Vitamin D Effects on Prostate Pathology - Full Text View

Sponsors and Collaborators:	University of Toronto MOUNT SINAI HOSPITAL University Health Network, Toronto Sunnybrook Health Sciences Centre National Cancer Institute of Canada
Information provided by:	University of Toronto
ClinicalTrials.gov Identifier:	NCT00741364

Purpose

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.

Condition	Intervention	Phase
Prostate Cancer	Dietary Supplement: vitamin D3 (cholecalciferol)	Phase II

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Vitamin D Ergocalciferol Cholecalciferol Ethanol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Efficacy Study
Official Title:	Randomized Trial of the Effects of Vitamin D on Prostate Cancer-Associated Lesions and on Vitamin D Metabolites in Prostate

Further study details as provided by University of Toronto:

Primary Outcome Measures:

immunohistochemical markers of prostate pathology [ Time Frame: end-of-study ] [ Designated as safety issue: No ]
intraprostate vitamin D metabolites [ Time Frame: end-of-study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

calcium (serum and urine) [ Time Frame: biweekly ] [ Designated as safety issue: Yes ]
parathyroid hormone (PTH) [ Time Frame: baseline, final ] [ Designated as safety issue: No ]
prostate specific antigen (PSA) [ Time Frame: baseline, final ] [ Designated as safety issue: No ]
creatinine (serum and urine) [ Time Frame: biweekly ] [ Designated as safety issue: Yes ]
phosphate (serum) [ Time Frame: biweekly ] [ Designated as safety issue: Yes ]
serum vitamin D metabolites [ Time Frame: baseline, final ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	September 2008
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator vitamin D3 (400 IU/d)	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
2: Active Comparator vitamin D3 (10,000 IU/d)	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
3: Active Comparator vitamin D3 (40,000 IU/d)	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

Detailed 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.

Eligibility

Ages Eligible for Study:	30 Years to 85 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741364

Contacts

Contact: Reinhold Vieth, PhD	416-586-5920	rvieth@mtsinai.on.ca
Contact: Dennis Wagner, MSc	416-586-4800 ext 2726	dennis.wagner@utoronto.ca

Locations

Canada, Ontario
University Health Network	Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Karen Hersey, RN 416-946-2155 Karen.Hersey@uhn.on.ca
Principal Investigator: Neil Fleshner, MD, MPH, FRCSC

Sponsors and Collaborators

University of Toronto

MOUNT SINAI HOSPITAL

University Health Network, Toronto

Sunnybrook Health Sciences Centre

National Cancer Institute of Canada

Investigators

Principal Investigator:	Reinhold Vieth, PhD	University of Toronto, Mount Sinai Hospital
Study Director:	Dennis Wagner, MSc	University of Toronto, Mount Sinai Hospital
Principal Investigator:	Theo van der Kwast, MD, PhD, FRCPC	University Health Network, Toronto
Principal Investigator:	Neil Fleshner, MD, MPH, FRCSC	University Health Network, Toronto
Principal Investigator:	Laurence Klotz, MD, FRCSC	Sunnybrook Health Sciences Centre

More Information

Responsible Party:	Mount Sinai Hospital ( Dr. Reinhold Vieth )
Study ID Numbers:	M2140
Study First Received:	August 25, 2008
Last Updated:	October 7, 2008
ClinicalTrials.gov Identifier:	NCT00741364
Health Authority:	Canada: Health Canada

Keywords provided by University of Toronto:

vitamin D
prostate cancer
prostatectomy
pathology
immunohistochemistry

Study placed in the following topic categories:

Cholecalciferol
Vitamin D
Prostatic Diseases
Genital Neoplasms, Male
Ergocalciferols

Urogenital Neoplasms
Genital Diseases, Male
Prostatic Neoplasms
Ethanol

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Growth Substances
Vitamins

Physiological Effects of Drugs
Bone Density Conservation Agents
Micronutrients
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009