Prevention of Micro-architectural Bone Decay in Males With Non-metastatic Prostate Cancer Receiving Androgen Deprivation Therapy (ADT)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Less than 20% of men in whom prostate cancer is diagnosed early die from it. Cardiovascular
      disease is the most common cause of death in men with early prostate cancer. A commonly used
      form of treatment for prostate cancer is androgen deprivation therapy (ADT). ADT, while
      effective for the treatment of prostate cancer, has been linked to undesirable side effects,
      such as an increased risk of bone fractures and diabetes. Bisphosphonates, a class of drugs
      that prevent bone resorption, have been show to reduce the loss of bone mineral density that
      occurs as a consequence of ADT, but the effects of bisphosphonates on preservation of bone
      architecture is unknown.

      This project has two main goals:

      To assess prospectively, in men with prostate cancer receiving ADT, the effect of:

        1. the intravenous bisphosphonate zoledronic acidon ADT-induced microarchitectural decay of
           bone structure.

        2. ADT on insulin resistance and glucose metabolism. We will recruit 100 ambulatory men
           with non-metastatic prostate cancer who are about to commence a three year course of ADT
           as per routine clinical practice at Austin Health. Men will be randomised to receive
           either intravenous zoledronic acid (Aclasta, Novartis Pharmaceuticals) or placebo at
           baseline and after 12 months of ADT. Men with contraindications to zoledronic acid will
           be excluded from the study. All 100 study subjects will have clinical and laboratory
           assessment at baseline, and at 3, 6, 12, 18 and 24 months (study end), and imaging
           studies at baseline and at 6, 12 and 24 months.

      The study protocol is outlined in more detail below (Please see flow chart included in the in

      PICF):

      Clinical and laboratory assessment:

      Full medical history, physical examination and quality of life assessment using the SF-36
      questionnaire. Laboratory studies will include: oral glucose tolerance test (3, 12 and 24
      months Commercial-in-Confidence only) and measurements of measure total testosterone, fasting
      glucose, C-peptide, HBA1c, bone turnover markers.

      Imaging studies:

        1. Bony micro-architecture by high resolution quantitative computed tomography

        2. Bone mineral density and body composition by DEXA This project will have no direct
           benefit for the subjects involved in this study; however, it will improve our
           understanding on the effect of zoledronic acid on bone microarchitecture in men with
           prostate cancer receiving ADT. It will also help us to better understand the effect of
           ADT on insulin resistance and glucose metabolism.
    

Detailed description: 
      Not desired
    

Intervention name(s): Zoledronic acid; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): yearly infusion; yearly infusion
Intervention MeSH terms: Zoledronic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Prostate Cancer; Androgen deprivation; Bone Health; Insulin resistance; Men with nonmetastatic prostate cancer receiving androgen deprivation