The Effectiveness and Safety of Calcium Carbonate in Chronic Kidney Disease With Normophosphatemia

Chronic Kidney Diseases Clinical Trial

Official title:

The Effectiveness and Safety of Calcium Carbonate in Chronic Kidney Disease With Normophosphatemia: A Double Blind, Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03550534
• Other study ID #: 198/UN2.F1/ETIK/2015
• Status: Completed
• Phase: N/A
• Start date: November 6, 2015
• Est. completion date: December 11, 2016

Study information

• Verified date: June 2018
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Patient with stage 3 or 4 chronic kidney disease (CKD) usually has normal level of serum phosphate, due to increased serum fibroblast growth factor-23 (FGF23) level that resulted in increased phosphate urine excretion. On the other hand, serum FGF23 elevation was related to CKD progression, vascular calcification, cardiomegaly, and mortality. This double blind, randomized controlled trial study was conducted to evaluate effectiveness and safety of calcium carbonate administration in stage 3 or 4 CKD patients with normophosphatemia.

Hypothesis: Calcium carbonate administration is effective and safe in chronic kidney disease (CKD) with normophosphatemia.

Description:

Cardiovascular disease is the most cause of mortality of chronic kidney disease (CKD) patients. As CKD progresses, the prevalence of cardiovascular disease also increased. Beside traditional cardiovascular risk factor that the investigators have known, some non-traditional cardiovascular risk factors were reported to be associated with cardiovascular disease in CKD patients, which one of them was increased level of fibroblast growth factor-23 (FGF23).[1,2]

FGF23 reduces production of 1,25-vitamin D3 and expression of sodium-phosphate cotransport, and also excretes phosphate through urine. In healthy and CKD population, increased phosphate level resulted in increased production of FGF23. Normophosphatemia state in early to moderate stage of CKD was reported due to body compensation by increasing the level of FGF23. On the other hand, increased serum FGF23 level was related to CKD progression, cardiomegaly, vascular calcification, and mortality.[1] There are several ways to prevent hyperphosphatemia, such as low phosphor intake, phosphate binder administration, and adequate dialysis.[3]

Phosphate binder was reported to give positive effects in CKD patients with hyperphosphatemia. Studies which investigated the use of phosphate binder in CKD patients with normophosphatemia to decrease FGF23 were still limited and the result was controversial.[1]

Therefore, this double blind, randomized controlled trial study investigated the effectiveness and safety of calcium carbonate in early to moderate CKD patients with normophosphatemia in lowering FGF23 levels. Study participant were randomized to receive calcium carbonate or placebo for 12 weeks. Before and after intervention, blood and urine sample were taken to examine serum FGF23, serum phosphate, urine phosphate, ionized calcium, serum calcium, urea, creatinine, estimated glomerular filtration rate (eGFR), and albumin. Effectiveness of calcium carbonate administration was indicated by serum FGF23, while safety was indicated by serum calcium.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 11, 2016
• Est. primary completion date: December 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Stage 3 or 4 chronic kidney disease patient that visit nephrology or endocrinology outpatient clinic of dr. Cipto Mangunkusumo Hospital

• Normal level of serum phosphate

• Agreed to join in this study

Exclusion Criteria:

• Subjects with BMI < 18.5 kg/m2 or > 30 kg/m2

• Consume drugs which may interfere bone mineral metabolism

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Calcium Carbonate
Calcium carbonate was obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.
• Placebo oral capsule
Placebo oral capsule was also obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.

Locations

Country	Name	City	State
Indonesia	dr. Cipto Mangunkusumo Hospital	Jakarta Pusat	DKI Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
Indonesia University	Dr Cipto Mangunkusumo General Hospital

Country where clinical trial is conducted

Indonesia, 

References & Publications (15)

Bayliss G, Weinrauch LA, D'Elia JA. Pathophysiology of obesity-related renal dysfunction contributes to diabetic nephropathy. Curr Diab Rep. 2012 Aug;12(4):440-6. doi: 10.1007/s11892-012-0288-1. Review. — View Citation

Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol. 2012 Aug;23(8):140 — View Citation

Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F; MMKD Study Group, Kuen E, König P, Kraatz G, Mann JF, Müller GA, Köhler H, Riegler P. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disea — View Citation

Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, Peacock M. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int. 2013 May;83(5):959-66. doi: 10.1038/ki.2012.403. Epub 2012 Dec 19. — View Citation

Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M; Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibr — View Citation

Iseki K. Gender differences in chronic kidney disease. Kidney Int. 2008 Aug;74(4):415-7. doi: 10.1038/ki.2008.261. — View Citation

Ketteler M, Leonard M. KDIGO 2016 Clinical practice guideline update on diagnosis, evaluation, prevention, and treatment of CKD-MBD. Off J Int Soc Nephrol. 2016;(August):1-45

Langman CB, Cannata-Andía JB. Calcium in chronic kidney disease: myths and realities. Introduction. Clin J Am Soc Nephrol. 2010 Jan;5 Suppl 1:S1-2. doi: 10.2215/CJN.06140809. — View Citation

Martin K, Floege J, Ketteler M. Bone and mineral metabolism in chronic kidney disease. In: Johnson R, Feehally J, Floege J, editors. Comprehensive clinical nephrology. Fifth edition. Philadelphia: Saunders; 2015. p. 984-7.

Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moysés RM. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010 Feb;5 — View Citation

Perhimpunan Nefrologi Indonesia. 8th Report of Indonesian Renal Registry. Jakarta; 2015

Prakash S, O'Hare AM. Interaction of aging and chronic kidney disease. Semin Nephrol. 2009 Sep;29(5):497-503. doi: 10.1016/j.semnephrol.2009.06.006. — View Citation

Shigematsu T, Negi S; COLC Research Group. Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH (COLC Study). Nephrol Dial Transplant. 2012 Mar;27(3):1050-4. do — View Citation

Soriano S, Ojeda R, Rodríguez M, Almadén Y, Rodríguez M, Martín-Malo A, Aljama P. The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients. Clin Nephrol. 2013 Jul;80(1):17-22. doi: 10.5414/CN10776 — View Citation

Sprague SM, Abboud H, Qiu P, Dauphin M, Zhang P, Finn W. Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial. Clin J Am Soc Nephrol. 2009 Jan;4(1):178-85. doi: 10.2215/CJN.02830608. Epub 2008 Dec 3. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Fibroblast Growth Factor 23 (FGF-23)	Serum FGF23 (pg/ml) as cardiovascular risk factor in chronic kidney disease (CKD) was measured and compared between 2 groups before and after intervention	12 weeks
Secondary	Serum Calcium Level	Serum calcium level (mg/dl) was measured and compared between 2 groups before and after intervention	12 weeks