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Trial registered on ANZCTR


Registration number
ACTRN12613000097741
Ethics application status
Approved
Date submitted
8/11/2012
Date registered
25/01/2013
Date last updated
14/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination of Selenium and Green Tea on bowel health
Scientific title
Effects of combining Selenium (Se) and green tea on biomarkers for colorectal cancer prevention in human subjects
Secondary ID [1] 281111 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bowel Cancer 287271 0
Condition category
Condition code
Cancer 287596 287596 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
30 healthy volunteers (>50yrs) at-risk for CRC by virtue of age and /or other standard risk factors will be recruited to participate in a randomised, three cohort dietary intervention study. with a parallel design to test the effects of Se and green tea alone and in combination on molecular biomarkers for CRC prevention in the normal rectal epithelial cells. They will be instructed to maintain their usual diet during the study but to avoid supplementation with any green tea-related food or drink (limited to <3 cups of black tea per day), and Se-rich foods such as octopus, crab and tuna, liver and kidney or additional Brazil nuts or other nuts (except those Brazil nuts and green tea extract prescribed by us). The study will consist of dietary intervention period of 6 weeks, preceded by a run in period of 4 weeks.

The volunteers will be randomised (randomisation will be computer generated) into one of three groups of 10, receiving
1) Se, supplied as Brazil nuts (6 Brazil nuts daily will provide 48micrograms Se/day);
2) Green tea, supplied as a green tea extract capsule (4 capsules daily will provide 800mg EGCG/day); and
3) Se + green tea (6 Brazil nuts daily + 4 green tea extract capsules daily (will provide 48micrograms Se/day and 800mg EGCG/day).

Six Brazil nuts has been chosen because the average Se concentration (2.7 micrograms Se/g) in Brazil nuts (supplied from Charlesworth, Australia) is relatively low compared to that of the report by Thomson et al, where the Se concentration is 6.4micrograms Se/g, and average weight for one nut is 4g, 2 nuts provided 53 micrograms Se/day (Am J Clin Nutr 2008;87:379-3840). Since the average weight of one Brazil nut (supplied from Charlesworth, Australia) is 3g, 6 Brazil nuts daily will provide 48micrograms Se/day, similar to the dose of 53micrograms Se/day.

The green tea dose depends on the concentration of epigallocatechin-3-gallate (EGCG) per capsule, one green tea extract capsule containing 200mg of EGCG is supplied by NOW Foods, USA, 4 capsules of green tea has been chosen because it is equivelant to 4-6 cups of green tea, which could be achieved in humans. Intake of a green tea extract capsule containing 400mg EGCG up to 2,000mg EGCG is safe in human trials (J Clin Oncol. 2009 Aug 10;27(23):3808-14). The intervention period is 6 weeks to replicate the intervention period of our previous Se human trial (Br J Nutr. 2011 Aug;106(4):572-582). Also 6 weeks is the time when maximum plasma Se level was achieved after supplementation of 2 Brazil nuts in a clinical human trial, where 2 Brazil nuts daily was shown to be as effective for increasing Se status as 100micrograms selenomethionine (Am J Clin Nutr 2008;87:379-3840). Our previous studies and others have also shown that 4-6 weeks of dietary intervention proved to be suitable to reveal changes in biomarkers in rectal biopsies (Br J Nutr 2007;98:525-534).

Immediately prior to the allocated dietary intervention and subsequently after 6 weeks of dietary intervention, blood samples will be collected and rectal biopsies (four biopsies are taken during each procedure) will be taken by sigmoidoscopic examination performed without bowel preparation. The biopsies will be performed by an experienced proceduralist who has performed these procedures previously. An initial 4 week pre-treatment assessment period will precede the supplementation. The first blood sample will be taken at the start of this period and it will be assayed for Se to determine if the entry criterion for plasma Se is met.
The Brazil nut is a large nut that comes from the castanheiro de para tree in Brazil's rainforests. Each serving of about six to eight nuts contains 4 g of protein and 7 grams each of monosaturated and polysaturated fat.
Brazil nuts (Berholletia excelas, family Lecythidaceae) are the richest known food source of selenium, with mean concentrations reported in the literature between 8-83 micrograms Se/g
Intervention code [1] 285565 0
Prevention
Comparator / control treatment
The study will consist of dietary intervention period of 6 weeks, preceded by a run in period of 4 weeks.
The volunteers will be randomised (this will be computer generated) into one of three groups of 10, receiving
1) Se, supplied as Brazil nuts (6 Brazil nuts daily will provide 48micrograms Se/day);
2) Green tea, supplied as a green tea extract capsule (4 capsules daily will provide 800mg EGCG/day); and
3) Se + green tea (6 Brazil nuts daily + 4 green tea extract capsules daily (will provide 48micrograms Se/day and 800mg EGCG/day).
The treatment comparator will not only compare to each group but also compare within each individual, i.e. before and after the treatment
Control group
Active

