Does mitogen activated protein kinase inhibition with CNI-1493 prevent post-Endoscopic retrograde cholangiopancreatography pancreatitis?

ISRCTN ISRCTN26235881
DOI https://doi.org/10.1186/ISRCTN26235881
Secondary identifying numbers N/A
Submission date
20/12/2005
Registration date
20/12/2005
Last edited
20/08/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr M J Bruno
Scientific

Academical Medical Centre
Department of Gastroenterology-Hepatology (MDL)
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Email m.j.bruno@amc.uva.nl

Study information

Study designRandomised, placebo controlled, parallel group, double blinded trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleDoes mitogen activated protein kinase inhibition with CNI-1493 prevent post-Endoscopic retrograde cholangiopancreatography pancreatitis?
Study acronymCNI study
Study objectivesAcute pancreatitis can be due to many causes including biliary stone disease, alcohol abuse, and medication. It can also be caused by medical intervention through manipulation of area of the ampulla of Vater and diagnostic and/or therapeutic interventions in the biliary and pancreatic ductal system (endoscopic retrograde cholangiopancreaticography [ERCP]).

The overall reported incidence of post-ERCP pancreatitis is 7%, in certain subgroups with an increased risk this goes up to 20%. Local damage (temporary increased ductal pressure due to contrast injection and/or oedema due to manipulations) is followed by a local inflammatory response (Tumour Necrotising Factor [TNF], Interleukin-one [IL-1], Interleukin-six [IL-6]). In 80% of cases post-ERCP pancreatitis runs a relatively benign course with a few day of (severe) abdominal pain and an uneventful recovery. In other cases a severe pancreatitis develops with necrosis of parenchymal pancreatitis tissue (with or without infection) and a Systemic Inflammatory Response Syndrome (SIRS).

In the latter group morbidity and mortality are high. Of these patients 25% will die. Recently, a group of synthetic guanylhydrazone compounds have been developed and one of its representatives CNI-1493 (a p38 Mitogen Activated Protein [MAP] kinase inhibitor) proved to be a very powerful inhibitor of TNF-alpha. In addition, CNI-1493 inhibits a host of other macrophage induced pro-inflammatory cytokines (IL-1, IL-6, MIP-1ƒÑ and MIP-1ƒÒ).

The primary question that we want to address is whether it is possible with the prophylactic administration of CNI-1493 to lower the incidence of post-ERCP pancreatitis.

Hypothesis:
Prophylactic administration of p38 MAP/c-Jun N-terminal protein Kinase (JNK) inhibitor may decrease the incidence of post-ERCP pancreatitis through inhibition of the pro-inflammatory cytokines IL-1, IL-6, TNF and Macrophage Inflammatory Protein (MIP). In animal studies CNI-1493 or related compounds have been shown to reduce the severity of experimental pancreatitis and pancreatitis associated lung injury.
Ethics approval(s)Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studiedEndoscopic Retrograde Cholangiopancreatography (ERCP), pancreatitis
InterventionSingle infusion of CNI-1493 (50 mg intravenous [IV] or placebo IV (randomised, double blind) one hour prior to start of ERCP.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)CNI-1493
Primary outcome measureDoes administration of CNI-1493 decrease the incidence of post ERCP pancreatitis in high risk patients undergoing ERCP?
Secondary outcome measures1. Is CNI-1493 administration safe in patients undergoing ERCP?
2. Does administration of CNI-1493 decrease the severity of post ERCP pancreatitis in high risk patients undergoing ERCP?
3. Does administration of CNI-1493 decrease the incidence of post ERCP hyperamylasemia in high risk patients undergoing ERCP?
4. Does administration of CNI-1493 decrease the levels of post ERCP IL-6, Interleukin-eight (IL-8), TNF and IL-1 in high risk patients undergoing ERCP?
Overall study start date01/03/2002
Completion date31/12/2005

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexNot Specified
Target number of participants270
Key inclusion criteria1. Included are all patients who do not fit the exclusion criteria and will undergo an ERCP with the intention to:
a. cannulate and visualise the pancreatic duct
b. perform therapeutic procedures (e.g. stenting, balloon dilatation, sphincter manometry, precut papillotomy, stone extraction, (intra-luminal) endosonography, Extracorporeal Shock-Wave Lithotripsy [ESWL] and dilatation) in the pancreatic duct, common bile duct or left and right hepatic ducts
2. Patients must agree to use acceptable means of birth control for at least three months after the procedure
3. Patients must sign informed consent
Key exclusion criteria1. Diagnostic ERCP (low risk)
2. Active pancreatitis at time of ERCP (confounding)
3. Severe abdominal pain pre ERCP (confounding)
4. Age less than 18 years (contra-indication)
5. Known or suspected pregnancy or breast-feeding (contra-indication)
6. ERCP for stent exchange in malignant disease (low risk)
7. Severe chronic pancreatitis (low risk)
8. Kidney failure i.e. serum creatinine greater than 20 mg/dl (greater than 180 µM) (any state, contra-indication)
9. Other anti-TNF therapy (e.g. infliximab) within eight weeks of intended study treatment
Date of first enrolment01/03/2002
Date of final enrolment31/12/2005

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Academical Medical Centre
Amsterdam
1105 AZ
Netherlands

Sponsor information

Cytokine PharmaSciences, Inc (USA)
Industry

Walnut Hill Plaza
150 South Warner Road
Suite 420
King of Prussia
PA 19406
United States of America

Website http://www.cytokinepharmasciences.com/
ROR logo "ROR" https://ror.org/02ytn5d60

Funders

Funder type

Industry

Cytokine PharmaSciences, Inc (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Editorial Notes

20/08/2021: Proactive update review. No publications found. Search options exhausted.