Clinical Trial: The Deferasirox-calcium-vitamin D3 Therapy for Postmenopausal Osteoporosis (PMOP)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase 2 Study of Deferasirox-calcium-vitamin D3 to Treat Postmenopausal Osteoporosis (PMOP)

Brief Summary:

In 2006, Weinberg proposed a hypothesis that iron accumulation was a risk factor for osteoporosis. Osteoporosis is a common complication in various diseases, such as hemochromatosis, African hemosiderosis, thalassemia, and sickle cell disease, which all share iron accumulation as a common denominator. Moreover, a 3-year retrospective longitudinal study has shown that iron accumulation was also associated with osteoporosis in healthy adults and especially that it can increase the risk of fractures in postmenopausal women. Based on these observations, iron chelation therapy may have a promising future in the treatment of iron accumulation-related osteoporosis by removing iron from the body.

The purpose of this study is to determine whether the addition of the iron chelator, deferasirox, to standard therapy for postmenopausal osteoporosis, is safe and effective.


Detailed Summary:

Postmenopausal osteoporosis (PMOP) is a systemic bone metabolism disease, characterized by progressive bone loss following menopause and a subsequent increase in fracture risk. Estrogen deficiency as a result of menopause is known to increase bone resorption and accelerate bone loss. Furthermore, postmenopausal women may exhibit iron accumulation, in addition to estrogen deficiency. Elevated iron levels are a risk factor for PMOP in postmenopausal women, and reducing the iron overload by iron chelators has been demonstrated to benefit bone cell metabolism in vitro and improve the bone in vivo by normalizing osteoclastic bone resorption and formation.

Although the safety and efficacy of deferasirox have been evaluated in iron-overloaded patients extensively, there are no data in iron-accumulated postmenopausal women, let alone in iron-accumulated postmenopausal women with osteoporosis. Therefore, at the currently planned dose, confirming safety and efficacy is essential in the current study to lay the groundwork for a future phase III clinical trial.

This is a prospective, phase II, randomized, open label, placebo-controlled study of calcium-vitamin D3 plus deferasirox vs. calcium-vitamin D3 for postmenopausal osteoporosis. Ten postmenopausal women diagnosed with osteoporosis by DXA, who were accompanied by iron accumulation (serum 500ng/ml≤ferritin≤1000ng/ml), will be randomized to receive calcium-vitamin D3 plus deferasirox or calcium-vitamin D3 (n = 5 per arm).

The primary objective is to determine the safety and tolerability of adjunctive deferasirox therapy in postmenopausal women being treated with calcium-vitamin D3 for osteoporosis, and to obtain exploratory data on the efficacy of the iron chelation treatment. The reduction in iron levels with deferasiro
Sponsor: Second Affiliated Hospital of Soochow University

Current Primary Outcome:

  • Number of participants with adverse events [ Time Frame: 12 months ]

    An adverse event was any untoward medical occurrence in participants, and did not necessarily need to have a causal relationship with the drug in the trial. The relationship of each adverse event to study drug or the severity of each adverse event was judged by the investigator, as described below. A serious adverse event is an adverse event occurring at any dose that resulted in any of the following outcomes or actions:

    fatal or life-threatening; requires inpatient hospitalization; persistent or significant disability/incapacity;

  • Number of participants with abnormal blood pressure, heart rate, body temperature, and/or physical examination that are related to the treatment [ Time Frame: 12 months ]
  • Bone mineral density [ Time Frame: Baseline, Month 6, Month 12 ]
    Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. Percent changes in DXA Bone Mineral Density from baseline to month 6 and month 12 of the trial in all patients. Percent change from Baseline was calculated as (BMD at Month 6 or Month 12 - BMD at Baseline)/BMD at Baseline * 100%.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change from baseline in serum C-terminal telopeptide of type I collagen (β-CTX) [ Time Frame: Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  • Change from baseline in serum N-aminoterminal prepeptide of type I procollagen (P1NP) [ Time Frame: Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  • Change from baseline in serum ferritin [ Time Frame: Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  • Change from baseline in blood chemistry [ Time Frame: Baseline, Week 2, Week 4 and Month 3, Month 6, Month 9, Month 12 of the trial ]
  • Change from baseline in hematology [ Time Frame: Baseline, Week 2, Week 4 and Month 3, Month 6, Month 9, Month 12 of the trial ]


Original Secondary Outcome: Same as current

Information By: Second Affiliated Hospital of Soochow University

Dates:
Date Received: July 19, 2016
Date Started: August 2016
Date Completion: March 2018
Last Updated: July 30, 2016
Last Verified: July 2016