The Effects of Calcitriol on Biomarkers in Diabetic Kidney Disease Patients

Diabetic Kidney Disease Clinical Trial

Official title:

Effects of Calcitriol on Podocytes in Diabetic Kidney Disease Patients: Assessment of Urine Podocin, Urine Nephrin, Urine Interleukin-6, Urine KIM-1, Plasma Renin, and Albuminuria

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05298163
• Other study ID #: KET-176/UN2.F1/ETIK/2022
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2022
• Est. completion date: December 2022

Study information

• Verified date: March 2022
• Source: Indonesia University
• Contact: Pringgodigdo Nugroho, MD
• Phone: +628179822504
• Email: pringgodigdo.nugroho[@]ui.ac.id
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetic Kidney Disease (DKD) is a complication that occurs due to poor glycemic control over a long period. The decrease or loss of podocytes is an important index in determining the degree of glomerular damage. Previous studies in patients with DKD reported that vitamin D administration can improve their renal function through several mechanisms. However, there is still little evidence available regarding the effects of calcitriol on biomarkers of DKD. This trial is a double-blind randomized controlled trial to assess the effect of calcitriol in DKD patients through several biomarkers which reflect pathomechanism in DKD. Those biomarkers include urinary podocin, urinary nephrin, urinary KIM-1, urinary IL-6, plasma renin, and albuminuria.

The primary outcome is any improvement on podocyte markers, tubular markers, kidney inflammation parameters, plasma renin, and albuminuria between calcitriol and placebo groups. Secondary outcomes include the relation between each marker and the side effects of intervention therapy.

Description:

Diabetic Kidney Disease (DKD) is a complication that occurs due to poor glycemic control over a long period. The decrease or loss of podocytes is an important index in determining the degree of glomerular damage. Albuminuria and estimated glomerular filtration rate (eGFR) are currently used as the marker of DKD. However, these markers may not directly measure renal tissue injury. Thus, investigating novel biomarkers, particularly podocyte-associated biomarkers, is needed to predict DKD. Previous studies in patients with DKD reported that vitamin D administration can improve their renal function. of the various types of vitamin D, there is still little evidence available regarding the effects of calcitriol on biomarkers of DKD. Therefore, this study aimed to determine the effect of calcitriol on podocyte damage markers, tubular injury markers, kidney inflammation parameter, plasma renin, dan albuminuria in DKD patients.

This study is a double-blind randomized controlled clinical trial to assess the effect of calcitriol in DKD patients through several markers including albuminuria. Podocyte damage is characterized by urinary podocin and urinary nephrin, tubular marker injury is characterized by urinary KIM-1, kidney inflammation is represented by urinary IL-6, hemodynamic is represented by plasma renin.

The primary outcome is any improvement on those markers between calcitriol and placebo groups. And the secondary outcomes include the relation between each marker and the side effects of intervention therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 2022
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Controlled type 2 diabetes mellitus with HbA1C at least <8% and albuminuria (UACR>30 mg/mmol)

• Estimated Glomerular Filtration Rate (eGFR) >45 ml/min/1.73 m2

• Agree to participate in the research

Exclusion Criteria:

• Uncontrolled hypertension with routine Angiotensin-converting-enzyme inhibitors (ACEi) or Angiotensin II receptor blockers (ARBs) treatment

• Hypercalcemia (total serum Ca level >10/5 mg/dL)

• Hyperphosphatemia (total serum phosphate level >5 mg/dL)

• Hypersensitivity to calcitriol

• Suffering from other diseases that cause proteinuria

• Acute diseases

• Smoker or previous smoking history

• Taking medications or suplements that can affect calcitriol metabolism (thiazide, digoxin, anti-convulsant)

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• Calcitriol capsules
Calcitriol under the name of Oscal, 0.25 mcg/day (minimum dose) will be given for 6 months, starting at the day of the time when inclusion criteria have been met.
• Placebo
One placebo capsule matching the active drug will be given per day for 6 months, starting at the day of the time when inclusion criteria have been met

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (15)

Garg P. A Review of Podocyte Biology. Am J Nephrol. 2018;47 Suppl 1:3-13. doi: 10.1159/000481633. Epub 2018 May 31. Review. — View Citation

Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2015 Oct 9;5(1):49-56. eCollection 2016. Review. — View Citation

