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ID
Source
Brief title
Health condition
Inflammatory bowel disease; IBD; Crohn's disease; de ziekte van Crohn; ulcerative colitis; colitis ulcerosa; thiopurines; oxidative stress; hepatotoxicity; levertestafwijkingen
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in liver tests.
Secondary outcome
1. 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.
Background summary
Thioprunes 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.
Study objective
Thiopurine induced hepatotoxicity is related with an enhanced state of oxidative stress and may ameliorate after N-acetylcysteine supplementation.
Study design
Elligible 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 Weeks 9 to 12 both thiopurine therapy and N-acetylcysteine will be withdrawn.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.
Intervention
Continuation of thiopurine treatment during eight weeks. During four weeks 600mg N-acetylcysteine effervescent tablets four times daily.
VU University Medical Center,
De boelelaan 1118
Amsterdam 1081 HV
The Netherlands
+31 (0)20 4440613
d.vanasseldonk@vumc.nl
VU University Medical Center,
De boelelaan 1118
Amsterdam 1081 HV
The Netherlands
+31 (0)20 4440613
d.vanasseldonk@vumc.nl
Inclusion criteria
1. 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 criteria
1. 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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL1723 |
| NTR-old | NTR1833 |
| Other | MEC VUMC : 2009/56 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd |