ObesityTNF4NCT00708266
The Influence of Fatty-Acids on Systemic and Subcutaneous Cytokines
A study testing Openflow microperfusion catheter, Intralipid 20% and 0.9% Saline Solution in people with Obesity and Type 2 Diabetes Mellitus, run by Medical University of Graz at 1 site in Austria.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Obesity, Type 2 Diabetes Mellitus
- What is being tested?
- Openflow microperfusion catheter, Intralipid 20% and 0.9% Saline Solution
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteAustria
- Study dates
- Feb 2007to Apr 2007
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- Any clinical signs of acute or chronic inflammation detectable during study visit 1.
- 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.
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University Graz - Clinical Research Center
Graz, Styria, A-8010
About this study
Official title: A Mono-Centre Randomized Study to Investigate the Effect of Elevated Plasma Fatty Acid Concentrations on Cytokines in Interstitial Fluid of Subcutaneous Adipose Tissue
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.
Read the 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.
- 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) During each study visit subjects shall arrive at 7:00 AM at ZMF (Center of Medical Research, Medical University Graz) after an overnight fasting period of 12 hours. A pregnancy test for female subjects of childbearing potential will be performed in the morning of each study day. Two short polyethylene catheters will be inserted in antecubital veins of both arms. A first venous cannula will be exclusively used for blood sampling and the arm will be placed in a thermo regulated box (Hot-Box) to be maintained warmed at a temperature of 50°C over the whole study period. The second venous cannula will be used for infusion of saline or lipid-heparin solution and inulin. At 8:00 AM, the infusion of saline or Intralipid solution will be started. At the same time point a continuous infusion of inulin via syringe infusion pump will be started with a 50mg/Kg bolus and maintained at a continuous rate of 0.250 x Creatinin Clearance mg/min, until the end of the study period. At 11:00 AM, OFM catheters will be inserted in the periumbilical area of each subject. To prevent important delays in sampling from subcutaneous tissue, the afferent loop for the catheter will be previously filled with the perfusate solution. Eight milliliters of a sterile isotonic solution (ELO MEL isoton, Fresenius Kabi, Austria) commonly used as intravenous infusion added with 2.0ml autologous serum previously withdrawn from each volunteer and prepared under straight sterile conditions will be used as the perfusate solution for the OFM catheters. Peristaltic pumps will start to run at 12:00 AM to infuse the perfusate solutions at a perfusion rate (push-pull mode) of 1µl/min until 12:00 AM in the following day. Effluent samples from subcutaneous tissue will be collected at regular time-intervals and venous blood sampling will be performed in parallel. The subjects will be maintained under fasting conditions during the whole study period. They shall stay in the research center facilities for a four-hours observation period after the study procedures have finished. At this time they will receive a complete meal and additional blood samples will be withdrawn to access blood glucose and aPTT (activated partial tromboplastin time). Normal values have to be ensured before the volunteers are allowed to leave.
- Measurements
3.1. Cytokines
Cytokine concentrations will be measured in effluent and serum samples using a multiplexed flow cytometric bead-based ELISA assay (LUMINEX®100s System, Luminex Corporation, Texas, USA). The following substrates will be accessed by this method:
- C-reactive protein
- Interleukin 6 (IL-6)
- Interleukin 10 (IL-10)
- CCL2/MCP-1
- Serpin E1/PAI-1
- Tumor Necrosis Factor alpha (TNF-alpha)
- Adiponectin
3.2. Insulin
Insulin concentrations in effluent and plasma samples will be measured by Joanneum Research Laboratory using solid-phase two-site ELISA (Mercodia, Uppsala, Sweden).
3.3. Inulin
Inulin will be measured by Joanneum Research Laboratory, using a fully enzymatic method.
3.4. Glucose
Glucose concentration in arterialized blood samples will be measured in duplicate using two Beckman Glucose Analyzer 2 (Beckman Instruments Inc., Fullerton, CA).
