Clinical trial NCT03025828: Adrenocorticotropic Hormone in Membranous Nephropathy
Official title: Changes in Autoreactive Memory B Cells as Biomarker of Response to Adrenocorticotropic Hormone in Patients With Membranous Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Membranous Nephropathy
Keywords: Membranous nephropathy
adrenocorticotropic hormone
ACTH
proteinuria
glomerulonephritis
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2017-01-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Proteinuria
timeFrame: baseline and 12 months
Secondary outcomes:
measure: Number of Participants With Complete or Partial Remission
timeFrame: 12 months
measure: Change in Serum Albumin
timeFrame: baseline 6 months, 12 months
measure: Estimated Glomerular Filtration Rate (GFR)
timeFrame: baseline and 12 months
measure: Number of Anti-PLA2R Memory B Cells
timeFrame: 12 months
measure: Anti-PLA2R Antibodies Levels
timeFrame: 12 months
measure: Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio
timeFrame: baseline and 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Paolo Cravedi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: