasodilators in CAD patients

This applies only to protocol 3

Sponsors & Collaborators

• University of Edinburgh

  collaborator OTHER

• Stefan Soderberg

  lead OTHER

Principal Investigators

• Stefan Söderberg, MD, PhD · Umeå University, Umeå Sweden

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2006-01-01

Primary Completion

2006-10-27

Completion

2006-12-20

FDA Drug

Yes

Countries

• Sweden
• United Kingdom

Study Locations