Oxygen deficiency of the human bowel

Phase 1

• Conditions: The participants enrolled in this study will all undergo major upper abdominal surgery (i.e. mostly Pylorus Preserving Pancreatico Duodenectomy or whipple procedure) mostly for pancreatic cancer, papillary carcinoma or pancreatitis. However, the indication for which the IMP is administered is intestinal ischemia and reperfusion.; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2014-002970-36-NL
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-13
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Adult patients (18 years of age and older) undergoing major upper abdominal surgery
oWhipple-procedure or pylorus preserving pancreatico duodenectomy (PPPD)
oIleo-Jejunal bypass surgery
oRoux-en-Y gastric bypass
oTotal gastrectomy
oHepatico jejunostomy
oPancreaticojejunostomy (Frey’s procedure)
?
Patients who have given an informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

Exclusion Criteria

<18 years of age or older but no proper understanding of the research proposal
Inflammatory bowel disease
Celiac disease
Acute major abdominal procedures
Patients who have refused informed consent

For the population who will receive tranexamic acid additional exclusion criteria have been formulated:

Active or history of thrombo-embolic disorders such as deep venous thrombosis, pulmonary embolism or cerebral embolism
History of blood coagulation disorder (hypercoagulation state)
Subarachnoid hemorrhage
Disseminated intravascular coagulation (DIS)
Severe renal insufficiency: i.e. serum kreatinine >150 µmol/L
History of convulsions
Pregnancy
Known hypersensitivity of allergy for tranexamic acid
Simultaneous use of thrombolytics (e.g. alteplase, streptokinase)
Simultaneous use of hormonal anticonceptives or other substances that induce hemostasis.

For the population who will receive doxycycline additional exclusion criteria have been formulated:

Known hypersensitivity of allergy for tetracyclines.
Severe liver function disorder i.e. ASAT or ALAT or AF or ?-GT >150 U/L whether or not combined with severe renal insufficiency: i.e. serum kreatinine >150 µmol/L.
Severe renal insufficiency: i.e. serum kreatinine >150 µmol/L.
Porphyria
Myasthenia gravis
Simultaneous usage (or just before or after administration of doxycycline) of oral retinoids or substances containing metalions (such as antagel or ironpreparations)
Simultaneous use of methoxyflurane (anesthetic) or oral contraceptives
Bodyweight beneath 50 kg
History of blood coagulation disorder (inert hypocoagulation state)
Pregnancy or lactating

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: This study aims at (further) revealing the pathophysiology of intestinal IR in man, with a specific interest for the role of proteases and protease-activated receptor-2 (PAR-2), cellular and inflammatory changes, barrier function and intestinal permeability, microscopic mucosal changes and gene expression patterns. An important element will be the determination of the effects of protease- and MMP inhibitors. By these means we hope to identify preventive and therapeutic strategies for patients with intestinal IR.;Secondary Objective: Not applicable ;Primary end point(s): The primary endpoint in this study is inflammation (neutrophil influx, complement activation, interleukins, TNF-a, COX 1-2) and protease activity in tissue as well as in blood plasma. ;Timepoint(s) of evaluation of this end point: after ischemia, after short respectively prolonged reperfusion and in control samples.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary study parameter is intestinal cell damage, which will be evaluated by assessment of plasma levels of I-FABP, ILBP as well as tissue stainings for morphology, tight junctions, apoptosis, goblet cells, mucines, cell proliferation, I-FABP, L-FABP and SM22. ;Timepoint(s) of evaluation of this end point: after ischemia, after short respectively prolonged reperfusion and in control samples.