NCT03028831

Brief Summary

Alaska native people (AN) have the highest recorded incidence and death rate from colon cancer in the world (\>90:100,000). We hypothesize that the AN, despite their high consumption of anti-inflammatory and antineoplastic n-3 fish oils, are at increased risk of colon cancer because of colonic butyrate deficiency resulting from their remarkably low consumption of fiber-containing foods. We hypothesize that fiber supplementation of their usual diet will result in a bloom of butyrate producing microbes in the colon, resulting in increased butyrate production, which will suppress their high microbial secondary bile acid production, antagonize the actions of other food (smoked fish) and environmental carcinogens (tobacco, alcohol), and interact with the high circulating levels of n-3 fish oils to suppress colonic inflammation and cancer risk. In order to investigate this, we will conduct a randomized double-blinded 4-week clinical trial in up to 100 randomizable healthy, middle-aged AN undergoing screening colonoscopy, with the objective of obtaining 60 completed interventions. The interventions will consist of either a high-dose soluble fiber supplement given as a drink, together with their usual diet which currently contains about 15g total fiber/d, or to a control digestible starch drink plus their usual diet. The primary endpoint will be a clinically significant reduction in Ki67 proliferative colonic mucosal biomarkers of cancer risk. Microbiome and metabolome mechanisms responsible for the anticipated changes in mucosal biomarkers will also be investigated. Our results in extreme risk AN will be further evaluated by comparison to similar measurements previously made in minimal risk rural Africans and intermediate risk African Americans. Our results will be used to provide the scientific basis for a definitive large-scale high-fiber supplementation study (to achieve \>50g total fiber/d) to suppress adenomatous polyp recurrence following colonoscopy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Dec 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 18, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 23, 2017

Completed
11 months until next milestone

Study Start

First participant enrolled

December 11, 2017

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

May 16, 2023

Status Verified

December 1, 2022

Enrollment Period

5.1 years

First QC Date

January 18, 2017

Last Update Submit

May 13, 2023

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

  • colonic mucosal proliferation

    biomarker of cancer risk

    4 weeks

Secondary Outcomes (2)

  • colonic microbiota

    4 weeks

  • colonic secondary bile acids

    4 weeks

Study Arms (2)

Resistant Starch

ACTIVE COMPARATOR

70g high-amylose maize starch which contains 42g of type 2 resistant starch

Dietary Supplement: Resistant starch

Digestible Starch

PLACEBO COMPARATOR

70g of fully digestible starch comprised of amylopectin corn starch.

Dietary Supplement: 70g of fully digestible starch amylopectin corn starch

Interventions

70g of fully digestible starch amylopectin corn starchDIETARY_SUPPLEMENT

Fully digestible amylopectin corn starch

Digestible Starch
Resistant starchDIETARY_SUPPLEMENT

70g high-amylose maize starch

Resistant Starch

Eligibility Criteria

Age40 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Alaskan Native Tribal Health Consortium

Anchorage, Alaska, 99508, United States

Location

Upittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

  • O'Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016 Dec;13(12):691-706. doi: 10.1038/nrgastro.2016.165. Epub 2016 Nov 16.

    PMID: 27848961BACKGROUND

  • O'Keefe SJ, Li JV, Lahti L, Ou J, Carbonero F, Mohammed K, Posma JM, Kinross J, Wahl E, Ruder E, Vipperla K, Naidoo V, Mtshali L, Tims S, Puylaert PG, DeLany J, Krasinskas A, Benefiel AC, Kaseb HO, Newton K, Nicholson JK, de Vos WM, Gaskins HR, Zoetendal EG. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015 Apr 28;6:6342. doi: 10.1038/ncomms7342.

    PMID: 25919227RESULT

  • Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, Gaskins HR, O'Keefe SJ. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013 Jul;98(1):111-20. doi: 10.3945/ajcn.112.056689. Epub 2013 May 29.

    PMID: 23719549RESULT

  • Koller KR, Wilson A, Normolle DP, Nicholson JK, Li JV, Kinross J, Lee FR, Flanagan CA, Merculieff ZT, Iyer P, Lammers DL, Thomas TK, O'Keefe SJD. Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol. BMJ Open. 2021 Aug 27;11(8):e047162. doi: 10.1136/bmjopen-2020-047162.

    PMID: 34452959RESULT

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Resistant Starch

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

StarchGlucansBiopolymersPolymersMacromolecular SubstancesDietary FiberDietary CarbohydratesCarbohydratesPolysaccharidesFoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Gabriela Riscuta

    National Cancer Institute (NCI)

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
similar packets, similar appearing supplements
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: dietary supplementation
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

January 18, 2017

First Posted

January 23, 2017

Study Start

December 11, 2017

Primary Completion

December 31, 2022

Study Completion

December 31, 2022

Last Updated

May 16, 2023

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will share

we will use a public deposit when all the data analysis is completed

Time Frame
2012
Access Criteria
public

Locations

US(2)