3.5. Non-esterified fatty acids (NEFA)
NEFA concentrations will be measured in plasma using a colorimetric and enzymatic method.
- Conditions
- Obesity, Type 2 Diabetes Mellitus
- Being tested
- Openflow microperfusion catheter, Intralipid 20%, 0.9% Saline Solution
- Keywords
- Obesity, Diabetes, Non-esterified fatty acids, Cytokines, Inflammation, Subcutaneous fat, Adipose tissue
- Medical subject headings
- Obesity, Diabetes Mellitus, Type 2, Diabetes Mellitus, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Openflow microperfusion catheterDevice
Also called No other names registered.
Macro-perforated, double lumen catheter used to withdraw interstitial fluid samples from different tissues.
Intralipid 20%Dietary supplement
Also called Liposyn
Lipid emulsion used in clinical practice as supplementary intravenous nutrition. 28 hours venous infusion during the "treatment" study visits.
0.9% Saline SolutionOther
Also called - Saline, - 0.9% Sodium Chloride
0.9% sodium chloride solution, used in clinical practice for venous hydration. 28 hours infusion during the "control" study visits.
| Study group | Role | What they receive |
|---|---|---|
| V2 | Placebo comparator | 28 hours continuous saline venous infusion. Receives: Device: Openflow microperfusion catheter; Other: 0.9% Saline Solution |
| V3 | Experimental | 28 hours continuous lipid-heparin venous infusion. Receives: Device: Openflow microperfusion catheter; Dietary Supplement: Intralipid 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentrations of IL-6 measured in effluent samples from subcutaneous tissue.
Measured: 24 hours of interstitial fluid sampling
Secondary outcomes (2)
Concentrations of all other cytokines measured in effluent samples from subcutaneous tissue.
Measured: 24 hours of interstitial fluid sampling.
Cytokine concentrations measured in serum samples.
Measured: 24 hours sampling during the experiment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2008 (estimated)
- Study startFeb 2007
- Primary completionApr 2007
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Medical University of GrazThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Investigators
- Thomas R. Pieber, M.D., Principal investigator, Medical University Graz, Graz, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00708266
- Sponsor's protocol ID
- TNF4
- Acronym
- TNF4
- Status last verified
- Jun 2008
- First submitted
- 27 Jun 2008
- Last updated
- 2 Jul 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Mono-Centre Randomized Study to Investigate the Effect of Elevated Plasma Fatty Acid Concentrations on Cytokines in Interstitial Fluid of Subcutaneous Adipose Tissue
- ClinicalTrials.gov ID
- NCT00708266
- Acronym / sponsor ID
- TNF4 / TNF4
- Conditions
- Obesity, Type 2 Diabetes Mellitus
- Keywords
- Obesity, Diabetes, Non-esterified fatty acids, Cytokines, Inflammation, Subcutaneous fat, Adipose tissue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- Feb 2007
- Primary completion
- Apr 2007 (actual)
- Study completion
- Apr 2007 (actual)
- First posted
- 2 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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) During each study visit subjects shall arrive at 7:00 AM at ZMF (Center of Medical Research, Medical University Graz) after an overnight fasting period of 12 hours. A pregnancy test for female subjects of childbearing potential will be performed in the morning of each study day. Two short polyethylene catheters will be inserted in antecubital veins of both arms. A first venous cannula will be exclusively used for blood sampling and the arm will be placed in a thermo regulated box (Hot-Box) to be maintained warmed at a temperature of 50°C over the whole study period. The second venous cannula will be used for infusion of saline or lipid-heparin solution and inulin. At 8:00 AM, the infusion of saline or Intralipid solution will be started. At the same time point a continuous infusion of inulin via syringe infusion pump will be started with a 50mg/Kg bolus and maintained at a continuous rate of 0.250 x Creatinin Clearance mg/min, until the end of the study period. At 11:00 AM, OFM catheters will be inserted in the periumbilical area of each subject. To prevent important delays in sampling from subcutaneous tissue, the afferent loop for the catheter will be previously filled with the perfusate solution. Eight milliliters of a sterile isotonic solution (ELO MEL isoton, Fresenius Kabi, Austria) commonly used as intravenous infusion added with 2.0ml autologous serum previously withdrawn from each volunteer and prepared under straight sterile conditions will be used as the perfusate solution for the OFM catheters. Peristaltic pumps will start to run at 12:00 AM to infuse the perfusate solutions at a perfusion rate (push-pull mode) of 1µl/min until 12:00 AM in the following day. Effluent samples from subcutaneous tissue will be collected at regular time-intervals and venous blood sampling will be performed in parallel. The subjects will be maintained under fasting conditions during the whole study period. They shall stay in the research center facilities for a four-hours observation period after the study procedures have finished. At this time they will receive a complete meal and additional blood samples will be withdrawn to access blood glucose and aPTT (activated partial tromboplastin time). Normal values have to be ensured before the volunteers are allowed to leave.