Outcomes
Primary outcome [1] 287858 0
Effects of combination diet (Se + green tea) on biomarkers of Wnt pathway (catenin), inflammation (COX-2) and DNA repair (MGMT) in rectal epithelium. Rectal biopsies will be collected and examined by RT-PCR and immunohistochemistry for the expression of these biomarkers at gene and protein levels
Timepoint [1] 287858 0
Commencement of Intervention (Baseline),
End of intervention (6 weeks)
Secondary outcome [1] 298949 0
1. Effect of combination diet (Se + green tea) on plasma Se and EGCG levels.
We expect the combination diet will increase plasma Se and EGCG levels, increase Se levels is associated with reduced cancer risk, whereas EGCG is an bioactive compound found in green tea, that has anticancer activity. The interaction between Se and green tea might increase the bioavailability and biological activity of both Se and EGCG
Timepoint [1] 298949 0
Commencement of Intervention (Baseline),
End of intervention (6 weeks)
Secondary outcome [2] 300741 0
2. Effect of combination diet (Se + green tea) on rectal selenoprotein expression (SeP, GPx-1, GPx-2mRNA).
DNA from the rectal biopsies will be extracted, transformed to cDNA, PCR will be conducted to measure these selenoprotein gene.
Timepoint [2] 300741 0
Baseline (commencement of Intervention)
After 6 weeks of Intervention

Eligibility
Key inclusion criteria
Participants will be age >50 years & <75yrs
Healthy, with no active bowel disease (previous history of adenoma removal >6 months ago is allowable)
Plasma Se at or below 106 microgram/dL (to ensure that people with a high background Se status for whatever reason are not included in the study)
Potential participants will be offered a faecal immunochemical test kit ( an β€œFIT”, the latest technology FOBT) to screen for the possibility for CRC. If positive, we would assist them to get follow-up and they would not be eligible for the study while this was being clarified.
Minimum age
50 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Evidence of any active mucosal bowel disease, eg colitis, or of malabsorption
Previous bowel surgery (excluding polypectomy)
Previous colorectal cancer, or previous adenoma not removed or adenoma removed within last 6 moinths
Any allergy or intolerance to nuts or green tea products
Unwilling to record Se or green tea intake
Prescribed & taking warfarin or antiplatelet agents (such as asprin) precluding safe biopsy
If less than 85% of Brazil nuts and green tea capsules are consumed the participant will be deemed non compliant.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be recurited by advertisement and/or will be identified from clinic records as having had a previous bowel examination. They will be approached by a study doctor or associated research nurse, and may possibly be invited to an information session
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
nil
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 447 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 6208 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 285893 0
Government body
Name [1] 285893 0
National Health and Medical Research Council
Address [1] 285893 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
GPO Box 1421
Canberra ACT 2601
Country [1] 285893 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
1 Flinders Drive
Bedford Park
5042
South Australia
Country
Australia
Secondary sponsor category [1] 284716 0
None
Name [1] 284716 0
Address [1] 284716 0
Country [1] 284716 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288016 0
Southern Adelaide Clinical Human Research Ethics Committee.
Ethics committee address [1] 288016 0
Flinders Medical Centre,
Flinders Drive
Bedford Park
SA 5042
Ethics committee country [1] 288016 0
Australia
Date submitted for ethics approval [1] 288016 0
19/07/2012
Approval date [1] 288016 0
05/10/2012
Ethics approval number [1] 288016 0
1/12/0308

Summary
Brief summary
This study will evaluate whether combination dietary supplementation of selenium and green tea can reduce the risk of developing bowel cancer in healthy humans. Who is it for? You may be eligible to join this study if you are a healthy man or woman aged between 50-75 years, with no active bowel disease. You should have no previous colorectal cancer and no allergy or intolerance to nuts or green tea products. Trial details Participants will be randomly (by chance) divided into three groups. Participants in one group will eat 6 brazil nuts per day (providing 48mcg selenium/day). Participants in the second group will take 4 green tea extract capsules daily. A third group will take both of these in combination. All dietary interventions are continued for 6 weeks. Participants will be required to give blood samples and rectal biopsies before and after treatment (at 6 weeks) in order to assess response to the different dietary interventions. This study will provide valuable information on how a combinational dietary approach may reduce the risk of developing colorectal (bowel) cancer in humans.
Trial website
Trial related presentations / publications
not yet available
Public notes

Contacts
Principal investigator
Name 34630 0
Prof Graeme P Young
Address 34630 0
Professor of Global GI Health
Department of Gastroenterology
Flinders University
Bedford Park
SA 5042
Country 34630 0
Australia
Phone 34630 0
+61 8 8404 2841
Fax 34630 0
Email 34630 0
graeme.young@flinders.edu.au
Contact person for public queries
Name 17877 0
Ms Jane Upton
Address 17877 0
Department of Gastroenterology
Flinders Medical Centre
Bedford Park
SA 5042
Country 17877 0
Australia
Phone 17877 0
61 8 82046071
Fax 17877 0
61 8 82046330
Email 17877 0
jane.upton@health.sa.gov.au
Contact person for scientific queries
Name 8805 0
Dr Ying Hu
Address 8805 0
Flinders University
Department of Gastroenterology
Bedford Park
SA 5042
Country 8805 0
Australia
Phone 8805 0
6108082045170
Fax 8805 0
Email 8805 0
ying.hu@flinders.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary