Effect of Exercise on Biomarkers of Colon Cancer Risk - Full Text View

Sponsored by:	Fred Hutchinson Cancer Research Center
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00668161

Purpose

There is strong observational epidemiologic evidence that physical activity is inversely associated with risk of colon cancer occurrence in both men and women. This association has been found in over 30 observational studies, and appears to be independent of effects of diet, body fat mass, and other potential confounding factors. Prior to large-scale recommendations regarding exercise as a means of preventing colon cancer, however, more information is needed regarding the type of exercise, when it must be initiated, and how much must be done, in order to produce a protective effect. Information on the mechanisms and biological pathways through which exercise might protect the colon will aid in developing the answers to these questions.

This is a randomized controlled trial of a one-year moderate/vigorous exercise intervention vs. delayed- exercise control on various biomarkers of colon cancer risk in persons that have undergone a colonoscopy within the past 36 months.. The trial is designed to establish the effects of the exercise intervention on colorectal cell proliferation and terminal differentiation, and on factors that may lie in the pathway between exercise and proliferation and apoptosis, in colon and rectal epithelium. It will provide data on: 1) the efficacy of a one-year moderate intensity aerobic exercise program in modulating these processes to a pattern considered low risk for colon cancer, and 2) the mechanisms whereby exercise may lower colon cancer risk in humans. To the investigators' knowledge, this will be the first study of its kind.

Condition	Intervention	Phase
Colon Cancer Prevention	Behavioral: Exercise Behavioral: Delayed Exercise	Phase II Phase III

MedlinePlus related topics: Cancer Exercise and Physical Fitness

Drug Information available for: BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Investigator), Single Group Assignment, Efficacy Study
Official Title:	Exercise Intervention Trial for Colorectal Polyp Patients

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Proliferation rate in the upper part of colon and rectal mucosa crypts. [ Time Frame: Baseline and 12-months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

expression of apoptosis-related proteins (bax/bcl-2 ratio) in colon and rectal mucosal biopsies [ Time Frame: Baseline and 12-months ] [ Designated as safety issue: No ]
rectal mucosal prostaglandin levels [ Time Frame: baseline and 12-months ] [ Designated as safety issue: No ]
fasting serum/plasma insulin, glucose, triglycerides, insulin-like growth factor 1(IGF-1), and IGF binding protein-3 (IGFPB-3) [ Time Frame: baseline and 12-months ] [ Designated as safety issue: No ]
body fat mass and distribution (body mass index, waist and hip circumferences, bioelectrical impedance, DEXA scan)and subcutaneous abdominal and intra-abdominal fat mass (measured by one-slice CT scan at the L4 level) [ Time Frame: baseline and 12-months ] [ Designated as safety issue: No ]
quality of life (measured by standardized self-report instruments) and sleep quality [ Time Frame: baseline and 12-months ] [ Designated as safety issue: No ]

Enrollment:	202
Study Start Date:	January 2001
Estimated Study Completion Date:	December 2018
Primary Completion Date:	December 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Exercise	Behavioral: Exercise 60 minutes/session of aerobic exercise, 6 d/week at 50-50% HHR. All sessions will begin with 10 minutes of stretching and 5 minutes of warm-up, and will end with 5 minutes of cool down.
2: No Intervention Control	Behavioral: Delayed Exercise Participants in the Delayed Exercise Controls Group will have scheduled clinic visits at baseline, 3, 6, 9 and 12 months. After their end-of-the 12 month study assessments, they will be offered the chance to meet with the exercise physiologist individually to learn aerobic exercise techniques.

Detailed Description:

The specific aims of the proposed study are:

To measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. a delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on proliferation rate in the upper part of colon and rectal mucosa crypts.
To also measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on:
- expression of apoptosis-related proteins (bax/bcl-2 ratio) in colon and rectal mucosal biopsies
- rectal mucosal prostaglandin levels
- fasting serum/plasma insulin, glucose, triglycerides, insulin-like growth factor 1(IGF-1), and IGF binding protein-3 (IGFPB-3)
- body fat mass and distribution (body mass index, waist and hip circumferences, bioelectrical impedance, DEXA scan)
- subcutaneous abdominal and intra-abdominal fat mass (measured by one-slice CT scan at the L4 level)
- fitness (VO2max)
- quality of life (measured by standardized self-report instruments)
- sleep quality

