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The effect of acetylcysteine on thiopurine use related liver injury.


- candidate number5834
- NTR NumberNTR1833
- ISRCTNISRCTN wordt niet meer aangevraagd
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR25-mei-2009
- Secondary IDs2009/56  MEC VUMC
- Public TitleThe effect of acetylcysteine on thiopurine use related liver injury.
- Scientific TitleEffect of N-acetylcysteine on thiopurine related hepatotoxicity in IBD patients.
- ACRONYMNACTOX
- hypothesisThiopurine induced hepatotoxicity is related with an enhanced state of oxidative stress and may ameliorate after N-acetylcysteine supplementation.
- Healt Condition(s) or Problem(s) studiedInflammatory bowel disease, Crohn's disease, Ulcerative Colitis, Hepatotoxicity
- Inclusion criteria1. Crohn's disease and ulcerative colitis;
2. Patients between 18 and 70 years old;
3. Thiopurine use (azathioprine, 6-mercaptopurine or 6-thioguanine) for at least eight consecutive weeks;
4. Grade 1 or 2 toxicity on the CTCAEv3.0 of at least one of the folowing liver tests: ALAT, ASAT, gamma-GT, alkaline phosphatase and bilirubine.
- Exclusion criteria1. Serological findings consistent with auto-immune or viral hepatitis (Hep A,B,C; EBV; CMV);
2. Currently known liver disease;
3. History of chemotherapy;
4. Ultrasonographic findings consistent with cholestasis;
5. Lactation or pregnancy;
6. 6-TGN concentrations above 1200 pmol/8x10*8;
7. Use of antioxidants during thiopurine therapy.
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlNot applicable
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-jun-2009
- planned closingdate1-nov-2010
- Target number of participants30
- InterventionsContinuation of thiopurine treatment during eight weeks. During four weeks 600mg N-acetylcysteine effervescent tablets four times daily.
- Primary outcomeChange in liver tests.
- Secondary outcome1. Change in state of oxidative stress (plasma malondialdehyde, plasma myeloperoxidase, urinary 8-hydroxy- deoxyguanosine and urinary F2-isoprostane);
2. Change in plasma xanthine oxidase activity;
3. Change in amino acid profile.
- TimepointsElligible patients will be screened prior to defenite inclusion. After inclusion they will be randomly assigned to one of the two groups and will visit the outpatient clinics five times with an interval of four weeks. During the first eight weeks thiopurine therapy will be continued and depending on the group patients will concomitantly receive N-acetylcysteine 2400mg daily during weeks 1 to 4 or weeks 5 to 8. Weeks 9 to 12 both thiopurine therapy and N-acetylcysteine will be withdrawn. Rechallenge of solely thiopurine therapy takes place during weeks 13 to 16.
- Trial web siteN/A
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIES D.P. Asseldonk, van
- CONTACT for SCIENTIFIC QUERIES D.P. Asseldonk, van
- Sponsor/Initiator VU University Medical Center
- Funding
(Source(s) of Monetary or Material Support)
VU University Medical Center
- PublicationsN/A
- Brief summaryThioprunes are pivotal in the treatment of inflammatory bowel disease such as Crohn's disease and ulcerative colitis. However, toxicity is a frequent cause of therapy cessation. Hepatotoxicity due to thiopurine therapy may be initiated by an increased state of oxidative stress due to the metabolization of thiopurines on one hand and due to low availability reduced glutathion and its amino acid precursors. By supplementation of N-acetylcysteine we try to reduce oxidative stress and thereby ameliorate hepatotoxicity.
- Main changes (audit trail)
- RECORD25-mei-2009 - 30-sep-2009


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