Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Weight Loss | Experimental | Weight Loss Group |
|
| Arm 2: No Weight Loss | Active Comparator | No Weight Loss Group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Weight Loss | Behavioral | Subjects undergo a weight loss intervention prior to radical prostatectomy. The intervention includes weekly visits with the dietician, DEXA scanning, blood draws, and anthropometrics. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| William Aronson, MD | VA Greater Los Angeles Healthcare System, West Los Angeles, CA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Greater Los Angeles Healthcare System, West Los Angeles, CA | West Los Angeles | California | 90073 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Weight Loss | Weight Loss Group 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. |
| FG001 | Arm 2: No Weight Loss | No Weight Loss Group 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: Weight Loss | Weight Loss Group 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. |
| BG001 | Arm 2: No Weight Loss |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | percentage of cells stained | 8 weeks |
|
8 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: Weight Loss | Weight Loss Group 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. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| William Aronson, MD | VA Medical Center Greater Los Angeles Healthcare System | 3102683446 | waronson@ucla.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 19, 2014 | Oct 11, 2017 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: VA GLA ICF | Apr 10, 2013 | Oct 11, 2017 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: UCLA ICF | Nov 10, 2011 | Aug 16, 2018 | ICF_002.pdf |
Not provided
| ID | Term |
|---|---|
| D009765 | Obesity |
| D011471 | Prostatic Neoplasms |
| D015431 | Weight Loss |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| No Weight Loss Group | Other | 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. |
|
| 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 |
| 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 |
| 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 |
| Change in Body Weight | This change in body weight is observed by DEXA, a scanner that measures total body composition. | baseline and post-intervention |
| 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 |
No Weight Loss Group 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Arm 2: No Weight Loss | No Weight Loss Group 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. |
|
|
|
| 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.) | Posted | Mean | Standard Deviation | percentage of cells stained | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. | Posted | Mean | Standard Deviation | density units | 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. | Posted | Mean | Standard Deviation | kg | 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. | Posted | Mean | Standard Deviation | percentage of body fat | baseline and post-intervention |
|
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Arm 2: No Weight Loss | No Weight Loss Group 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. | 0 | 21 | 0 | 21 |
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D001836 | Body Weight Changes |
| Change |
|
| 0.440 |
| Superiority |
| analysis between the weight loss and control arms | paired t-test | 0.186 | Mean Difference (Net) | 8.49 | 2-Sided | 95 | -4.31 | 21.3 | Superiority |
| Change |
|
| 0.986 |
| Superiority |
| analysis between the weight loss and control arms | paired t-test | 0.353 | Mean Difference (Net) | 2.22 | 2-Sided | 95 | -2.58 | 7.02 | Superiority |
| Change |
|
| 0.701 |
| Superiority |
| analysis between the intervention and control arms | paired t-test | 0.835 | Mean Difference (Net) | 0.77 | 2-Sided | 95 | -6.70 | 8.24 | Superiority |
| Change |
|
| 0.009 |
| Superiority |
| analysis between the two arms | paired t-test | 0.007 | Mean Difference (Net) | 2.11 | 2-Sided | 95 | 0.64 | 3.59 | Superiority |
| Change |
|
| 0.207 |
| Superiority |
| analysis between the two arms | paired t-test | 0.063 | Mean Difference (Net) | 1.34 | 2-Sided | 95 | -0.08 | 2.75 | Superiority |