Adrenocorticotropic Hormone in Membranous Nephropathy

Membranous Nephropathy Clinical Trial

Official title:

Changes in Autoreactive Memory B Cells as Biomarker of Response to Adrenocorticotropic Hormone in Patients With Membranous Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03025828
• Other study ID #: GCO 16-2402
• Status: Completed
• Phase: Phase 4
• Start date: March 19, 2018
• Est. completion date: December 16, 2020

Study information

• Verified date: July 2022
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of adrenocorticotropic hormone (ACTH, Acthar) on the loss of proteins in the urine (proteinuria) in patients with membranous nephropathy. Acthar is a hormone that stimulates steroid production from small glands above the kidneys. It has direct protective effects on the kidney and is currently approved by the FDA to treat kidney disorders associated with proteins in the urine, but the mechanisms of action are not entirely understood and will be studied in the present trial.

Description:

Patients with membranous nephropathy and nephrotic syndrome will be treated with ACTH for 6 months. Proteinuria remission at 12 months will be the primary endpoint. Different biomarkers including anti-PLA2R autoantibodies, circulating regulatory T cells, and autoreactive memory B cells will be serially measured to identify predictors of response to therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: December 16, 2020
• Est. primary completion date: December 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 18 to 70 years

• Free of immunosuppression for at least 3 months

• Capability of understanding the purpose of the study

• Written informed consent

Exclusion Criteria:

• Epidermal growth factor receptor (eGFR) < 30ml/min/1.73m2

• Kidney Transplant

• Secondary MN (defined on the basis of clinical criteria)

• Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion)

• History of previous use of Acthar for treatment of nephrotic syndrome

• Prior sensitivity to Acthar or other porcine protein products

• Contraindication to Acthar per Prescribing Information

• Planned treatment with live or live attenuated vaccines once enrolled in the study

• More than three previous treatment regiments

• Participation to other clinical trials over the previous 12 months

• History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas

• Pregnancy

• Lactation

• Current substance abuse

• Any clinically relevant condition that might affect study participation and/or study results

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Membranous Nephropathy

Intervention

Drug:
• ACTHar
for 6 months

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Proteinuria	Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio	baseline and 12 months
Secondary	Number of Participants With Complete or Partial Remission	Complete (proteinuria reduction <500mg/24h) or partial (urinary protein excretion (P/C) <3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission.	12 months
Secondary	Change in Serum Albumin	Change in serum albumin from baseline	baseline 6 months, 12 months
Secondary	Estimated Glomerular Filtration Rate (GFR)	GFR measures kidney function.	baseline and 12 months
Secondary	Number of Anti-PLA2R Memory B Cells	Number of anti-PLA2R memory B cells	12 months
Secondary	Anti-PLA2R Antibodies Levels	blood levels; Number of anti-PLA2R memory B cells	12 months
Secondary	Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio	blood levels - one single cell subset identified by different markers	baseline and 12 months