Effect of Glucocorticoids on Inflammation and Bone Metabolism in Patients With Glomerular Disease

Effect of High-dose Glucocorticoids on Markers of Inflammation and Bone Metabolism in Patients With Primary Glomerular Disease

The aim of the study is to assess the influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease. The study would include 40 patients with chronic kidney disease. The main inclusion criterion is clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24h. The exclusion criteria include secondary glomerular disease, acute kidney injury, acute or chronic inflammation, history of non-compliance.

Study Overview

• Status: Recruiting
• Conditions: Glomerular Disease
• Intervention / Treatment: Drug: Methylprednisolone, prednisone

Detailed Description

Glucocorticoids are one of the most widely used classes of drugs to treat inflammatory and autoimmune diseases. They increase formation of osteoclasts and enhance bone resorption thereby increasing risk of bone fractures and osteoporosis.

Sirtuin-1(SIRT-1) belongs to family of proteins involved in protection against inflammation and oxidative stress. A role of SIRT-1 in regulation of bone metabolism during high-dose steroid therapy is unknown.

The study protocol was approved by the local Bioethics Committee and the study is conducted according to the Declaration of Helsinki. Adult patients with the previous diagnosed primary glomerular disease based on both clinical and renal biopsy findings are included.

Plasma concentration of SIRT-1, interleukin-6 (IL-6), fibroblast growth factor 23 (FGF-23), sclerostin, calcium, phosphate, parathormone (PTH) and urine excretion of total protein, albumin, creatinine, calcium and phosphate are measured at baseline. Then the patients receive three intravenous pulses of methylprednisolone of 500 mg followed by oral prednisone 0.8-1.0 mg/kg/24h. The same measurements are repeated 4, 7 and 30 days after starting the steroid treatment.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Michał Nowicki, Prof. MD.; Phone Number: + 48 42 2014400; Email: nefro@wp.pl
• Study Contact Backup: Name: Katarzyna Pęczek, Dr; Email: katarzyna.peczek90@gmail.com

Study Locations

• Poland
  • Łódź, Poland
    • Recruiting
    • Medical University of Lodz, Poland
    • Contact: Ireneusz Staroń, Study Chair; Email: ireneusz.staron@umed.lodz.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patients with primary glomerular disease who are diagnosed and hospitalized in Nephrology Department in Łódź.

Description

Inclusion Criteria:

• previous diagnosed primary glomerular disease based on both clinical and renal biopsy findings
• an estimated glomerular filtration rate ≥15 ml/min/1.73m2
• proteinuria ≥2.0 g/24h

Exclusion Criteria:

• secondary glomerular disease
• acute kidney injury
• acute or chronic inflammation
• malignancy
• uncontrolled hypertension with systolic blood pressure higher than 160 mmHg
• symptomatic hypotension
• advanced heart failure
• history of non-compliance, dementia or depression

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study population; Plasma levels of SIRT-1, IL-6, FGF-23, sclerostin, calcium, phosphate, PTH and urine excretion of total protein, albumin, creatinine, calcium and phosphate are measured at baseline. Then the patients receive three intravenous daily pulses of methylprednisolone of 500 mg followed by oral prednisone 0.8-1.0 mg/kg/24h. The same measurements are repeated 4, 7 and 30 days after starting the steroid treatment.

Drug: Methylprednisolone, prednisone; The patients receive intravenous pulses of methylprednisolone 20-30 mg/kg/day for three consecutive days followed by oral prednisone 0.8-1.0 mg/kg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the change of plasma SIRT-1 level after glucocorticoids administration	30 days
the change of plasma sclerostin level after glucocorticoids administration	30 days
the change of plasma FGF-23 level after glucocorticoids administration	30 days
the change of plasma IL-6 level after glucocorticoids administration	30 days
the change of plasma total calcium level after glucocorticoids administration	30 days
the change of plasma phosphate level after glucocorticoids administration	30 days
the change of plasma PTH level after glucocorticoids administration	30 days
the change of urine albumin/creatinine ratio after glucocorticoids administration	30 days
the change of urine total protein/creatinine ratio after glucocorticoids administration	30 days
the change of urine phosphate/creatinine ratio after glucocorticoids administration	30 days
the change of urine calcium/creatinine ratio after glucocorticoids administration	30 days

Collaborators and Investigators

• Sponsor: Medical University of Lodz
• Investigators: Principal Investigator: Michał Nowicki, Prof. MD., Department of Nephrology, Hypertension and Kidney Transplantation Medical University of Lodz, Poland

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): July 30, 2021
• Study Completion (Anticipated): July 30, 2021

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: glucocorticoids; sclerostin; sirtuin-1; primary glomerular disease
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone
• Other Study ID Numbers: RNN/267/17/KE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No