Vitamin D3 Supplementation for Low-Risk Prostate Cancer: A Randomized Trial
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Prostate Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 19 - 90 |
| Updated: | 1/13/2019 |
| Start Date: | January 3, 2013 |
| End Date: | December 31, 2019 |
Vitamin D promotes the differentiation of prostate cancer cells and maintains the
differentiated phenotype of prostate epithelial cells. The results of the investigators'
clinical studies indicate that vitamin D3 supplementation results in a decrease of positive
cancer cores at repeat biopsy in subjects with low-risk prostate cancer. The investigators
hypothesize that Veterans who have early-stage prostate cancer and who take vitamin D3 at
4000 international units per day (intervention group) will show an improvement in the number
of positive cores and in Gleason score at repeat biopsy, and a decreased likelihood of
undergoing definitive treatment (prostatectomy or radiation therapy), compared to Veteran
subjects taking placebo (control group).
differentiated phenotype of prostate epithelial cells. The results of the investigators'
clinical studies indicate that vitamin D3 supplementation results in a decrease of positive
cancer cores at repeat biopsy in subjects with low-risk prostate cancer. The investigators
hypothesize that Veterans who have early-stage prostate cancer and who take vitamin D3 at
4000 international units per day (intervention group) will show an improvement in the number
of positive cores and in Gleason score at repeat biopsy, and a decreased likelihood of
undergoing definitive treatment (prostatectomy or radiation therapy), compared to Veteran
subjects taking placebo (control group).
The central hypothesis of this grant application is that vitamin D3 (cholecalciferol)
supplementation will benefit Veteran subjects diagnosed with early-stage, low-risk prostate
cancer, who elect to have their disease monitored through active surveillance. Specifically,
the investigators hypothesize that Veterans who take vitamin D3 at a daily dose of 4000
international units (IU) for a minimum of one year (intervention group) will show an
improvement in the number of positive cores and in Gleason score at repeat biopsy, and a
decreased likelihood of undergoing additional treatment (hormone therapy, prostatectomy or
radiation therapy), compared to Veterans taking placebo (control group).
To test this hypothesis, the investigators propose the following Specific Aims:
1. To determine whether vitamin D3 (4,000 IU per day FOR AT LEAST ONE YEAR) will result in
a significant improvement of the pathology status at repeat biopsy in Veteran subjects
taking vitamin D3, compared to Veteran subjects taking placebo. This hypothesis will be
tested through a randomized clinical trial, which will enroll 136 Veteran subjects (68
participants per arm), diagnosed with early-stage prostate cancer (Gleason score 6, PSA
10, clinical stage T1C or T2a). The pathology status will be measured by the change in
Gleason score and the number of positive cores in prostate needle biopsy specimens
between baseline and the end of the study. Pre- and post-study biopsies will be
performed as part of the standard medical care for diagnosis and active surveillance.
2. To determine whether vitamin D3 supplementation, compared to placebo, will result in a
significant decrease in the number of Veteran subjects who will undergo additional
treatment (hormone therapy, prostatectomy or radiation therapy), following the outcome
of repeat biopsy.
3. To analyze changes in the serum levels of cholecalciferol, 25(OH)D, 1,25(OH)2D, and
prostate-specific antigen (PSA) at baseline and at the end of the study, and to estimate
the associations between changes in these measures and pathology outcomes (Gleason score
and number of positive cores).
4. To compare the expression of molecular biomarkers, which are prognostically relevant to
prostate cancer progression, in pre- and post- treatment biopsy tissue specimens.
Paraffin-embedded sections will be processed to assess by immunohistochemical techniques
the expression of the following biomarkers: Vitamin D Receptor (VDR), P21, Tumor Growth
Factor (TGF ), Cyclooxygenase 2 (COX-2), and NF B. All of these protein products impact
growth control and chronic inflammation in prostate cancer progression and are
specifically affected by Vitamin D status.