Guo J, Lu C, Zhang F, Yu H, Zhou M, He M, Wang C, Zhao Z, Liu Z. VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway. Cell Physiol Biochem. 2017;43(1):39-51. doi: 10.1159/000480315. Epub 2017 Aug 24. Erratum in: Cell Physiol Biochem. 2020;54(4):799. Cell Physiol Biochem. 2020;54(5):1091. — View Citation

Jim B, Ghanta M, Qipo A, Fan Y, Chuang PY, Cohen HW, Abadi M, Thomas DB, He JC. Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: a cross sectional study. PLoS One. 2012;7(5):e36041. doi: 10.1371/journal.pone.0036041. Epub 2012 May 17. — View Citation

Kostovska I, Tosheska-Trajkovska K, Topuzovska S, Cekovska S, Spasovski G, Kostovski O, Labudovic D. Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria. J Med Biochem. 2020 Jan 10;39(1):83-90. doi: 10.2478/jomb-2019-0026. — View Citation

Kravets I, Mallipattu SK. The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease. J Endocr Soc. 2020 Mar 5;4(4):bvaa029. doi: 10.1210/jendso/bvaa029. eCollection 2020 Apr 1. Review. — View Citation

Lei M, Liu Z, Guo J. The Emerging Role of Vitamin D and Vitamin D Receptor in Diabetic Nephropathy. Biomed Res Int. 2020 Jul 11;2020:4137268. doi: 10.1155/2020/4137268. eCollection 2020. Review. — View Citation

Lin YC, Chang YH, Yang SY, Wu KD, Chu TS. Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc. 2018 Aug;117(8):662-675. doi: 10.1016/j.jfma.2018.02.007. Epub 2018 Mar 2. Review. — View Citation

Márquez E, Riera M, Pascual J, Soler MJ. Renin-angiotensin system within the diabetic podocyte. Am J Physiol Renal Physiol. 2015 Jan 1;308(1):F1-10. doi: 10.1152/ajprenal.00531.2013. Epub 2014 Oct 22. Review. — View Citation

Martin CE, Jones N. Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond. Front Endocrinol (Lausanne). 2018 Jun 5;9:302. doi: 10.3389/fendo.2018.00302. eCollection 2018. Review. — View Citation

Sekulic M, Pichler Sekulic S. A compendium of urinary biomarkers indicative of glomerular podocytopathy. Patholog Res Int. 2013;2013:782395. doi: 10.1155/2013/782395. Epub 2013 Nov 13. Review. — View Citation

Wang Y, Deb DK, Zhang Z, Sun T, Liu W, Yoon D, Kong J, Chen Y, Chang A, Li YC. Vitamin D receptor signaling in podocytes protects against diabetic nephropathy. J Am Soc Nephrol. 2012 Dec;23(12):1977-86. doi: 10.1681/ASN.2012040383. Epub 2012 Nov 2. — View Citation

Yang S, Li A, Wang J, Liu J, Han Y, Zhang W, Li YC, Zhang H. Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases. Curr Med Chem. 2018;25(27):3256-3271. doi: 10.2174/0929867325666180214122352. Review. — View Citation

Zhang W, Wang W, Yu H, Zhang Y, Dai Y, Ning C, Tao L, Sun H, Kellems RE, Blackburn MR, Xia Y. Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage. Hypertension. 2012 Jan;59(1):136-44. doi: 10.1161/HYPERTENSIONAHA.111.173328. Epub 2011 Nov 7. — View Citation

Zylka A, Dumnicka P, Kusnierz-Cabala B, Gala-Bladzinska A, Ceranowicz P, Kucharz J, Zabek-Adamska A, Maziarz B, Drozdz R, Kuzniewski M. Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients. Mediators Inflamm. 2018 Aug 9;2018:7659243. doi: 10.1155/2018/7659243. eCollection 2018. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary podocin	Marker of podocyte injury, will be measured before, during, and after treatment	6 months
Primary	Urinary nephrin	Marker of podocyte injury, will be measured before, during, and after treatment	6 months
Primary	Urinary KIM-1	Marker of tubular injury, will be measured before, during, and after treatment	6 months
Primary	Urinary IL-6	Marker of kidney inflammation, will be measured before, during, and after treatment	6 months
Primary	Plasma renin	Marker of hemodynamic pathway, will be measured before, during, and after treatment	6 months
Primary	Albuminuria	Marker of glomerular damage, will be measured before, during, and after treatment	6 months
Secondary	Calcium level	Will be measured monthly	6 months