|- candidate number||7907|
|- NTR Number||NTR2274|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||7-apr-2010|
|- Secondary IDs||09/084 METC UMC Utrecht|
|- Public Title||CRC chemoprevention in UC.|
|- Scientific Title||Chemopreventive effects of 5-ASA and UDCA in Ulcerative Colitis: A Double-blind, Randomized Placebo-controlled Pilot Study.
|- ACRONYM||CRC chemoprevention |
|- hypothesis||5-ASA and UDCA have a chemopreventive potential in UC.|
|- Healt Condition(s) or Problem(s) studied||Colorectal cancer, Ulcerative Colitis, Chemoprevention|
|- Inclusion criteria||1. Clinical activity index ¡Ü 4;|
2. Long-standing extensive ulcerative colitis for more than 8 years;
3. Age 18-65 years;
4. Using 6-mercaptopurine or azathioprine to maintain remission;
5. For women only: sufficient anti-conception;
6. Signed informed consent.
|- Exclusion criteria||1. Dysplasia or colorectal cancer before study entry;|
2. Coexistent liver disease (Primary Sclerosing Cholangitis (PSC), chronic hepatitis B or C infection);
4. Family history of colorectal cancer;
5. Symptomatic cholelithiasis;
7. Coagulation disorder or use anticoagulants that can not be temporarily discontinued, precluding the taking of biopsies;
8. Chronic renal impairment/failure;
9. Diabetes mellitus (higher risk for developing renal disease);
10. Hypertension (higher risk for developing renal disease);
11. Allergy to 5-ASA or UDCA;
12. Vertricular/gastric or duodenal ulcera;
14. For women only: Pregnancy, lactation or childbearing potential without adequate contraception;
15. Galactose-intolerance, Lapp lactasedeficience or glucose-galactose malabsorption;
16. Treatment with antacids containing hydroxide, hypolipidemics, high-dose calcium supplements (¡Ý 1200 mg/day), or any other medication disturbing the enterohepatic circulation;
17. Treatment with methotrexate, riphampicine, lactulose or glucocorticosteroids;
18. Unwillingness to be informed about accidental diagnostic findings.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-feb-2010|
|- planned closingdate||1-feb-2013|
|- Target number of participants||45|
|- Interventions||There are three groups:|
1. This group will receive 5-ASA: 4 g a day (4 sachets of 1000mg granu-stix) and UDCA 20-25 mg/kg/day (500mg tablets);
2. This group will receive 5-ASA: 4 g a day (4 sachets of 1000mg granu-stix) and a placebo of UDCA 20-25 mg/kg/day(500mg tablets);
3. This group will receive a placebo of 5-ASA: 4 g a day (4 sachets of 1000mg granu-stix) and a placebo of UDCA 20-25 mg/kg/day (500mg tablets).
Medication will be used during 1 year.
|- Primary outcome||1. Study the chemopreventive potential of 5-ASA and UDCA in UC by evaluating the effect of treatment on ACF number, relative to the placebo group;|
2. Gain mechanistic insight into the chemopreventive properties of 5-ASA and UDCA by genome-wide array based mRNA expression analysis of UC normal colonic mucosa before and after treatment.
|- Secondary outcome||1. Study the chemopreventive potential of 5-ASA and UDCA in UC by evaluating the effect of treatment on ACF size and rate of dysplasia, relative to the placebo group;|
2. Improve understanding of early events in colorectal carcinogenesis by genome-wide array based mRNA expression analysis of dysplastic ACF and UC normal colonic mucosa.
|- Timepoints||1. Baseline: Informed consent, Clinical Activity Index, Bloodsamples, Colonoscopy & staining, Rectal/Sigmoid biopsies NM;|
2. 4 Weeks: Compliance, Adverse effects questionnaire, Bloodsamples;
3. 12 Weeks: Compliance, Adverse effects questionnaire, Bloodsamples;
4. 20 Weeks: Compliance, Adverse effects questionnaire, Bloodsamples;
5. 32 Weeks: Compliance, Adverse effects questionnaire, Bloodsamples;
6. 52 Weeks: Clinical Activity Index, Compliance, Adverse effects questionnaire, Bloodsamples, Colonoscopy & staining, Rectal/sigmoid biopsies NM, Rectal/sigmoid biopsies ACF.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Drs. MD A.M. Leufkens|
|- CONTACT for SCIENTIFIC QUERIES||Drs. MD A.M. Leufkens|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU)|
(Source(s) of Monetary or Material Support)
|Dr Falk Pharma GmbH, Germany|
|- Brief summary||Patients with Ulcerative Colitis (UC), have an increased risk of developing colorectal cancer (CRC). Endoscopic surveillance does not reduce inherent neoplastic potential of the colon and colectomy is associated with medical and psychological complications. The developement of a safe and effective chemopreventive treatment strategy for reducing the overall risk of neoplasia would thus be of substantial benefit to UC patients. Epidemiological case-control studies have indicated that the regular use of 5-aminosalicylic acid (5-ASA) may reduce the risk of developing CRC in UC. Furthermore, 5-ASA and ursodeoxycholic acid (UDCA) has been demonstrated to suppress colitis-associated colon carcinogenesis in mice. Moreover, two retrospective studies have shown that patients with Primary Sclerosing Cholangitis (PSC) and UC had a significantly lower risk of developing dysplasia and CRC than non-treated patients. A recent study in patients with IBD and PSC also suggested that de combined use of 5-ASA and UDCA further decreases the risk of colorectal dysplasia development. Aberrant crypt foci (ACF) are considered to be the earliest identifiable preneoplastic lesions in the multistep proces of colorectal carcinogenesis. Recently, it has been reported that the number of ACF in the rectum increases from patients with UC and no dysplasia, to those with dysplasia and further to UC patients with CRC. Using ACF as a biological end-point rather than the number of colonic tumours has the advantage of a shorter study duration with generation of quantifiable results. Insight into the mechanism of chemopreventive properties of 5-ASA and UDCA has come from studies using CRC cells or animal models of inflammation. We speculate however that identifying the molecular targets in human colonocytes will provide more powerful insight into the mechanisms by which these agents impact neoplastic transformation.|
|- Main changes (audit trail)|
|- RECORD||7-apr-2010 - 22-apr-2010|