Pilot Trial of Resistant Starch in Stage I-III Colorectal Cancer Survivors

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03781778
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This phase II, randomized pilot trial studies the effect of the consumption of foods made with resistant starch compared to foods made with corn starch on biomarkers that may be related to colorectal cancer progression in stage I-III colorectal cancer survivors. Foods made with resistant starch may beneficially influence markers of inflammation, insulin resistance, and the composition of gut bacteria in colorectal cancer survivors.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer; Rectal Cancer; Cancer Survivor; Colorectal Adenocarcinoma; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8	Other: Dietary Intervention (resistant starch); Other: Dietary Intervention (regular starch); Other: Questionnaire Administration	Phase 2

Detailed Description

Participants are randomized to 1 of 2 groups.

GROUP I (INTERVENTION GROUP): Participants eat a diet consisting of resistant starch foods daily for 8 weeks. Study provided foods are in addition to their own usual daily diet.

GROUP II (CONTROL GROUP): Participants eat a diet consisting of regular corn starch foods daily for 8 weeks. Study provided foods are in addition to their own usual daily diet.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Blinded, block randomization based on sex and BMI.Blinded, block randomization based on sex and BMI.
• Masking: Double (Participant, Investigator)
• Masking Description: Assignment to the active versus control group will be blinded using a computer program and will be designated as "diet A" and "diet B". Investigators will be unblinded once the study and data analyses have been completed.
• Primary Purpose: Prevention
• Official Title: Randomized, Controlled Trial of Resistant Starch in Stage I-Ill Colorectal Cancer Survivors Pilot Study: The Fiber for Health After Cancer Study
• Actual Study Start Date: May 7, 2019
• Actual Primary Completion Date: Oct 1, 2020
• Actual Study Completion Date: Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I (resistant starch foods) Patients eat a diet consisting of resistant starch foods daily for 8 weeks.	Other: Dietary Intervention (resistant starch); Eat foods with resistant starch; Other Names: Dietary Modification intervention, dietary Nutrition Intervention Nutrition Interventions Nutritional Interventions ; Other: Questionnaire Administration; Ancillary studies
Active Comparator: Group II (foods with regular corn starch) Patients eat a diet consisting of regular corn starch foods daily for 8 weeks.	Other: Dietary Intervention (regular starch); Eat foods with regular corn starch; Other Names: Dietary Modification intervention, dietary Nutrition Intervention Nutrition Interventions Nutritional Interventions ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Feasibility: Accrual [Up to 12 months]

   The accrual rate will be estimated with number of participants at full enrollment at 12 months.

2. Feasibility: Adherence [From start of intervention to ending intervention: up to 8 weeks]

   The adherence endpoint pertains to adherence to the intervention and is defined as consuming 75% or more of study foods on 75% of days from baseline to 8 weeks.

3. Feasibility: Retention [From start of intervention to the 8-week timepoint]

   The retention endpoint is defined as at least 80% of enrolled participants providing blood and stool samples at the week 8 timepoint.

Secondary Outcome Measures

1. Variability of Biomarkers of Insulin Resistance and Inflammation (Adiponectin) [Baseline to follow-up at week 8]

   Adiponectin was measured at baseline and week 8 (follow-up) and reported using descriptive statistics.

2. Variability in Biomarkers of Insulin Resistance and Inflammation (C-reactive Protein, CRP) [Baseline to follow-up at week 8]

   CRP was measured at baseline and week 8 (follow-up) and reported using descriptive statistics.

3. Variability in Gut Microbial Communities From Human Stool Samples [Baseline to follow-up at weeks 2 and 8]

   This measure assesses variability in gut microbial communities from human stool samples collected during the study by changes in alpha diversity, global microbial community (beta diversity), and genera in response to the intervention. We will use multivariate and univariate approaches to assess significant changes in the microbiome in response to the intervention.

