Trial Information

Energy Balance Interventions for Colorectal Cancer Prevention

OBJECTIVES:

- To compare four 12-week energy-balance interventions comprising a physical activity
intervention (+2,000 kcal/wk), a dietary energy restriction intervention (DER)(-2,000
kcal/wk), or a combined physical activity and DER intervention (+1,000/-1,000 kcal/wk)
vs no intervention in healthy, overweight, or moderately obese participants at
increased risk for developing colorectal cancer.

- To quantify changes in circulating biomarkers (e.g., insulin, IGF-1, leptin, c-reactive
protein, or isoprostanes) proposed to mediate the anticarcinogenic effects of DER in
these participants.

OUTLINE: This study consists of a 2-week run-in period (baseline) followed by a 12-week
intervention period.

Participants undergo three study visits at Vanderbilt University General Clinical Research
Center (GCRC). Beginning at study visit 1, participants undergo a 2-week run-in period to
obtain baseline measures of body composition (via dual x-ray absorptiometry),
cardiorespiratory fitness (via treadmill testing), physical activity, dietary intake, energy
expenditure, and metabolic activity. Dietary assessments using 24-hour dietary recalls are
conducted by the GCRC dietitian during the run-in period. GCRC dietitians complete three
24-hour recalls on randomly selected days during the 2-week assessment period to provide an
estimate of the participant's habitual food intake at baseline. Baseline energy needs are
assessed during activity monitored run-in period to obtain measures of the participant's
resting energy expenditure and total daily energy expenditure. Participants are also
assessed using a brief psychological profile that is used to individualize the study
intervention for each participant.

Approximately 10-14 days after the initial visit and after all baseline assessments have
been completed, participants undergo a second study visit. Participants are randomized to 1
of 4 intervention arms.

- Arm I (physical activity): Participants undergo an in-person, 30- to 60-minute
counseling visit, followed by five brief 10- to 15-minute telephone-counseling calls
over 12 weeks. During the initial counseling session, participants learn about goal
setting and how to develop a personalized plan for meeting their intervention goals.
Participants are instructed about wearing proper shoes and about monitoring their
exercise duration and intensity. Participants are also given pedometers to help track
their activity patterns and to monitor their progress in meeting program objectives.
Participants must wear the pedometers for 7 days at baseline and again at 12 weeks. The
information provided is used to estimate overall physical activity energy expenditure
(PAEE), steps per day, and time spent in different levels of activity.

Participants are monitored periodically for adherence to the exercise program through
behavioral counseling and self-reported logs of daily exercise and pedometer steps. Dietary
intake is measured periodically using multiple 24-hour dietary recalls to carefully assess
possible changes in energy intake and dietary quality over the course of the study.

- Arm II (dietary energy restriction [DER]): Based on the initial estimate of energy
needs determined during the run-in period, participants receive a reduced-calorie, food
exchange-based diet for 12 weeks. Each diet is individualized to achieve the desired
daily energy deficit of 300 calories per day based on physical activity levels. All
meals are prepared by the GCRC metabolic kitchen. Participants receive one multivitamin
per day and no other nutritional supplements. Fluids including coffee, water, and other
drinks are allowed at the pre-study level. Each week, participants meet with the
dietitian to discuss the participant's progress, submit daily reports of food intake,
return uneaten food items, and to provide urine samples for assessment of urinary
biomarkers.

Adherence to the diet is monitored by compliance with food pick-up, dietary records, and
measures of urinary metabolites. Participants are also provided with individual instruction,
counseling, and assessment by the study dietitian.

- Arm III (physical activity and DER): Participants undergo a 12-week DER and
physical-activity program, as described in arms I and II, with the exception that the
dose of PAEE and DER in the combined intervention (i.e., +1,000/-1,000 kcal/week) is
half that of each individual intervention (+2,000 kcal/week for arm I and -2,000
kcal/week for arm II). Participants in arm III receive an individualized
reduced-calorie diet designed to achieve a desired daily energy deficit of 150 calories
per day based on participant physical activity levels.

- Arm IV (wait-list control): Participants are followed periodically. At study visit 3,
after completion of the 12-week study interventions, participants undergo repeat
assessment of body composition, fitness, diet, and activity measures.

Participants undergo blood and urine sample collection at baseline and at 12 weeks for
correlative laboratory studies. Blood samples are assessed for circulating biomarkers that
are involved in energy homeostasis and metabolic control (e.g., insulin, IGF, and leptin)
and inflammation and oxidative stress (e.g., c-reactive protein, PGE-2, and isoprostanes).
Urine samples are examined for biomarkers of dietary protein intake (i.e., nitrogen
content), dietary sodium, and potassium intake.

Participants complete the Community Health Activities Model Program for Seniors Physical
Activity Questionnaire at baseline and at 12 weeks for assessment of PAEE through
non-occupational activities, including social activities, recreation, hobbies, housework,
walking, jogging, and 14 other types of exercise.