Thiopurine Induced Pancreatitis in IBD Patients

NCT02281799 | Withdrawn Phase 4

• 1 other identifier: Thiopurine_Pancreatitis
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP) were developed over 50 years ago by Gertrude Elion and George Hitchings and were initially used clinically in the management of childhood leukemia and organ transplantation. The first case report of 6-MP use in inflammatory bowel disease (IBD) was from 1962 , and since then the use of thiopurines has been well established in the management of moderate to severe IBD. Thiopurines offer an inexpensive and effective treatment option for maintenance of remission of IBD in comparison to biological agents which may be 30 times more expensive . Although 50-60% of IBD patients respond to thiopurines, a significant proportion of patients will not tolerate them due to various adverse effects . The adverse effects of thiopurines may be dose related, patient related or idiosyncratic. The immunosuppressive effects of thiopurines also increase the rates of opportunistic infections. Thiopurines are also associated with a higher rate of malignancies, particularly a malignant Burkitt-like lymphoma, related to Epstein-Barr virus infection . Other adverse effects of thiopurine relate to allergic phenomenon. An idiosyncratic adverse effect of thiopurine use is acute pancreatitis (AP). Acute inflammation of the pancreas defined by INSPPIRE criteria: requiring 2 of:

1. 1.Abdominal pain compatible with AP
2. 2.Serum amylase and/or lipase ≥ 3 times upper limits of normal
3. 3.Imaging findings of AP

Conditions

Pancreatitis; Inflammatory Bowel Diseases

Keywords

Azathioprine (AZA); 6-mercaptopurine (6-MP); Thiopurine-S-methyltransferase (TPMT); Xanthine oxidase (XO); 6-thioguanine (6-TGN); 6-methyl-mercaptopurine (6-MMP); inflammatory bowel disease (IBD); acute pancreatitis (AP); inosine triphosphate pyrophosphohydrolase (ITPA); rheumatoid arthritis (RA); systemic lupus erythematosis (SLE); Crohn's disease (CD); ulcerative colitis (UC)

Outcome Measures

Primary Outcomes (1)

• Number of participants demonstrating biochemical or clinical evidence of pancreatitis

  3 month period following intervention

Secondary Outcomes (1)

• Number of participants with adverse events or hospitalization experienced as a result of intervention

  3 month period following intervention

Study Arms (1)

Open label

EXPERIMENTAL

10 patients diagnosed with IBD, treated previously with thiopurines and ceased treatment due to suspected thiopurine-induced pancreatitis. Patients will be commenced on an alternative thiopurine to that used initially,. The medications will be commenced at standard dose (ie Azathioprine 2.5mg/kg/day, 6-MP 1.5mg/kg/day).

Drug: Azathioprine

Interventions

Azathioprine DRUG

Patients will be commenced on an alternative thiopurine to that used initially, according to the standard dosing schedule used by their IBD clinician. For example, if the initial thiopurine-related pancreatitis occurred while taking Azathioprine, the patient will be restarted on 6-MP, and vice versa.

Also known as: 6-mercaptopurine

Open label

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients diagnosed with IBD, treated previously with thiopurines, and ceased treatment due to suspected thiopurine-induced pancreatitis
• Ability to consent to and participate in the study and follow study procedures
• Age 5-60 years

You may not qualify if:

• Previous severe pancreatitis requiring prolonged hospital admission or intensive care involvement, or Ranson's criteria ≥ 3
• No clinical need to reintroduce a thiopurine for management of IBD at the time of the study (e.g. stable on another medication, or mild phenotype of disease), based on clinical assessment of treating gastroenterologist
• Diagnosis of recurrent pancreatitis syndrome
• Diabetes mellitus or any other neuropathy which may dampen the clinical presentation of pancreatitis
• Known or suspected allergy or intolerance to thiopurines, besides previous pancreatitis
• Any other laboratory or clinical condition that the investigator considers clinically significant that could impact the outcome of the study or the safety of the patient.

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead
• Sydney Children's Hospitals Network: collaborator
• Christchurch Hospital: collaborator

Study Sites (1)

Shaare Zedek

Jerusalem, 91031, Israel

Location

MeSH Terms

Conditions

Pancreatitis; Inflammatory Bowel Diseases; Arthritis, Rheumatoid; Crohn Disease; Colitis, Ulcerative

Interventions

Azathioprine; Mercaptopurine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Gastroenteritis; Gastrointestinal Diseases; Intestinal Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds

Study Officials

• Oren Ledder, MD

  Shaare Zedek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: November 4, 2014
• Study Start: March 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: March 18, 2021

Record last verified: 2017-10

Locations

IL (1)