4. Fecal Microbiota From Resistant Starch Responders [Baseline to follow-up at weeks 2 and 8]

   Fecal microbiota from resistant starch responders (i.e., in individuals with significant resulting elevations in fecal short-chain fatty acids concentrations) will be selected as input samples in gnotobiotic mouse studies, in which mice will be fed diets with or without resistant starch in order to characterize effects on tumorigenesis in an otherwise controlled environment. We predict that the chemoprotective effect of this diet intervention will be dependent upon gut microbial metabolism.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of diagnosed American Joint Committee on Cancer (AJCC) stage I-III colorectal adenocarcinoma.

• Completed all treatment of colorectal adenocarcinoma within past 4-36 months.

• Current Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (per physician).

• Ability to consent and follow study protocol.

Exclusion Criteria:

• Active cancer.

• Prior diagnosis of diabetes that is currently uncontrolled (defined as hemoglobin [Hgb] A1c > 8.0).

• Active inflammatory bowel disease (i.e., patients who are symptomatic despite medical therapy). This includes irritable bowel syndrome, Crohn's disease, or any other inflammatory bowel disorder.

• Known food allergy/intolerances to wheat, gluten, dairy or eggs.

• Use of antibiotic(s) within the last 3 months prior to enrollment.

• Women who are pregnant and/or breastfeeding.

• Current body mass index (BMI) < 18.5 kg/m^2.

• Uncontrolled constipation.

• Inability to speak and fully understand English.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marian Neuhouser, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 4, 2020

More Information

Publications

None provided.

• Responsible Party: Marian Neuhouser, Professor, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT03781778
• Other Study ID Numbers: RG1003387; NCI-2018-02802; 10079; P30CA015704
• First Posted: Dec 20, 2018
• Last Update Posted: Jan 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Marian Neuhouser, Professor, Fred Hutchinson Cancer Center: Resistant Starch; Colorectal Cancer
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Period Title: Overall Study
STARTED	4	6
Started Intervention	3	4
COMPLETED	2	4
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)	Total
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Total of all reporting groups
Overall Participants	4	6	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 50%	4 66.7%	6 60%
>=65 years	2 50%	2 33.3%	4 40%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	50	58.5
Sex: Female, Male (Count of Participants)
Female	1 25%	2 33.3%	3 30%
Male	3 75%	4 66.7%	7 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	6 100%	10 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 16.7%	1 10%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	5 83.3%	9 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	6 100%	10 100%
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	177.54	173.75	176.00
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	85.88	88.95	85.90
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	27.7	27.2	27.65
BMI Category (Count of Participants)
Underweight	0 0%	0 0%	0 0%
Normal weight	1 25%	3 50%	4 40%
Overweight	2 50%	0 0%	2 20%
Obese I	1 25%	2 33.3%	3 30%
Obese II+	0 0%	1 16.7%	1 10%
T-stage (Count of Participants)
T0	0 0%	0 0%	0 0%
T1	0 0%	0 0%	0 0%
T2	0 0%	1 16.7%	1 10%
T3	3 75%	5 83.3%	8 80%
T4a	1 25%	0 0%	1 10%
T4b	0 0%	0 0%	0 0%
N-stage (Count of Participants)
N0	0 0%	2 33.3%	2 20%
N1	1 25%	0 0%	1 10%
N1a	1 25%	1 16.7%	2 20%
N1b	0 0%	1 16.7%	1 10%
N1c	1 25%	2 33.3%	3 30%
N2	1 25%	0 0%	1 10%
N2a	0 0%	0 0%	0 0%
N2b	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Feasibility: Accrual
Description	The accrual rate will be estimated with number of participants at full enrollment at 12 months.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Measure Participants	4	5
Count of Participants [Participants]	4 100%	5 83.3%

2. Primary Outcome

Title	Feasibility: Adherence
Description	The adherence endpoint pertains to adherence to the intervention and is defined as consuming 75% or more of study foods on 75% of days from baseline to 8 weeks.
Time Frame	From start of intervention to ending intervention: up to 8 weeks

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed for the adherence measure: 7 (per protocol)

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Measure Participants	3	4
Count of Participants [Participants]	2 50%	4 66.7%

