Obesity, Prostate Cancer
Conditions
Keywords
Diet, Insulin-like Growth Factor, Weight Loss
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.
Interventions
BEHAVIORALWeight 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.
OTHERNo 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.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum IGF-related Analytes: IGF-1 | baseline and post-intervention | 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. |
| Change in Serum IGF-related Analytes: IGFBP-1 | baseline and post-intervention | 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. |
| Proliferative Index in Prostate Cancer Epithelium Specimen | 8 weeks | 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.) |
| Change in Body Weight | baseline and post-intervention | This change in body weight is observed by DEXA, a scanner that measures total body composition. |
| Change in Percent Body Fat | baseline and post-intervention | This change in percent body fat is observed by DEXA, a scanner that measures total body composition. |
| Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | baseline and post-intervention | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| 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. | 18 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | surgery rescheduled | 7 | 3 |
Baseline characteristics
| Characteristic | Arm 1: Weight Loss | Arm 2: No Weight Loss | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 22 Participants |
| Age, Continuous | 63.4 years STANDARD_DEVIATION 4.6 | 61.7 years STANDARD_DEVIATION 6.6 | 62.5 years STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 17 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 15 Participants | 26 Participants |
| Region of Enrollment United States | 16 participants | 18 participants | 44 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 21 |
| serious Total, serious adverse events | 0 / 23 | 0 / 21 |
Outcome results
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Weight Loss | Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention | 6.9 percentage of cells stained | Standard Deviation 10.4 |
| Arm 2: No Weight Loss | Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention | 5.0 percentage of cells stained | Standard Deviation 4.5 |
p-value: 0.965Wilcoxon (Mann-Whitney)
Secondary
Change in Body Weight
This change in body weight is observed by DEXA, a scanner that measures total body composition.
Time frame: baseline and post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Weight Loss | Change in Body Weight | Pre | 102.19 kg | Standard Deviation 17.15 |
| Arm 1: Weight Loss | Change in Body Weight | Post | 98.47 kg | Standard Deviation 16.78 |
| Arm 1: Weight Loss | Change in Body Weight | Change | -3.71 kg | Standard Deviation 1.85 |
| Arm 2: No Weight Loss | Change in Body Weight | Change | -1.60 kg | Standard Deviation 2.32 |
| Arm 2: No Weight Loss | Change in Body Weight | Pre | 101.02 kg | Standard Deviation 17.55 |
| Arm 2: No Weight Loss | Change in Body Weight | Post | 99.38 kg | Standard Deviation 16.42 |
Comparison: intra-analysis within the weight loss armp-value: 0paired t-test
Comparison: intra-analysis within the control armp-value: 0.009paired t-test
Comparison: analysis between the two armsp-value: 0.00795% CI: [0.64, 3.59]paired t-test
Secondary
Change in Percent Body Fat
This change in percent body fat is observed by DEXA, a scanner that measures total body composition.
Time frame: baseline and post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Weight Loss | Change in Percent Body Fat | Pre | 36.8 percentage of body fat | Standard Deviation 3.7 |
| Arm 1: Weight Loss | Change in Percent Body Fat | Post | 35.9 percentage of body fat | Standard Deviation 4.8 |
| Arm 1: Weight Loss | Change in Percent Body Fat | Change | -0.93 percentage of body fat | Standard Deviation 1.92 |
| Arm 2: No Weight Loss | Change in Percent Body Fat | Pre | 36.5 percentage of body fat | Standard Deviation 4.7 |
| Arm 2: No Weight Loss | Change in Percent Body Fat | Post | 36.9 percentage of body fat | Standard Deviation 5.4 |
| Arm 2: No Weight Loss | Change in Percent Body Fat | Change | 0.41 percentage of body fat | Standard Deviation 0.9 |
Comparison: intra-analysis within the weight loss armp-value: 0.073paired t-test
Comparison: intra-analysis within the control armp-value: 0.207paired t-test
Comparison: analysis between the two armsp-value: 0.06395% CI: [-0.08, 2.75]paired t-test
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.
Time frame: baseline and post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Change | 5.38 ng/mL | Standard Deviation 19.8 |
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Pre | 165.8 ng/mL | Standard Deviation 43.1 |
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Post | 171.2 ng/mL | Standard Deviation 53.4 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Post | 124.8 ng/mL | Standard Deviation 53.1 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Change | -3.12 ng/mL | Standard Deviation 16.2 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGF-1 | Pre | 127.9 ng/mL | Standard Deviation 50.7 |
Comparison: intra-analysis within the weight loss armp-value: 0.294paired t-test
Comparison: intra-analysis within the control armp-value: 0.44paired t-test
Comparison: analysis between the weight loss and control armsp-value: 0.18695% CI: [-4.31, 21.3]paired t-test
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.
Time frame: baseline and post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Pre | 8.78 ng/mL | Standard Deviation 5.87 |
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Post | 10.9 ng/mL | Standard Deviation 5.77 |
| Arm 1: Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Change | 2.19 ng/mL | Standard Deviation 5.95 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Pre | 16.7 ng/mL | Standard Deviation 11.1 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Post | 16.6 ng/mL | Standard Deviation 11.2 |
| Arm 2: No Weight Loss | Change in Serum IGF-related Analytes: IGFBP-1 | Change | -0.03 ng/mL | Standard Deviation 7.43 |
Comparison: intra-analysis within the weight loss armp-value: 0.162paired t-test
Comparison: intra-analysis within the control armp-value: 0.986paired t-test
Comparison: analysis between the weight loss and control armsp-value: 0.35395% CI: [-2.58, 7.02]paired t-test
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.
Time frame: baseline and post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Pre | 92.8 density units | Standard Deviation 25.8 |
| Arm 1: Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Post | 90.8 density units | Standard Deviation 23.4 |
| Arm 1: Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Change | -2.01 density units | Standard Deviation 7.23 |
| Arm 2: No Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Post | 83.5 density units | Standard Deviation 26.9 |
| Arm 2: No Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Change | -1.24 density units | Standard Deviation 12.72 |
| Arm 2: No Weight Loss | Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells | Pre | 84.8 density units | Standard Deviation 27.3 |
Comparison: analysis between the intervention and control armsp-value: 0.83595% CI: [-6.7, 8.24]paired t-test
Comparison: intra-analysis within the weight loss armp-value: 0.283paired t-test
Comparison: intra-analysis within the control armp-value: 0.701paired t-test
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.)
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Weight Loss | Proliferative Index in Prostate Cancer Epithelium Specimen | 6.69 percentage of cells stained | Standard Deviation 5.05 |
| Arm 2: No Weight Loss | Proliferative Index in Prostate Cancer Epithelium Specimen | 5.79 percentage of cells stained | Standard Deviation 3 |
p-value: 0.884Wilcoxon (Mann-Whitney)