Effect of Weight Loss on Prostate Cancer Pathology

Obesity Clinical Trial

Official title:

Effect of Weight Loss on Prostate Cancer Pathology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00475982
• Other study ID #: CLIN-012-06F
• Status: Completed
• Phase: N/A
• Start date: January 2009
• Est. completion date: March 2016

Study information

• Verified date: August 2018
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Prostate Cancer
• Prostatic Neoplasms
• Weight Loss

Intervention

Behavioral:
• Weight Loss
Subjects undergo a weight loss intervention prior to radical prostatectomy. The intervention includes weekly visits with the dietician, DEXA scanning, blood draws, and anthropometrics.

Other:
• No Weight Loss Group
These subjects do not undergo a weight loss intervention prior to radical prostatectomy. This group does undergo DEXA scanning, blood draws, and anthropometrics prior to radical prostatectomy.

Locations

Country	Name	City	State
United States	VA Greater Los Angeles Healthcare System, West Los Angeles, CA	West Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention	The primary objective is to compare the mean apoptotic index in the radical prostatectomy malignant epithelium between the Weight Loss Group and the Control Group-No Weight Loss. The apoptotic index will be measured in the malignant epithelium with the highest Gleason grade. TUNEL staining was used to identify these apoptotic cells and measure the apoptotic index, which is the percent of cells stained from the sample.	8 weeks
Secondary	Proliferative Index in Prostate Cancer Epithelium Specimen	The proliferative index in prostate cancer epithelium obtained from the radical prostatectomy specimen. This index was procured by staining the Ki67 protein to measure cell proliferation. (Note: Ki67 is a common indicator of cell proliferation.)	8 weeks
Secondary	Change in Serum IGF-related Analytes: IGF-1	This outcome is the measure of the hormone insulin-like growth factor 1 at baseline vs. post-intervention. We measured and compared the concentration (ng/mL) of this hormone.	baseline and post-intervention
Secondary	Change in Serum IGF-related Analytes: IGFBP-1	This outcome is the measure of the protein, insulin-like growth factor binding protein 1, at baseline vs. post-intervention. We measured and compared the concentration (ng/mL) of this protein.	baseline and post-intervention
Secondary	Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells	The BRDU assay measures proliferation of cultured cells such as LNCaP. We expose the cells to the patient blood and see if it inhibits prostate cancer cell growth ex vivo. We use optical density (a measure of the amount of light able to pass through the specimen) to indicate the concentration of cell proliferation.	baseline and post-intervention
Secondary	Change in Body Weight	This change in body weight is observed by DEXA, a scanner that measures total body composition.	baseline and post-intervention
Secondary	Change in Percent Body Fat	This change in percent body fat is observed by DEXA, a scanner that measures total body composition.	baseline and post-intervention