3. Primary Outcome

Title	Feasibility: Retention
Description	The retention endpoint is defined as at least 80% of enrolled participants providing blood and stool samples at the week 8 timepoint.
Time Frame	From start of intervention to the 8-week timepoint

Outcome Measure Data

Analysis Population Description

All participants enrolled, in accordance with protocol and Statistical Analysis Plan

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Measure Participants	4	6
Count of Participants [Participants]	3 75%	5 83.3%

4. Secondary Outcome

Title	Variability of Biomarkers of Insulin Resistance and Inflammation (Adiponectin)
Description	Adiponectin was measured at baseline and week 8 (follow-up) and reported using descriptive statistics.
Time Frame	Baseline to follow-up at week 8

Outcome Measure Data

Analysis Population Description

Of the 10 participants enrolled to the study, blood was collected at the baseline and week 8 follow-up timepoints on just 5 participants.

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Measure Participants	2	3
Adiponectin - baseline	1.33 (0.54)	1.95 (0.95)
Adiponectin - followup	1.14 (0.55)	2.08 (1.11)

5. Secondary Outcome

Title	Variability in Biomarkers of Insulin Resistance and Inflammation (C-reactive Protein, CRP)
Description	CRP was measured at baseline and week 8 (follow-up) and reported using descriptive statistics.
Time Frame	Baseline to follow-up at week 8

Outcome Measure Data

Analysis Population Description

Of the 10 participants enrolled to the study, blood was collected at the baseline and week 8 followup timepoints on just 5 participants.

Arm/Group Title	1-Active (Resistant Starch)	2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.	Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
Measure Participants	2	3
C-reactive protein - baseline	1.24 (0.74)	1.98 (2.13)
C-reactive protein - followup	1.93 (2.37)	1.67 (1.77)

6. Secondary Outcome

Title	Variability in Gut Microbial Communities From Human Stool Samples
Description	This measure assesses variability in gut microbial communities from human stool samples collected during the study by changes in alpha diversity, global microbial community (beta diversity), and genera in response to the intervention. We will use multivariate and univariate approaches to assess significant changes in the microbiome in response to the intervention.
Time Frame	Baseline to follow-up at weeks 2 and 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Fecal Microbiota From Resistant Starch Responders
Description	Fecal microbiota from resistant starch responders (i.e., in individuals with significant resulting elevations in fecal short-chain fatty acids concentrations) will be selected as input samples in gnotobiotic mouse studies, in which mice will be fed diets with or without resistant starch in order to characterize effects on tumorigenesis in an otherwise controlled environment. We predict that the chemoprotective effect of this diet intervention will be dependent upon gut microbial metabolism.
Time Frame	Baseline to follow-up at weeks 2 and 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From start of intervention to ending the intervention: up to 8 weeks.
Adverse Event Reporting Description	Method of assessment: weekly participant-completed questionnaire. The number of participants (n=7) analyzed for adverse events ("number at risk" below) is fewer than the number enrolled (n=10) because 3 participants withdrew consent prior to starting the intervention.
Arm/Group Title	1-Active (Resistant Starch)		2-Control (Regular Starch)
Arm/Group Description	Participants receive daily study snack foods prepared with resistant starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.		Participants receive daily study snack foods prepared with regular starch. Dosing is 15g of starch daily for the first 14 days, then 30g of starch daily for the remaining 42 days.
All Cause Mortality
	1-Active (Resistant Starch)		2-Control (Regular Starch)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Serious Adverse Events
	1-Active (Resistant Starch)		2-Control (Regular Starch)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	1-Active (Resistant Starch)		2-Control (Regular Starch)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		4/4 (100%)
Gastrointestinal disorders
Gassiness	2/3 (66.7%)	2	4/4 (100%)	4
Bloating	1/3 (33.3%)	1	3/4 (75%)	3
Increased frequency of bowel movements	1/3 (33.3%)	1	2/4 (50%)	2
Heartburn	1/3 (33.3%)	1	0/4 (0%)	0
Abdominal discomfort	0/3 (0%)	0	1/4 (25%)	1
Loose stool	0/3 (0%)	0	2/4 (50%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.