The Effects of Calcitriol on Biomarkers in Diabetic Kidney Disease Patients

NCT ID: NCT05298163

Last Updated: 2022-04-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-30

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intervention Group

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.

Group Type EXPERIMENTAL

Calcitriol capsules

Intervention Type 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.

Placebo Group

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.

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type 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

Interventions

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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.

Intervention Type DRUG

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

Intervention Type DRUG

Other Intervention Names

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Oscal

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Indonesia University

OTHER

Sponsor Role lead

Responsible Party

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Pringgodigdo Nugroho, MD

Staff of Nephrology and Hypertension Division, Internal Medicine Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pringgodigdo Nugroho, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Dr. Cipto Mangunkusumo Hospital

Jakarta Pusat, DKI Jakarta, Indonesia

Site Status

Countries

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Indonesia

Central Contacts

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Pringgodigdo Nugroho, MD

Role: CONTACT

+628179822504

Chairina Noor, MD

Role: CONTACT

+6281294630110

Facility Contacts

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Pringgodigdo Nugroho, MD

Role: primary

+628179822504

References

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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.

Reference Type BACKGROUND
PMID: 29486908 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28197499 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30158836 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32232184 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 29852492 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24327929 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32549781 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22615747 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29922234 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22068875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25339703 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23123403 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28848172 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29446731 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32766307 (View on PubMed)

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.

Reference Type DERIVED
PMID: 41145267 (View on PubMed)

Other Identifiers

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KET-176/UN2.F1/ETIK/2022

Identifier Type: -

Identifier Source: org_study_id

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