- Measurements
3.1. Cytokines
Cytokine concentrations will be measured in effluent and serum samples using a multiplexed flow cytometric bead-based ELISA assay (LUMINEX®100s System, Luminex Corporation, Texas, USA). The following substrates will be accessed by this method:
- C-reactive protein
- Interleukin 6 (IL-6)
- Interleukin 10 (IL-10)
- CCL2/MCP-1
- Serpin E1/PAI-1
- Tumor Necrosis Factor alpha (TNF-alpha)
- Adiponectin
3.2. Insulin
Insulin concentrations in effluent and plasma samples will be measured by Joanneum Research Laboratory using solid-phase two-site ELISA (Mercodia, Uppsala, Sweden).
3.3. Inulin
Inulin will be measured by Joanneum Research Laboratory, using a fully enzymatic method.
3.4. Glucose
Glucose concentration in arterialized blood samples will be measured in duplicate using two Beckman Glucose Analyzer 2 (Beckman Instruments Inc., Fullerton, CA).
3.5. Non-esterified fatty acids (NEFA)
NEFA concentrations will be measured in plasma using a colorimetric and enzymatic method.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| V2 | Placebo comparator | Device: Openflow microperfusion catheter, Other: 0.9% Saline Solution28 hours continuous saline venous infusion. |
| V3 | Experimental | Device: Openflow microperfusion catheter, Dietary Supplement: Intralipid 20%28 hours continuous lipid-heparin venous infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (6 listed)
- Any clinical signs of acute or chronic inflammation detectable during study visit 1.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Openflow microperfusion catheterAlso: No other names registered.Macro-perforated, double lumen catheter used to withdraw interstitial fluid samples from different tissues. | Device | V2, V3 |
| Intralipid 20%Also: LiposynLipid emulsion used in clinical practice as supplementary intravenous nutrition. 28 hours venous infusion during the "treatment" study visits. | Dietary supplement | V3 |
| 0.9% Saline SolutionAlso: - Saline, - 0.9% Sodium Chloride0.9% sodium chloride solution, used in clinical practice for venous hydration. 28 hours infusion during the "control" study visits. | Other | V2 |
Primary outcome
Concentrations of IL-6 measured in effluent samples from subcutaneous tissue.
Time frame: 24 hours of interstitial fluid sampling
2 secondary outcomes
Concentrations of all other cytokines measured in effluent samples from subcutaneous tissue.
Time frame: 24 hours of interstitial fluid sampling.
Cytokine concentrations measured in serum samples.
Time frame: 24 hours sampling during the experiment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas R. Pieber, M.D. principal investigator
Medical University Graz, Graz, Austria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Openflow microperfusion catheter, Intralipid 20% and 0.9% Saline Solution in people with Obesity and Type 2 Diabetes Mellitus, run by Medical University of Graz at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentrations of IL-6 measured in effluent samples from subcutaneous tissue. (time frame: 24 hours of interstitial fluid sampling). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2008.