Vitamin D Effects on Prostate Pathology

Prostate Cancer Clinical Trial

— DProstate  

Official title:

Randomized Trial of the Effects of Vitamin D on Prostate Cancer-associated Lesions and on Vitamin D Metabolites in Prostate

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00741364
• Other study ID #: M2140
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 25, 2008
• Last updated: September 29, 2011
• Start date: September 2008
• Est. completion date: July 2012

Study information

• Verified date: September 2011
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

There is much interest in understanding the role that vitamin D3 (cholecalciferol) plays in various cancers, and in the prognosis of various cancers once they are discovered. The purpose of this study is to examine the effects of vitamin D on prostate cancer-associated lesions and on vitamin D metabolites in prostate tissue. We will give vitamin D3 to men when they are scheduled to have their prostate removed because of cancer. The men will take vitamin D at one of 3 doses for 4-6 weeks, until the surgery is performed. We will compare the prostate tissue taken from the men receiving the higher doses of vitamin D to tissue from men assigned to the lower doses. We expect to find that the prostate removed at surgery from men who received the high-dose vitamin D treatment will appear more normal, and less cancer like. In addition, we will measure vitamin D metabolites in the prostate to confirm that these did accumulate in the prostate to bring about the effects observed.

Description:

Epidemiologic, laboratory, and clinical reports all suggest that vitamin D3 (cholecalciferol) plays a desirable role in the prevention and prognosis of prostate and other cancers. Prostate cancer cells possess both of the enzymes required to convert vitamin D to the active paracrine hormone, calcitriol. However, the dose-response relationship between serum levels of calcidiol (vitamin D status) and prostate tissue levels of calcidiol and calcitriol is yet to be defined. As a neoadjuvant, prior to radical prostatectomy (for 4-6 wk) vitamin D3 [400 IU (control group), 10,000 IU or 40,000 IU/day] will be given to 90 men randomized, double-blinded, 30 per dose. Immediately after surgery, the pathologist will obtain a few grams of prostate tissue, some of which will be used to assay calcidiol and calcitriol within prostate. From the embedded prostate, we will prepare immunohistochemically stained sections to characterize cellular responses and morphological changes. Our hypothesis is that vitamin D will increase intraprostate calcitriol concentration and thereby lower cellular proliferation (as judged by the markers MIB-1 and p27) in zones of Gleason pattern 3 prostate cancer and in pre-cancerous (PIN) lesions. We expect that our results will provide surrogate outcomes to justify larger trials of vitamin D for treatment of prostate cancer. This research has the potential to: 1. Provide direct evidence at the cellular level using clinical samples that vitamin D lowers cellular proliferation in prostate cancer, 2. Provide guidance about the serum calcidiol concentrations (and thereby vitamin D doses) that should be targeted for such studies, and 3. Eventually support other research directed at vitamin D as a primary prevention strategy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: July 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 30 Years to 85 Years

Eligibility

Inclusion Criteria:

• Diagnosis of a Gleason score 6 or 7 adenocarcinoma of the prostate biopsy

• Patient has elected to have a radical prostatectomy

• Patient is determined fit for surgery

• Normal renal and hepatic function

• Normal serum and urine calcium values

• Normal serum phosphate values

• Normal serum parathyroid hormone values

• Signed written informed consent

Exclusion Criteria:

• Prior use of neoadjuvant androgen deprivation therapy

• Prior use of 5 alpha reductase inhibitors (finasteride or dutasteride) in last 12 months

• Previous or concomitant anti-cancer therapy (chemotherapy, radiotherapy)

• Gleason score 8-10 adenocarcinoma as a biopsy diagnosis

• History of hypercalcemia/hypercalciuria

• History of renal disease

• History of sarcoidosis

• Vitamin D (cholecalciferol) supplement > 1000 IU/day

• Inability to comply with a study protocol

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Dietary Supplement:
• vitamin D3 (cholecalciferol)
liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (5)

Lead Sponsor	Collaborator
University of Toronto	Canadian Cancer Society Research Institute (CCSRI), Mount Sinai Hospital, Canada, Sunnybrook Health Sciences Centre, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	immunohistochemical markers of prostate pathology		end-of-study	No
Primary	intraprostate vitamin D metabolites		end-of-study	No
Secondary	calcium (serum and urine)		biweekly	Yes
Secondary	parathyroid hormone (PTH)		baseline, final	No
Secondary	prostate specific antigen (PSA)		baseline, final	No
Secondary	creatinine (serum and urine)		biweekly	Yes
Secondary	phosphate (serum)		biweekly	Yes
Secondary	serum vitamin D metabolites		baseline, final	No