A Mono-Centre Randomized Study to Investigate the Effect of Elevated Plasma Fatty Acid Concentrations on Cytokines in Interstitial Fluid of Subcutaneous Adipose Tissue
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Concentrations of IL-6 measured in effluent samples from subcutaneous tissue.
Study Overview
Brief Summary
This is a mono-center randomized controlled trial to be performed in the Center of Medical Research (ZMF) at Medical University Graz and is composed by one screening visit (V1) and two study visits (V2 and V3). In the visit V1, complete medical examination will be performed and blood samples will be withdrawn to check overall conditions of the healthy volunteers. Those who accomplish the necessary conditions will be enrolled in the trial to receive either saline or lipid-heparin solutions in a randomized, cross-over design during visits V2 and V3. Volunteers will arrive at ZMF after overnight fasting, when two venous catheters will be placed in forearm veins. One venous catheter will be used for continuous infusion of lipid-heparin solution (Intralipid 20%, 40 ml/h, Fresenius Kabi plus Heparin 250U/h, IMMUNO Baxter AG) or saline, and Inulin (Inutest 25%, Fresenius Kabi). The second venous catheter will be used for blood sampling (arterialized venous blood). Subsequently, two open flow microperfusion (OFM) macro-perforated catheters will be inserted in the subcutaneous tissue of abdominal wall for continuous sampling of interstitial fluid. Study visits will last for 28 hours for continuous sampling, with four additional hours for observation after infusion discontinuation, during visits V2 and V3. Concentrations of different cytokines, non-esterified fatty-acids, insulin, glucose, triglycerides and inulin will be retrospectively quantified in the frozen samples.
The primary hypothesis is that cytokine concentrations in subcutaneous tissue and/or in circulation can be modified by lipid-heparin infusion.
Detailed Description
- General
Subjects will be selected to participate in the protocol during study visit 1 according to the inclusion and exclusion criteria. Subsequently they will be randomly assigned to receive continuously an intravenous infusion of 0.9% saline or a lipid-heparin solution (Intralipid 20%, 40 ml/h, Fresenius Kabi plus Heparin 250U/h, IMMUNO Baxter AG) during 28 hours at study visits V2 and V3. For the study visit 3, subjects who first received 0.9% saline in the previous visit, will receive intravenously Intralipid 20% and vice versa. 2. Visit Procedures
2.1. Screening Day (Visit 1)
Volunteers will receive overall information about the study and sign in the written informed consent. Every subject will receive an assignment number according to the inclusion sequence. Physical examination and blood withdrawal shall be performed and data will be recorded in the Case Report Form (CRF) as follows:
- Inclusion/exclusion criteria
- Demographic data, medical history and concomitant medication
- Physical examination
- Vital signs
- Body weight and height, Body mass index (BMI), waist and hip circumference and waist-to-hip ratio
- Blood blood count, hematocrit, hemoglobin, C-reactive protein, free fatty acids, cholesterol, triglycerides, sodium, potassium, calcium
- Pregnancy test for female subjects of childbearing potential.
2.2. Study day (Visit 2 and 3)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Informed consent signed before any study activities.
- •Age of 18 years old or above.
- •A body mass index (BMI) within the limits of 18.5 to 24.9 (normal range).
Exclusion Criteria
- •Any clinical signs of acute or chronic inflammation detectable during study visit
- •Severe acute or chronic diseases (e.g. acute respiratory tract infection, systemic lupus erythematosus, rheumatoid arthritis).
- •Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
- •Use of any vasoactive substances (e.g. anti-hypertensive drugs), immune-suppressant or anti-inflammatory drugs (e.g. corticosteroids, aspirin, other COX2 inhibitors) or anti-coagulation treatment.
- •Diseases of the skin which could interfere with catheter insertion in the abdominal wall.
- •Pregnancy in women subjects.
Outcomes
Primary Outcomes
Concentrations of IL-6 measured in effluent samples from subcutaneous tissue.
Time Frame: 24 hours of interstitial fluid sampling
Secondary Outcomes
- Concentrations of all other cytokines measured in effluent samples from subcutaneous tissue.(24 hours of interstitial fluid sampling.)
- Cytokine concentrations measured in serum samples.(24 hours sampling during the experiment)