Bone Markers and Bone Density Changes in Hyperperparathyroid Dialysis Patients Under Cinacalcet Treatment

NCT04637360 | Completed DMC

• 1 other identifier: MSIRB2018004
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic kidney disease related mineral and bone disorders (CKD-MBDs) and secondary hyperparathyroidism (SHPT) are observed in most patients with chronic kidney disease on dialysis (CKD-5D). The original use of the calcimimetic cinacalcet in these patients was to reduce the elevated parathyroid hormone (PTH) levels; however, subsequent clinical studies consistently confirmed its beneficial effects on mineral disturbances and bone disease. Although many mechanisms proposed, its specific mechanisms underlying the bone disease is still unclear. Recently, Wnt signaling and their inhibitors were proposed to involve in fine control of osteoclast-to-osteoblast cross-talk. In previous study, investigators explore the changes in Wnt 10b in bone microenvironment after addition of calcimimetic cinacalcet using in vitro osteoclasts. In vitro results were confirmed in 5/6 nephrectomy mice, which were grouped into control, with cinacalcet and without cinacalcet groups. From in-vitro study, investigators found cinacalcet increase mineralization; enhance osteoclast apoptosis, which probably work as osteoclast-osteoblast cross talk for bone formation. Similar results were found in-vivo animal study, and the micro-CT of cinacalcet treated CKD animals revealed a significantly decrease in cortical porosity. On the basis of our in-vitro and animal study, investigators propose that cinacalcet have definitive role on bone turnover marker and bone density changes among SHPT dialysis patients. Methods: Our study includes 50 hyperparathyroid dialysis patients using cinacalcet from 1st Dec 2017 to 31 Oct 2018. Investigators will exclude post-menopausal female subjects. Enzyme-linked immunosorbent assay and Western blot analysis will be done for bone turnover markers (TRACP，Alk-P，S1P，BMP6，Wnt，10B，16，SOST，P1NP，PDGF BB，HGF and CTHRC1, etc.). Bone mineral density will be determined by dual-energy X-ray absorptiometry (DXA). Plasma fibroblast growth factor (FGF-23), Ca 2+ , P 3+ , calcium-phosphorus product and parathyroid hormone will also be measured. Data will be collected and analyzed the differences between baseline measures and 4 weekly and follow up for 6 months after the treatment. Control group that we enrolled 30 hyperparathyroid dialysis patients using traditional therapy active vitamin D without use cinacalcet.

Conditions

Hyperparathyroidism; Secondary, Renal

Keywords

clastokines; hemodialysis; hyperparathyroidism; osteoporosis

Outcome Measures

Primary Outcomes (1)

• Parathyroid serum level

  lower in serum intact parathyroid serum level (iPTH\<300 pg/mL) with 6 months cinacalcet treatment.

  After treatment for 6 months.

Secondary Outcomes (1)

• Bone mineral density

  After treatment for 6 months.

Study Arms (2)

Cinacalcet treatment

EXPERIMENTAL

hyperparathyroid dialysis patients using cinacalcet and active vitamin D for 6 months

Drug: Cinacalcet Tablets; Drug: calcitriol

traditional therapy active vitamin D

EXPERIMENTAL

hyperparathyroid dialysis patients using traditional therapy active vitamin D without use cinacalcet for 6 months.

Drug: calcitriol

Interventions

Cinacalcet Tablets DRUG

All study subjects were treated with a fixed dose of oral Cinacalcet (25 mg/day) from baseline to 6 months.

Also known as: CINACA®, Anxo, Taiwan

Cinacalcet treatment

calcitriol DRUG

All hyperparathyroidism were treated as traditional therapy with oral calcitriol 0.25 mcg(dosage according to IPTH serum level) from baseline to 6 months.

Also known as: Macalol Cap 0.25mcg

Cinacalcet treatment; traditional therapy active vitamin D

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• yrs of age and eligible for consent
• Hyperparathyroid (iPTH\>300 pg/mL) regular dialysis patients using cinacalcet and start the treatment during the study period.

You may not qualify if:

• \<20yrs or \>80yrs patients
• Post-menopausal female patients
• Malignancies, inflammatory or infectious disease \< 3 months
• Pregnancy
• Severe malnutrition
• Surgical intervention \< 3 months
• Acute myocardial infarction, unstable angina, cerebrovascular disease or transient ischemic attack, deep vein thrombosis, pulmonary embolism, congestive heart failure \< 3months.

Sponsors & Collaborators

• Min-Sheng General Hospital: lead
• Taipei Medical University Shuang Ho Hospital: collaborator
• Taipei Medical University: collaborator
• En Chu Kong Hospital: collaborator
• National Taiwan University: collaborator
• Taichung Tzu Chi Hospital: collaborator

Study Sites (1)

Min sheng general hospital

Taoyuan, Taiwan

Location

Related Publications (7)

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.

  PMID: 19644521 BACKGROUND

• London GM, Marchais SJ, Guerin AP, Boutouyrie P, Metivier F, de Vernejoul MC. Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol. 2008 Sep;19(9):1827-35. doi: 10.1681/ASN.2007050622. Epub 2008 May 14.

  PMID: 18480316 BACKGROUND

• Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011 Apr;6(4):913-21. doi: 10.2215/CJN.06040710. Epub 2011 Mar 31.

  PMID: 21454719 BACKGROUND

• Westin G, Bjorklund P, Akerstrom G. Molecular genetics of parathyroid disease. World J Surg. 2009 Nov;33(11):2224-33. doi: 10.1007/s00268-009-0022-6.

  PMID: 19373510 BACKGROUND

• Zheng CM, Zheng JQ, Wu CC, Lu CL, Shyu JF, Yung-Ho H, Wu MY, Chiu IJ, Wang YH, Lin YF, Lu KC. Bone loss in chronic kidney disease: Quantity or quality? Bone. 2016 Jun;87:57-70. doi: 10.1016/j.bone.2016.03.017. Epub 2016 Apr 2.

  PMID: 27049042 BACKGROUND

• Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004 Aug;15(8):2208-18. doi: 10.1097/01.ASN.0000133041.27682.A2.

  PMID: 15284307 RESULT

• Mazzaferro S, Tartaglione L, Rotondi S, Bover J, Goldsmith D, Pasquali M. News on biomarkers in CKD-MBD. Semin Nephrol. 2014 Nov;34(6):598-611. doi: 10.1016/j.semnephrol.2014.09.006.

  PMID: 25498379 RESULT

MeSH Terms

Conditions

Hyperparathyroidism; Neoplasm Metastasis; Osteoporosis

Interventions

Cinacalcet; Calcitriol

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Ren-Si Syu, Dr.

  Min-Sheng General Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 19, 2020
• Study Start: January 1, 2018
• Primary Completion: December 31, 2018
• Study Completion: June 30, 2020
• Last Updated: November 19, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)