A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer

ISRCTN	ISRCTN59521990
DOI	https://doi.org/10.1186/ISRCTN59521990
Secondary identifying numbers	G0100496

Submission date: 18/05/2001
Registration date: 18/05/2001
Last edited: 15/06/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Prof John Burn
Scientific

CAPP Office
Bioscience Centre
Times Square
Scotswood Road
Newcastle upon Tyne
NE1 4EP
United Kingdom

Phone	+44 (0)191 2331414
Email	John.Burn@ncl.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer
Study acronym	CAPP2
Study objectives	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.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Hereditary non-polyposis colorectal cancer (HNPCC)
Intervention	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
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Aspirin and resistant starch
Primary outcome measure	The primary endpoint will be the number, size and histological stage of colorectal carcinomas found after a minimum of 2 years treatment.
Secondary outcome measures	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.
Overall study start date	01/01/1999
Completion date	31/01/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	1,000
Total final enrolment	861
Key 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).
Key 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)
Date of first enrolment	01/01/1999
Date of final enrolment	31/01/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

CAPP Office

Newcastle upon Tyne
NE1 4EP
United Kingdom

Sponsor information

Newcastle upon Tyne Hospitals NHS Trust (UK)
Hospital/treatment centre

R&D Department
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom

Phone	+44 (0)191 282 5959
Email	craig.mackerness@trvi.nuth.northy.nhs.uk
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Research council

Medical Research Council (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	11/12/2008		Yes	No
Results article	aspirin results	17/12/2011		Yes	No
Results article	resistant starch results	01/12/2012		Yes	No
Results article	results	13/06/2020	15/06/2020	Yes	No

Editorial Notes

15/06/2020: Publication reference and total final enrolment number added.
17/10/2018: Cancer Research UK lay results summary link added to Results (plain English)