Dose-Finding Pilot Study of ACTH in Patients With Idiopathic Membranous Nephropathy (MN)
Primary Purpose
Idiopathic Membranous Nephropathy
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ACTH
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Membranous Nephropathy
Eligibility Criteria
Inclusion Criteria:
- Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.
- Age > 18 years.
- Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure
- Proteinuria of >4.0 on a 24-hour urine collection.
- Estimated GFR >40 ml/min/1.73m2 while taking ACEI/ARB therapy.
Exclusion Criteria:
- Age <18 years.
- Estimated GFR <40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl.
- Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy.
- Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for >1 month, and alkylating agents or rituximab for >6 months.
- Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids.
- Patients with active infections or secondary causes of MN.
- Type 1 or 2 diabetes mellitus.
- Pregnancy or nursing.
- Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.
Sites / Locations
- Mayo Clinic
- University of Toronto
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm 1 ACTH 40 units
Arm 2 ACTH 80 units
Arm Description
Receive ACTH at the dose of 40 units sub-cutaneously for up to 12 weeks. If at day 91 no response has been shown, you will have the option to increase the dose of ACTH to 80 units for up to an additional 120 days.
Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks.
Outcomes
Primary Outcome Measures
Change in proteinuria
Change in LDL cholesterol, HDL cholesterol, and triglycerides
Change in side effects/toxicity
Secondary Outcome Measures
Number of subjects with CR or PR
The effect of maximizing angiotensin II blockade on proteinuria
Full Information
NCT ID
NCT00805753
First Posted
December 9, 2008
Last Updated
October 10, 2014
Sponsor
Mayo Clinic
Collaborators
Mallinckrodt
1. Study Identification
Unique Protocol Identification Number
NCT00805753
Brief Title
Dose-Finding Pilot Study of ACTH in Patients With Idiopathic Membranous Nephropathy
Acronym
MN
Official Title
A Dose-Finding Pilot Study of ACTH on the Serum Lipoprotein Profile and Proteinuria in Patients With Idiopathic Membranous Nephropathy (MN)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Mallinckrodt
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This pilot study is aimed at demonstrating the effectiveness of ACTH (H.P. Acthar Gel) on the lipid profile and proteinuria in participants with MN. ACTH or adrenocorticotrophin is a hormone produced by the pituitary gland (a gland at the base of your brain) that is involved in stimulating your adrenal glands to secrete a number of steroid products (e.g. cortisol, aldosterone, corticosterone, and others) that are important in keeping you alive. The drug used in this study has been approved by the Food and Drug Administration (FDA) for routine clinical use in the treatment of patients with proteinuria and patients with idiopathic nephrotic syndrome such as idiopathic MN. However, the most adequate dose to use has not been adequately assessed. This is the reason for conducting this research study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Membranous Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 ACTH 40 units
Arm Type
Active Comparator
Arm Description
Receive ACTH at the dose of 40 units sub-cutaneously for up to 12 weeks. If at day 91 no response has been shown, you will have the option to increase the dose of ACTH to 80 units for up to an additional 120 days.
Arm Title
Arm 2 ACTH 80 units
Arm Type
Active Comparator
Arm Description
Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
ACTH
Other Intervention Name(s)
H.P. Acthar Gel
Intervention Description
comparison of different dosages of drug
Primary Outcome Measure Information:
Title
Change in proteinuria
Time Frame
baseline, 3 months
Title
Change in LDL cholesterol, HDL cholesterol, and triglycerides
Time Frame
baseline, 3 months
Title
Change in side effects/toxicity
Time Frame
baseline, 3 months
Secondary Outcome Measure Information:
Title
Number of subjects with CR or PR
Time Frame
3 months
Title
The effect of maximizing angiotensin II blockade on proteinuria
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.
Age > 18 years.
Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure
Proteinuria of >4.0 on a 24-hour urine collection.
Estimated GFR >40 ml/min/1.73m2 while taking ACEI/ARB therapy.
Exclusion Criteria:
Age <18 years.
Estimated GFR <40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl.
Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy.
Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for >1 month, and alkylating agents or rituximab for >6 months.
Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids.
Patients with active infections or secondary causes of MN.
Type 1 or 2 diabetes mellitus.
Pregnancy or nursing.
Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando C Fervenza, M.D., Ph.D
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5R 0A3
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
34778952
Citation
von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
Results Reference
derived
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Dose-Finding Pilot Study of ACTH in Patients With Idiopathic Membranous Nephropathy
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