Assisted Exercise in Obese Endometrial Cancer Patients

Study Overview
=================
Brief Summary
-----------------
This is an assisted exercise trial involving exercise on a stationary bike, brain imaging and DNA(genetics)sampling. The purpose of this study is to find out if performing a progressive, supervised assisted exercise program on a stationary bike improves quality of life, increases motivation to continue to exercise, improves dietary behavior and leads to sustained weight loss in women who have had early-stage endometrial cancer. Questionnaires will be used to assess exercise motivation and dietary behavior. Brain's responses to different visual images will also be assessed.

Detailed Description
-----------------
Primary Objective: To evaluate changes in body weight, fitness, bi-manual dexterity, exercise motivation and self-reported eating behavior (via questionnaires) before and after a 16-week exercise intervention (EOT) and 12 and 24 weeks post-EOT, in obese EC patients who will be randomized to perform 'assisted' or voluntary exercise. Secondary Objectives: Objective 1: To objectively examine food behavior as determined by neuronal response to high- versus low-calorie visual stimuli under fasted (hunger) and fed (satiated) states and stop/go signaling (SST) in fed states in brain regions of interest (reward and motivation circuitry) using blood oxygenation level dependent (BOLD) functional MRI before and after a 16-week exercise intervention (EOT) and 12 and 24 weeks post-intervention in obese EC patients performing 'assisted' and voluntary exercise. Objective 2: To examine the modification of the neuronal response to high vs. low calorie food images in regions of interest by polymorphisms in key genes (e.g., dopamine receptor and dopamine transporter) and serum biomarkers (e.g., leptin, BDNF) involved in regulating homeostatic and non-homeostatic energy systems. Patients will be randomized to receive either the assisted exercise (n=60) or voluntary exercise (n=60) group. Subjects in the voluntary group will exercise on a stationary recumbent exercise cycle and pedal at their preferred rate. Subjects in the assisted exercise group will cycle on the same stationary exercise bike; however, a motor will provide assistance to the patient in order to maintain a pedaling rate 35% greater than their voluntary rate. Subjects in the exercise groups will complete 45 minute to 1-hour sessions, three times per week for eight weeks. The control group will be asked to complete all exercise, body composition and fMRI testing similar to the exercise groups.

Official Title
-----------------
REWARD (Revving-Up Exercise for Sustained Weight Loss by Altering Neurological Reward and Drive): A Randomized Trial of Assisted Exercise in Obese Endometrial Cancer Patients

Conditions
-----------------
Stage I Endometrial Adenocarcinoma, Uterine Cancer, Obesity

Intervention / Treatment
-----------------
* Behavioral: Exercise on stationary recumbent exercise cycle
* Behavioral: Health Education
* Behavioral: Questionnaires
* Procedure: Neuroimaging
* Procedure: Genetic and Biomarkers


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed Stage I endometrial adenocarcinoma (EC), grade 1 or 2, with no adjuvant chemotherapy. Patients will be eligible to enroll as soon as 3 months after completion of treatment but no later than 4 years after completion of treatment. BMI ≥ 30.0 (obese) Approved to be contacted by the patient's treating gynecologic oncologist Meets screening criteria including successful completion of a cardiopulmonary stress test Receives medical clearance from the patient's primary care physician (PCP) or gynecologic oncologist to exercise in this study Exclusion Criteria: Individuals unable to read and provide informed consent. Women currently participating in a structured weight loss or exercise program in the past 6 months or any woman who has previously had bariatric surgery or is planning to undergo bariatric surgery in the next 12 months Participants who do not consent to be in the study or who will be unavailable for follow-up assessments, Pre-existing medical conditions that would be a barrier for participation in supervised exercise

