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Fiber to Reduce Colon Cancer in Alaska Native People

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ClinicalTrials.gov Identifier: NCT03028831
Recruitment Status : Completed
First Posted : January 23, 2017
Last Update Posted : May 16, 2023
Sponsor:
Collaborator:
Alaska Native Tribal Health Consortium
Information provided by (Responsible Party):
Stephen O'Keefe, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE January 18, 2017
First Posted Date  ICMJE January 23, 2017
Last Update Posted Date May 16, 2023
Actual Study Start Date  ICMJE December 11, 2017
Actual Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
colonic mucosal proliferation [ Time Frame: 4 weeks ]
biomarker of cancer risk
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
  • colonic microbiota [ Time Frame: 4 weeks ]
    fecal and colonic microbiota analysis
  • colonic secondary bile acids [ Time Frame: 4 weeks ]
    fecal and colonic conjugated bile acid analysis
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fiber to Reduce Colon Cancer in Alaska Native People
Official Title  ICMJE Randomized Controlled Trial of Resistant Starch to Reduce Colon Cancer Risk in Alaska Native People.
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.
Detailed Description

Randomization for the double blind, placebo controlled, clinical trial: Recruitment will continue until 60 volunteers have completed the intervention study. Based on previous experience with similar studies, we anticipate 20% of screened patients to be ineligible or drop out, which means, so we plan on consenting and screening approximately 100 potential participants. Baseline data from these participants will be retained. Individuals will be randomized via minimisation (based on age, sex, polypectomy, high fish consumption, and BMI - factors that might influence microbiota composition and function)) to either the resistant starch (RS) group or the control digestible starch (DS) group upon completion of the Stabilization Period.

  1. RS Group: Participants will continue with their usual diet plus fiber supplement given as a daily dose of 70g high-amylose maize starch (HAM-RS, HI-MAIZE®260: Ingredion Incorporated, Bridgewater, NJ), which contains 42g of type 2 resistant starch, for 4 weeks. Data from previous studies[69] suggests that their usual diet will contain approximately 13g dietary fiber/day, chiefly insoluble, indicating that total fiber intake would be approx. 55g/d. Supplements will be pre-weighed out in batches from the same source and kept in airtight containers. The supplement may be taken as a single or divided dose dissolved in 250ml water, low fat milk, or orange juice
  2. DS (Control) Group participants will continue on their usual diet, plus 70g of fully digestible starch (waxy corn starch comprised of amylopectin, AMIOCA® corn starch, Ingredion Incorporated, Bridgewater, NJ ) weighed out, analyzed, and prepared as previously. The RS and control supplements will appear and taste similar, allowing for coding and distribution in a double-blind fashion. The supplements will be equicaloric.

Interventions will include fecal and colonic content sampling for measurement of the microbiome and metabolome, and flexible sigmoidoscopy to obtain mucosal biopsies before and after the dietary supplementation.

Monitoring During the Clinical Trial: This will follow the scheme laid out on Figure 7. On day 0, participants will visit the clinic and will be asked to save their first fecal sample using our standard operating procedure developed and proven to be effective in our last study. They will then be given their first supplement drink made up in their vehicle of choice, and taken with a standard meal provided by the diet kitchen. During the trial, they will be instructed on the use of a simple diary to be completed at home. This will record the major food items consumed each day, the timing and completion of drink supplements, as well as the bowel function questionnaire to assess daily GI tolerance, i.e. abdominal discomfort, distension, gas, bowel frequency, nausea, vomiting. They will be asked to return to the clinic for a follow-up appointment on day 7, 14 and 21 in order to repeat the fecal and breath tests described above. At the same time, body weight will be monitored using one scale. At the end of 4 weeks, participants will be asked to return to the clinic for repeat of the colonic sampling performed at baseline.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
dietary supplementation
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
similar packets, similar appearing supplements
Primary Purpose: Prevention
Condition  ICMJE Colon Cancer
Intervention  ICMJE
  • Dietary Supplement: 70g of fully digestible starch amylopectin corn starch
    Fully digestible amylopectin corn starch
  • Dietary Supplement: Resistant starch
    70g high-amylose maize starch
Study Arms  ICMJE
  • Active Comparator: Resistant Starch
    70g high-amylose maize starch which contains 42g of type 2 resistant starch
    Intervention: Dietary Supplement: Resistant starch
  • Placebo Comparator: Digestible Starch
    70g of fully digestible starch comprised of amylopectin corn starch.
    Intervention: Dietary Supplement: 70g of fully digestible starch amylopectin corn starch
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 13, 2023)
48
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2017)
60
Actual Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE Inclusion Criteria: Healthy AN volunteers (from GI standpoint) between 40-70 years (age at which colon cancer screening colonoscopy is recommended in this population) and BMI between 18-40 Kg/m2. It should be noted that in our previous study, we found no difference in the responses of the key parameters (mucosal biomarkers, butyrate and secondary bile acid producers, fecal SCFA and bile acids) to increased fiber diets between those with normal body weight, those overweight, and those who were obese (Nature Comm Supplement). Patients who have, or have had noncancerous polyps removed previously by colonoscopy will be eligible. Alaska Native race will be defined as those eligible to receive health care through the Alaska Tribal Health System. Exclusion criteria: These are detailed under Human Subjects. Participants will be ineligible if they have a history of familial adenomatous polyposis or hereditary non-polyposis colorectal cancer, or have previous colonoscopic evidence of inflammatory bowel disease or colon cancer. Also ineligible will be individuals with known renal, hepatic, or bleeding disorders; previous GI surgery resulting in disturbed gut function due to of loss of bowel or altered anatomy; or any form of chronic GI disease resulting in disturbed gut function, diarrhea, and malabsorption. Individuals with antibiotic use within the past 12 weeks, current steroids use, or on medical treatment for diabetes, will also be excluded.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03028831
Other Study ID Numbers  ICMJE PRO16080079
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: we will use a public deposit when all the data analysis is completed
Time Frame: 2012
Access Criteria: public
Current Responsible Party Stephen O'Keefe, University of Pittsburgh
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Pittsburgh
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Alaska Native Tribal Health Consortium
Investigators  ICMJE
Study Director: Gabriela Riscuta National Cancer Institute (NCI)
PRS Account University of Pittsburgh
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP