The Effects of Calcitriol on Biomarkers in Diabetic Kidney Disease Patients

NCT05298163 | Unknown DMC

• 1 other identifier: KET-176/UN2.F1/ETIK/2022
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetic Kidney Disease

Keywords

Diabetic Kidney Disease; Podocin; Nephrin; Calcitriol; Tubular injury; Podocyte injury

Outcome Measures

Primary Outcomes (6)

• Urinary podocin

  Marker of podocyte injury, will be measured before, during, and after treatment

  6 months

• Urinary nephrin

  Marker of podocyte injury, will be measured before, during, and after treatment

  6 months

• Urinary KIM-1

  Marker of tubular injury, will be measured before, during, and after treatment

  6 months

• Urinary IL-6

  Marker of kidney inflammation, will be measured before, during, and after treatment

  6 months

• Plasma renin

  Marker of hemodynamic pathway, will be measured before, during, and after treatment

  6 months

• Albuminuria

  Marker of glomerular damage, will be measured before, during, and after treatment

  6 months

Secondary Outcomes (1)

• Calcium level

  6 months

Study Arms (2)

Intervention Group

EXPERIMENTAL

Drug: Calcitriol The intervention group will be given calcitriol at a dose of 0.25 mcg/day for six months in the form of capsules that have been marked and numbered. The drugs will be taken through the RSCM pharmacy once a month during visit and the allocation will be given using drug labels that are sealed and packaged identically.

Drug: Calcitriol capsules

Placebo Group

ACTIVE COMPARATOR

Drug: Placebo oral The placebo drug will be given for six months in the form of capsules that have been marked and numbered. The drugs will be taken through the RSCM pharmacy once a month during visit and the allocation will be given using drug labels that are sealed and packaged identically.

Drug: Placebo

Interventions

Calcitriol capsules DRUG

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.

Also known as: Oscal

Intervention Group

Placebo DRUG

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

Placebo Group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Dr. Cipto Mangunkusumo Hospital

Jakarta Pusat, DKI Jakarta, 10430, Indonesia

Location

Related Publications (16)

• 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.

  PMID: 29486908 BACKGROUND

• 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.

  PMID: 28197499 BACKGROUND

• 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.

  PMID: 30158836 BACKGROUND

• 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.

  PMID: 32232184 BACKGROUND

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

  PMID: 29852492 BACKGROUND

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  PMID: 24327929 BACKGROUND

• 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.

  PMID: 32549781 BACKGROUND

• 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.

  PMID: 22615747 BACKGROUND

• 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.

  PMID: 29922234 BACKGROUND

• 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.

  PMID: 22068875 BACKGROUND

• Marquez 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.

  PMID: 25339703 BACKGROUND

• 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.

  PMID: 23123403 BACKGROUND

• 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.

  PMID: 28848172 BACKGROUND

• 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.

  PMID: 29446731 BACKGROUND

• 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.

  PMID: 32766307 BACKGROUND

• Nugroho P, Lydia A, Soewondo P, Suhardjono, Timan IS, Harimurti K, Ali Z. Modulation of renal inflammation and tubular injury by calcitriol in patients with early diabetic kidney disease: a randomized controlled trial. Ann Med. 2025 Dec;57(1):2577271. doi: 10.1080/07853890.2025.2577271. Epub 2025 Oct 27.

  PMID: 41145267 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

Calcitriol

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Pringgodigdo Nugroho, MD

  Division of Nephrology Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pringgodigdo Nugroho, MD

CONTACT

+628179822504; pringgodigdo.nugroho@ui.ac.id

Chairina Noor, MD

CONTACT

+6281294630110; chairinaazkyanoor@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff of Nephrology and Hypertension Division, Internal Medicine Department

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 28, 2022
• Study Start: April 1, 2022
• Primary Completion: October 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-03

Locations

ID (1)