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 'Assisted-Rate' Exercise Intervention<br>Subjects in the assisted exercise group will cycle on the same stationary exercise bike; however, a motor will provide assistance to the patient in order to maintain a pedaling rate 35% greater than their voluntary rate. Subjects in the exercise groups will complete 45 minute to 1-hour sessions, three times per week for eight weeks. | Behavioral: Exercise on stationary recumbent exercise cycle<br> <br> Behavioral: Health Education<br>* Informational brochure (Better Health and You, Weight Control Information Network, June, 2004)<br>Behavioral: Questionnaires<br> <br> * Other names: Godin Leisure-Time Exercise (LSI);Procedure: Neuroimaging<br>* Imaging data will be acquired on a Siemens 3.0T Wide-Bore Verio MRI scanner.<br>* Other names: MRI;Procedure: Genetic and Biomarkers<br>* Patients will be asked to fast for approximately 12 hours and will have approximately 2 Tbs. of blood drawn at baseline and the end of treatment (EOT).<br>* Other names: Biomarker Testing;|
| Experimental: 'Voluntary-Rate' Exercise Intervention<br>Subjects in the voluntary group will exercise on a stationary recumbent exercise cycle and pedal at their preferred rate. Subjects in the exercise groups will complete 45 minute to 1-hour sessions, three times per week for eight weeks. | Behavioral: Exercise on stationary recumbent exercise cycle<br> <br> Behavioral: Health Education<br>* Informational brochure (Better Health and You, Weight Control Information Network, June, 2004)<br>Behavioral: Questionnaires<br> <br> * Other names: Godin Leisure-Time Exercise (LSI);Procedure: Neuroimaging<br>* Imaging data will be acquired on a Siemens 3.0T Wide-Bore Verio MRI scanner.<br>* Other names: MRI;Procedure: Genetic and Biomarkers<br>* Patients will be asked to fast for approximately 12 hours and will have approximately 2 Tbs. of blood drawn at baseline and the end of treatment (EOT).<br>* Other names: Biomarker Testing;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight change from pre- to post-intervention |  | 24 weeks after exercise intervention (EOT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Composition from baseline | Body fat, lean mass and bone mass will be measured with a Lunar iDXA™ (GE Healthcare, Madison, WI. BMI will be computed (weight in kg divided by square of height in meters) and categorized as: < 18.5 (underweight), 18.5 to 24.9 (normal weight), 25.0 to 29.9 (overweight) | at 4 weeks after exercise intervention(EOT) | 
| Change in Motivation to Exercise from baseline | Evaluate motivation to exercise using the Exercise Motivations Inventory (EMI-2) 122 and the Intrinsic Motivational Inventory (IMI) modified for exercise. Past physical activity habits will be assessed with the Godin Leisure-Time Exercise (LSI) questionnaire. | 24 weeks after exercise intervention (EOT) | 
| Change in Eating Behavior from baseline | Eating behavior will be assessed using the Three-Factor Eating Questionnaire (TFEQ). The TFEQ includes 51 items and addresses three dimensions of human eating behavior; restraint, disinhibition, and perceived hunger. | 24 weeks after exercise intervention (EOT) | 
| Change in Quality of Life (QoL)from baseline | The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item core questionnaire evaluating various domains of QoL including, physical, functional, family-social, and emotional well-being. The FACT-En is a 16-item subscale specific for endometrial cancer (EC) and assesses hormone withdrawal, pelvic symptoms, and possible adjuvant therapy side effects. Short-form Medical Outcomes (SF-36) consists of 36 questions scored on a Likert scale, producing overall physical and mental component summary measures. | 24 weeks after exercise intervention (EOT) | 
| Change in Depression from baseline | The Beck Depression Inventory (BDI) is a 21-item, Likert-scaled instrument of depressive symptoms that is well-validated and frequently used in lifestyle research studies. Each item is rated on a 4- point scale ranging from 0 to 3 (higher scores are associated with greater symptoms). | 24 weeks after exercise intervention (EOT) | 
| Exercise Session Adherence | Barriers to adhering to the exercise protocol will be assessed prospectively using an elicitation procedure similar to that suggested in the theory of planned behavior, whereby an open-ended question is asked to solicit the barrier without any preconceived notion of what the barrier might be. Specifically, participants in the exercise groups will be asked to book their weekly supervised exercise sessions with the Exercise Specialist/Physiologist. Participants cancelling an exercise session or requesting to be removed from the study will be asked why they are no longer interested in completed the program. | 24 weeks after exercise intervention (EOT) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stage I endometrial adenocarcinoma, Obesity, Exercise and Physical Fitness, Diet, Cancer