Implementation of the proposed studies would demonstrate that Vitamin D3 supplementation
provides a welcome addition to active surveillance, since patients who respond to Vitamin D3
supplementation (as indicated by a decrease in score or number of positive cores at repeat
biopsy) can safely continue active surveillance and would not need definitive treatment. In
turn, this would result in a decreased likelihood of overtreatment. On the other hand,
subjects who progress after Vitamin D3 supplementation, as indicated by an increase in
Gleason score or number of positive cores at repeat biopsy, may have more aggressive disease
and may need to consider definitive treatment. Therefore, both groups of patients (responders
as well as non-responders) would benefit from Vitamin D3 supplementation, an intervention
strategy that is extremely cost-effective and easy to implement.
supplementation will benefit Veteran subjects diagnosed with early-stage, low-risk prostate
cancer, who elect to have their disease monitored through active surveillance. Specifically,
the investigators hypothesize that Veterans who take vitamin D3 at a daily dose of 4000
international units (IU) for a minimum of one year (intervention group) will show an
improvement in the number of positive cores and in Gleason score at repeat biopsy, and a
decreased likelihood of undergoing additional treatment (hormone therapy, prostatectomy or
radiation therapy), compared to Veterans taking placebo (control group).
To test this hypothesis, the investigators propose the following Specific Aims:
1. To determine whether vitamin D3 (4,000 IU per day FOR AT LEAST ONE YEAR) will result in
a significant improvement of the pathology status at repeat biopsy in Veteran subjects
taking vitamin D3, compared to Veteran subjects taking placebo. This hypothesis will be
tested through a randomized clinical trial, which will enroll 136 Veteran subjects (68
participants per arm), diagnosed with early-stage prostate cancer (Gleason score 6, PSA
10, clinical stage T1C or T2a). The pathology status will be measured by the change in
Gleason score and the number of positive cores in prostate needle biopsy specimens
between baseline and the end of the study. Pre- and post-study biopsies will be
performed as part of the standard medical care for diagnosis and active surveillance.
2. To determine whether vitamin D3 supplementation, compared to placebo, will result in a
significant decrease in the number of Veteran subjects who will undergo additional
treatment (hormone therapy, prostatectomy or radiation therapy), following the outcome
of repeat biopsy.
3. To analyze changes in the serum levels of cholecalciferol, 25(OH)D, 1,25(OH)2D, and
prostate-specific antigen (PSA) at baseline and at the end of the study, and to estimate
the associations between changes in these measures and pathology outcomes (Gleason score
and number of positive cores).
4. To compare the expression of molecular biomarkers, which are prognostically relevant to
prostate cancer progression, in pre- and post- treatment biopsy tissue specimens.
Paraffin-embedded sections will be processed to assess by immunohistochemical techniques
the expression of the following biomarkers: Vitamin D Receptor (VDR), P21, Tumor Growth
Factor (TGF ), Cyclooxygenase 2 (COX-2), and NF B. All of these protein products impact
growth control and chronic inflammation in prostate cancer progression and are
specifically affected by Vitamin D status.
Implementation of the proposed studies would demonstrate that Vitamin D3 supplementation
provides a welcome addition to active surveillance, since patients who respond to Vitamin D3
supplementation (as indicated by a decrease in score or number of positive cores at repeat
biopsy) can safely continue active surveillance and would not need definitive treatment. In
turn, this would result in a decreased likelihood of overtreatment. On the other hand,
subjects who progress after Vitamin D3 supplementation, as indicated by an increase in
Gleason score or number of positive cores at repeat biopsy, may have more aggressive disease
and may need to consider definitive treatment. Therefore, both groups of patients (responders
as well as non-responders) would benefit from Vitamin D3 supplementation, an intervention
strategy that is extremely cost-effective and easy to implement.
Inclusion Criteria:
- Male 19 - 90 years old - Low-grade prostate cancer
- Clinical Stage T1C or T2a
- Serum PSA < 10.0 ng/ml
- Gleason Score < or = to 6 (either architectural pattern < or = to 3)
- Decision to monitor prostate cancer in Active Surveillance
- Serum creatinine < 2.0 mg/dL
- Serum phosphorus > 2.3 and < 4.8 mg/dL
- Serum calcium > 8.5 and < 10.5 mg/dL
- Must be capable of giving consent to participate in the study
Exclusion Criteria:
- Any concurrent malignancy, except non-melanoma skin cancer
- History of sarcoidosis
- History of Primary Hyperparathyroidism
- History of hypercalcemia
- Vitamin D supplementation > 2,000 IU daily
- Lithium medication
We found this trial at
2
sites
171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Phone: 843-792-8303
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Charleston, South Carolina 29401
Principal Investigator: Sebastiano Gattoni-Celli, MD
Phone: 843-789-6707
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