Clinical trial NCT00475982: Effect of Weight Loss on Prostate Cancer Pathology
Official title: Effect of Weight Loss on Prostate Cancer Pathology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Prostate Cancer
Keywords: Diet
Insulin-like Growth Factor
Weight Loss
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2007-05-21
Enrollment: 44
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine if weight loss prior to radical prostatectomy effects chemical substances in the blood stream and prostate tissue that may affect prostate cancer development and progression.

Detailed description: Obesity is an epidemic, a major public health concern, and is a significant risk factor for progression and mortality from prostate cancer. Prior work in the investigators' laboratory in pre-clinical prostate cancer models and in obese men found that a low fat diet, exercise, and weight loss resulted in antiproliferative and pro-apoptotic effects on prostate cancer tissue through mechanisms related to the IGF-axis. The investigators now propose to conduct a prospective, randomized clinical trial in overweight and obese men with prostate cancer undergoing radical prostatectomy to evaluate if weight loss prior to radical prostatectomy results in antiproliferative and pro-apoptotic effects in prostate cancer tissue. The investigators will accomplish this aim by enrolling overweight and obese men with prostate cancer scheduled to undergo radical prostatectomy. Following informed consent, men will be randomized to either immediate radical prostatectomy or to an 8-week weight loss intervention group that will undergo a diet and exercise weight loss program followed by radical prostatectomy. Proliferation and apoptosis of prostate cancer cells in the prostatectomy specimen will be compared between the groups and relative to the baseline prostate needle biopsy specimens. Further studies will evaluate potential serum surrogate biomarkers that the investigators developed in the investigators' laboratory (ex-vivo serum bioassays) and serum and tissue IGF-axis proteins that have previously been related to obesity, weight loss, and prostate cancer progression. The goal of the investigators' project will be to evaluate the potential anticancer effects of weight loss on prostate cancer tissue and to identify surrogate serum biomarkers that reflect antiproliferative and pro-apoptotic tissue effects and can be applied to future secondary prevention trials in overweight and obese prostate cancer survivors.

Eligibility criteria: Inclusion Criteria:

* Subject is overweight or obese (BMI \> 25 kg/m2)
* Patient with pathologically confirmed adenocarcinoma of the prostate and has elected to undergo radical prostatectomy
* Willing to delay radical prostatectomy for 5 to 8-weeks if randomized to the weight loss intervention group.
* Able to adhere to physical activity intervention (able to walk for 30 minutes without rest)
* Able to come to the VA for weight loss visits during the 5 to 8-wk study

Exclusion Criteria:

* Any one of the following: Gleason grade \> 4+4, PSA \> 20.
* History of ever receiving androgen deprivation therapy, antiandrogen therapy, or finasteride
* Prior prostate radiotherapy (external beam or brachytherapy) or prior cryotherapy
* Diagnosis of diabetes mellitus and on insulin\*\*
* Current use of weight loss medications or enrolled in a diet/weight loss program
* Current use of lycopene supplements\*\*\* Significant co-morbidities (i.e. cardiac, pulmonary, liver disease, ongoing alcohol/drug abuse) Cardiac pacemaker

Primary outcomes:
measure: Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention
timeFrame: 8 weeks
Secondary outcomes:
measure: Proliferative Index in Prostate Cancer Epithelium Specimen
timeFrame: 8 weeks
measure: Change in Serum IGF-related Analytes: IGF-1
timeFrame: baseline and post-intervention
measure: Change in Serum IGF-related Analytes: IGFBP-1
timeFrame: baseline and post-intervention
measure: Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells
timeFrame: baseline and post-intervention
measure: Change in Body Weight
timeFrame: baseline and post-intervention
measure: Change in Percent Body Fat
timeFrame: baseline and post-intervention
Other outcomes:
Locations:
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
Study officials:
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
name: William Aronson, MD
role: PRINCIPAL_INVESTIGATOR
References: