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A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer
DOI 10.1186/ISRCTN59521990
ClinicalTrials.gov identifier
EudraCT number
Public title A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer
Scientific title
Acronym CAPP2
Serial number at source G0100496
Study hypothesis 1. To study the effect of aspirin and/or resistant starch in a placebo controlled, double-blind randomised trial on carriers of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (Lynch Syndrome);
2. To assess the polyp, adenoma and/or cancer recurrence in these patients during a two to four year treatment period.
Lay summary Not provided at time of registration
Ethics approval Not provided at time of registration
Study design Randomised controlled trial
Countries of recruitment United Kingdom
Disease/condition/study domain Hereditary non-polyposis colorectal cancer (HNPCC)
Participants - inclusion criteria A) Genetic diagnosis:
Proven carriers of pathological mutations in mismatch repair genes

B) Clinical diagnosis:
Belong to a recognised Lynch Syndrome family based on the modified Amsterdam criteria (see below) AND have had at least one of the following events:
1. A colorectal cancer
2. An adenoma of over 5 mm diameter
3. A related carcinoma; endometrial carcinoma is particularly predictive of gene carrier status but others include small bowel, uroepithelial, or stomach
4. An adenoma under 40 years of age
5. Two or more adenomas on more than one occasion
6. Also have had an intact colon or have had only a segmental resection and have normal bowel actions

Modified Amsterdam criteria:
1. Three cases of HNPCC related cancer in the family
2. One is a first degree relative of the other two
3. One under 50 years
4. At least two generations affected

All enrolees should also:
1. Be over 25 years old. There is no upper age limit.
2. Have intact colon or have had only a segmental resection and have normal (non-medicated) bowel actions (three or fewer formed bowel actions per day).
Participants - exclusion criteria 1. Pregnancy (note: there have been few reports of adverse effects associated with aspirin use in pregnancy and aspirin is not regarded as a teratogen so women of child bearing age may be recruited. However, women should temporarily withdraw from the trial if they become pregnant. They can restart immediately after delivery if they are not breast feeding. If mothers are breast feeding they should not re-enter the trial until they have completed breast feeding.)
2. Medical contraindications for aspirin e.g. aspirin induced asthma, previous aspirin/Non-Steroidal Anti-Inflammatory Drug (NSAID) induced peptic ulcer, renal impairment beyond creatinine of 0.15 mmol/l, or haemorrhagic diathesis
3. Already taking NSAIDs or steroids (note: if, during participation in the trial, a participant needs to take a course of NSAIDs they should be temporarily withdrawn from all limbs of the trial)
4. Severe intercurrent disease
5. Known to be Human Immunodeficiency Virus (HIV) positive (routine testing not required)
Anticipated start date 01/01/1999
Anticipated end date 31/01/2008
Status of trial Completed
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 1,000
Interventions Targets Lynch syndrome patients/600 mg enteric coated aspirin daily or placebo AND 30 g resistant starch or placebo:
1. 600 mg aspirin/30 g treatment starch
2. 600 mg placebo tablets/30 g treatment starch
3. 600 mg aspirin/30 g placebo starch
4. 600 mg placebo tablets/30 g placebo starch
Primary outcome measure(s) The primary endpoint will be the number, size and histological stage of colorectal carcinomas found after a minimum of 2 years treatment.
Secondary outcome measure(s) 1. Adenoma size and number:
Elective removal of polyps will make fully developed cancers rare. The main outcome measure will be the number, size, location, villosity and dysplasia of adenomatous polyps
2. Apoptosis in adenomata:
A recent observation in the histology of an adenoma from a participant in CAPP1 has led us to consider that the pattern of apoptosis within adenomata is worthy of study. This is in keeping with the evidence in vivo and in vitro for an effect of aspirin on apoptosis. We will therefore request histopathological assessment of adenomas snared at colonoscopy, with special interest in signet cells and undifferentiated medullary carcinoma.
3. Cell proliferation and apoptosis in flat mucosa:
In a sub-set of participants, biopsies of flat rectal mucosa will be collected before and after treatment to test the hypothesis that altered cell proliferation (see Mills et al. 2001) and/or apoptosis is a reliable biomarker of tumorigenesis.
4. Other cancers:
Gene carriers of Lynch syndrome are at increased risk of many extracolonic cancers, and these will be systematically reported in the study group. In particular, there is a 42% lifetime risk of endometrial cancers in female gene carriers (Dunlop et al., 1997; Watson et al., 1994). These data are important in monitoring any favourable or unfavourable change in all cancers within the different study groups. In particular, it will be important to ascertain if the interventions might reduce colonic tumours while at the same time increasing upper gastrointestinal (GI) or non GI tumours. In mouse studies parallel to CAPP1, we have found a significant increase in small bowel polyps in APC knockout mice fed excess resistant starch (Burn et al., 1996). Aspirin reversed the effect. Regular aspirin use is associated with a reduced incidence of gastric cancer, a malignancy reported with increased frequency in Lynch syndrome families.
Sources of funding Medical Research Council (UK)
Trial website http://www.capp2.com
Publications 1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/19073976
2. 2012 aspirin results in http://www.ncbi.nlm.nih.gov/pubmed/22036019
3. 2012 resistant starch results in http://www.ncbi.nlm.nih.gov/pubmed/23140761
Contact name Prof  John  Burn
  Address CAPP Office
Bioscience Centre
Times Square
Scotswood Road
  City/town Newcastle upon Tyne
  Zip/Postcode NE1 4EP
  Country United Kingdom
  Tel +44 (0)191 2331414
  Fax +44 (0)191 2418680
  Email John.Burn@ncl.ac.uk
Sponsor Newcastle upon Tyne Hospitals NHS Trust (UK)
  Address R&D Department
Royal Victoria Infirmary
Queen Victoria Road
  City/town Newcastle upon Tyne
  Zip/Postcode NE1 4LP
  Country United Kingdom
  Tel +44 (0)191 282 5959
  Fax +44 (0)191 201 0155
  Email craig.mackerness@trvi.nuth.northy.nhs.uk
Date applied 18/05/2001
Last edited 14/11/2012
Date ISRCTN assigned 18/05/2001
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