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

NCT02854722 | Unknown Phase 2 DMC

• 1 other identifier: BL2014044
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Postmenopausal Osteoporosis

Keywords

deferasirox; iron accumulation

Outcome Measures

Primary Outcomes (3)

• Number of participants with adverse events

  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;

  12 months

• Number of participants with abnormal blood pressure, heart rate, body temperature, and/or physical examination that are related to the treatment

  12 months

• Bone mineral density

  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%.

  Baseline, Month 6, Month 12

Secondary Outcomes (5)

• Change from baseline in serum C-terminal telopeptide of type I collagen (β-CTX)

  Baseline, Month 3, Month 6, Month 9 and Month 12

• Change from baseline in serum N-aminoterminal prepeptide of type I procollagen (P1NP)

  Baseline, Month 3, Month 6, Month 9 and Month 12

• Change from baseline in serum ferritin

  Baseline, Month 3, Month 6, Month 9 and Month 12

• Change from baseline in blood chemistry

  Baseline, Week 2, Week 4 and Month 3, Month 6, Month 9, Month 12 of the trial

• Change from baseline in hematology

  Baseline, Week 2, Week 4 and Month 3, Month 6, Month 9, Month 12 of the trial

Study Arms (2)

Deferasirox and calcium-vitamin D3

EXPERIMENTAL

Deferasirox is an orodispersible tablet and should be taken daily 30 minutes before breakfast, with a dose of 10 mg/Kg/day ± 5 mg/Kg/day during 12 month. Calcium 500 mg and Vitamin D3 800 IU should also be taken daily as a basic therapy.

Drug: Deferasirox and calcium-vitamin D3; Drug: Calcium-vitamin D3

Calcium-vitamin D3

PLACEBO COMPARATOR

Calcium 500 mg and Vitamin D3 800 IU are taken daily as a basic therapy.

Drug: Calcium-vitamin D3

Interventions

Deferasirox and calcium-vitamin D3 DRUG

deferasirox and calcium-vitamin D3 Deferasirox is an orodispersible tablet and should be taken daily 30 minutes before breakfast, with a dose of 10 mg/Kg/day ± 5 mg/Kg/day during 12 month. Calcium 500 mg and vitamin D3 800 IU should also be taken daily as a basic therapy.

Deferasirox and calcium-vitamin D3

Calcium-vitamin D3 DRUG

Calcium 500 mg and vitamin D3 800 IU are taken daily as a basic therapy.

Calcium-vitamin D3; Deferasirox and calcium-vitamin D3

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lumbar spine or hip BMD T-score ≤-2.5 SD.
• Elevated serum ferritin (females: serum 500ng/ml≤ferritin≤1000ng/ml).

You may not qualify if:

• Anemia \< 10 g/dl
• Serum liver enzymes or bilirubin above the upper limit of normal at screening.
• Patients with creatinine clearance \<60 ml/min will be excluded.
• Known allergy or contraindication to the administration of Deferasirox.
• History of blood transfusion during the 6 months prior to study entry.
• Oral iron supplementation within the last 4 weeks of study entry.
• Treatment with phlebotomy within 2 weeks of screening visit.
• Patient is already taking deferasirox therapy for any reason at the time of screening.
• Patients currently or previously treated with deferiprone or Deferasirox.
• Patients with active inflammatory diseases that may interfere with the accurate measurement of serum ferritin.
• Patients with a diagnosis of a clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation.

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead

Study Sites (1)

Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

RECRUITING

Related Publications (9)

• Kim BJ, Ahn SH, Bae SJ, Kim EH, Lee SH, Kim HK, Choe JW, Koh JM, Kim GS. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study. J Bone Miner Res. 2012 Nov;27(11):2279-90. doi: 10.1002/jbmr.1692.

  PMID: 22729843 BACKGROUND

• Mitchell F. Bone: high body iron stores lead to bone loss. Nat Rev Endocrinol. 2012 Sep;8(9):506. doi: 10.1038/nrendo.2012.127. Epub 2012 Jul 17. No abstract available.

  PMID: 22801718 BACKGROUND

• Li GF, Pan YZ, Sirois P, Li K, Xu YJ. Iron homeostasis in osteoporosis and its clinical implications. Osteoporos Int. 2012 Oct;23(10):2403-8. doi: 10.1007/s00198-012-1982-1. Epub 2012 Apr 14.

  PMID: 22525981 BACKGROUND

• Huang X, Xu Y, Partridge NC. Dancing with sex hormones, could iron contribute to the gender difference in osteoporosis? Bone. 2013 Aug;55(2):458-60. doi: 10.1016/j.bone.2013.03.008. Epub 2013 Mar 22. No abstract available.

  PMID: 23523718 BACKGROUND

• Chen B, Yan YL, Liu C, Bo L, Li GF, Wang H, Xu YJ. Therapeutic effect of deferoxamine on iron overload-induced inhibition of osteogenesis in a zebrafish model. Calcif Tissue Int. 2014 Mar;94(3):353-60. doi: 10.1007/s00223-013-9817-4. Epub 2014 Jan 12.

  PMID: 24414856 BACKGROUND

• Chen B, Li GF, Shen Y, Huang XI, Xu YJ. Reducing iron accumulation: A potential approach for the prevention and treatment of postmenopausal osteoporosis. Exp Ther Med. 2015 Jul;10(1):7-11. doi: 10.3892/etm.2015.2484. Epub 2015 May 8.

  PMID: 26170904 BACKGROUND

• Shen GS, Yang Q, Jian JL, Zhao GY, Liu LL, Wang X, Zhang W, Huang X, Xu YJ. Hepcidin1 knockout mice display defects in bone microarchitecture and changes of bone formation markers. Calcif Tissue Int. 2014 Jun;94(6):632-9. doi: 10.1007/s00223-014-9845-8. Epub 2014 Mar 21.

  PMID: 24652331 BACKGROUND

• Xu Y, Li G, Du B, Zhang P, Xiao L, Sirois P, Li K. Hepcidin increases intracellular Ca2+ of osteoblast hFOB1.19 through L-type Ca2+ channels. Regul Pept. 2011 Dec 10;172(1-3):58-61. doi: 10.1016/j.regpep.2011.08.009. Epub 2011 Sep 10.

  PMID: 21911012 BACKGROUND

• Jia P, Xu YJ, Zhang ZL, Li K, Li B, Zhang W, Yang H. Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species. J Orthop Res. 2012 Nov;30(11):1843-52. doi: 10.1002/jor.22133. Epub 2012 May 8.

  PMID: 22570238 BACKGROUND

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• You-Jia Xu, Ph.D,M.D.

  Second Afflilated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

You-Jia Xu, Ph.D,M.D.

CONTACT

+86 512 67783746; xuyoujia@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Science and Education Department

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: August 3, 2016
• Study Start: January 15, 2018
• Primary Completion: June 15, 2019
• Study Completion: June 15, 2020
• Last Updated: May 17, 2018

Record last verified: 2018-05

Locations

CN (1)