Use of Ajunctive Allopurinol in Azathioprine/6-Mercaptopurine Non-responders to Optimize 6-Thioguanine Nucleotide Production and Improve Clinical Outcomes in Patients with Inflammatory Bowel Disease (IBD).

The Triple A (Adjunctive Allopurinol and Azathioprine) Study: Use of Ajunctive Allopurinol in Azathioprine/6-Mercaptopurine Non-responders to Optimize 6-Thioguanine Nucleotide Production and Improve Clinical Outcomes in Patients with Inflammatory Bowel Disease (IBD).

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12611000363987

Acronym

IBDBF1

Enrollment

Registered

2011-04-07

Start date

2011-04-07

Completion date

2014-01-30

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

It is understood that the body metabolizes azathioprine (AZA) to produce two chemical end-products: 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP). 6-TGN is the chemical that makes these drugs work, while 6-MMP causes side-effects. Our research group has previously shown that by adding another drug, allopurinol, patients who otherwise made 6-MMP switched to instead produce 6-TGN, thereby increasing their response to these drugs. Our proposal is for a clinical trial that aims to confirm the safety and efficacy of this clinical maneuver.

Interventions

Eligible IBD patients will be randomly allocated to receive either 100mg or 50mg of allopurinol orally in 1:1 using computer generated list. Patients will continue to take their usual azathioprine or 6-mercaptopurine at reduced doses as determined by the study doctor. The study duration for each individual patient is 24 weeks. Allopurinol will be taken once dail and frequency for usual azathioprine or 6-mercaptopurine treatments remains regular.

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used)

Eligibility

Sex/Gender

All

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

Adult inflammatory bowel disease patients (both Crohn’s disease and ulcerative colitis) taking thiopurine immunomodulators (azathioprine or 6- mercaptopurine) and fulfilling all 3 of the following criteria will be eligible: A) Patient is not in a corticosteroid-free remission. Remission is defined as a Harvey Bradshaw Index (HBI) = 4 for Crohn's Disease (CD) and a Simple Clinical Colitis Activity Index (SCCAI) = 2 for Ulcerative Colitis (UC). B) Patient is metabolizing thiopurines preferentially to produce 6-MMP instead of 6-TGN, with 6-MMP > 5,000 pmol/8 x 108 Red Blood Count (RBC) and 6-TGN < 235 pmol/8 x 108 Red Blood Count (RBC). C) Patient has an adequate initial white blood cell count (WBC) to tolerate the anticipated White Blood Count (WBC) reduction after the addition of allopurinol: White Blood Count(WBC) = 4.5 x109/L. Additionally, patients or their legal guardians must be willing and able to sign the written, informed consent document. (Patients will be eligible for screening as soon as their metabolite profile identifies them to be shunting towards 6-MMP production, meaning a full 12 week trial of thiopurine therapy is not required prior to screening).

Exclusion criteria

1. Suspected or known intolerance or allergy to allopurinol. 2. Concomitant therapy with the following immune modified and biologic agents will not be allowed within the following time intervals from the screening visit: a. Cyclosporine- 4 weeks b. Infliximab- 4 weeks c. Any investigational study drug - 4 weeks. 3. Patients, or legal guardians, unable to give informed consent. 4. Pregnant and breast-feeding patients 5. TPMT heterozygous (TPMTH / TPMTL ) and TPMT homozygous low patients (TPMTL/ TPMTL ).

Outcome results