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male or female
Completed a colonoscopy within the past 36 months
Ages 40-75 years at time of identification
Sedentary activity pattern
Gives informed consent, agrees to be randomly assigned
Able to perform all study requirements, able to follow directions and complete forms

Exclusion Criteria:

Colorectal cancer at any time; any other invasive cancer within the past 10 years (simple basal or squamous cell carcinoma okay)
Plans to leave Western Washington during the follow-up period
Morbidly obese (BMI > 41), weight loss of > 10 pounds in the previous 3 months
Familial polyposis, Gardner's syndrome, or other known familial colorectal cancer syndrome
Ulcerative colitis or short bowel
"Excessive"(> 3 x week) laxative or enema use that might interfere with rectal crypt studies
Current use of certain medications likely to interfere with success of the intervention, or with outcomes measures (for example, anticoagulants because of risk from colorectal biopsy, diet medications within past 6 months)
Diabetes mellitus or fasting glucose > 140
Hemochromatosis- if diagnosed by physician
Abnormal screening labs (hematocrit < 32 or > 48, white blood cells < 3.0 or > 15.0, potassium < 3.5 or > 5.3, fasting glucose > 140, creatinine > 2.0), or abnormalities on screening physical exam judged by study physicians to contraindicate participation in an exercise program
Contraindications for entry into a training program 131 including: unstable angina, uncontrolled hypertension (systolic > 200, diastolic > 100), orthostatic hypotension (>20 mm fall in systolic), moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, third degree heart block, pericarditis, myocarditis, pulmonary/systemic embolism within the past 6 months, thrombophlebitis, ST displacement > 3 mm at rest, history of cardiac arrest)
Contraindications for exercise testing 131 including: recent (within 6 months) cardiac event (MI, pulmonary edema, myocarditis, pericarditis), unstable angina, uncontrolled arrhythmia, third degree heart block, left bundle branch block, acute congestive failure, recent (within 6 months) pulmonary/systemic embolus, severe electrolyte abnormality
Meets criteria to stop screening exercise test 131 as decided by overseeing physician
Volunteering in order to lose weight; alcohol or drug abuse, significant mental or emotional problems such as would interfere with compliance (as assessed by study staff impression)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668161

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98102

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

More Information

Publications of Results:

Hawkins VN, Foster-Schubert K, Chubak J, Sorensen B, Ulrich CM, Stancyzk FZ, Plymate S, Stanford J, White E, Potter JD, McTiernan A. Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med Sci Sports Exerc. 2008 Feb;40(2):223-33.

Abrahamson PE, King IB, Ulrich CM, Rudolph RE, Irwin ML, Yasui Y, Surawicz C, Lampe JW, Lampe PD, Morgan A, Sorensen BE, Ayub K, Potter JD, McTiernan A. No effect of exercise on colon mucosal prostaglandin concentrations: a 12-month randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2351-6.

Campbell KL, McTiernan A, Li SS, Sorensen BE, Yasui Y, Lampe JW, King IB, Ulrich CM, Rudolph RE, Irwin ML, Surawicz C, Ayub K, Potter JD, Lampe PD. Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1767-74.

McTiernan A, Sorensen B, Irwin ML, Morgan A, Yasui Y, Rudolph RE, Surawicz C, Lampe JW, Lampe PD, Ayub K, Potter JD. Exercise effect on weight and body fat in men and women. Obesity (Silver Spring). 2007 Jun;15(6):1496-512.

McTiernan A, Yasui Y, Sorensen B, Irwin ML, Morgan A, Rudolph RE, Surawicz C, Lampe JW, Ayub K, Potter JD, Lampe PD. Effect of a 12-month exercise intervention on patterns of cellular proliferation in colonic crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1588-97.

Responsible Party:	Fred Hutchinson Cancer Research Center ( Anne McTiernan, MD, PhD )
Study ID Numbers:	APPEAL CA77572-01, FHCRC-4838, R01 CA77572-01
Study First Received:	April 24, 2008
Last Updated:	May 9, 2008
ClinicalTrials.gov Identifier:	NCT00668161
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Gastrointestinal Neoplasms

Polyps
Intestinal Diseases
Colonic Neoplasms
Intestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 16, 2009