Dose-Finding Pilot Study of ACTH in Patients With Idiopathic Membranous Nephropathy (MN)

• ClinicalTrials.gov Identifier: NCT00805753
• Recruitment Status: Completed
• First Posted: December 10, 2008
• Last Update Posted: October 13, 2014
• Sponsor: Mayo Clinic
• Collaborator: Mallinckrodt
• Information provided by (Responsible Party): Fernando Fervenza, Mayo Clinic

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.

Condition or disease	Intervention/treatment	Phase
Idiopathic Membranous Nephropathy	Drug: ACTH	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dose-Finding Pilot Study of ACTH on the Serum Lipoprotein Profile and Proteinuria in Patients With Idiopathic Membranous Nephropathy (MN)
• Study Start Date: January 2009
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1 ACTH 40 units; 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.	Drug: ACTH; comparison of different dosages of drug; Other Name: H.P. Acthar Gel
Active Comparator: Arm 2 ACTH 80 units; Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks.	Drug: ACTH; comparison of different dosages of drug; Other Name: H.P. Acthar Gel

Outcome Measures

Primary Outcome Measures :

1. Change in proteinuria [ Time Frame: baseline, 3 months ]
2. Change in LDL cholesterol, HDL cholesterol, and triglycerides [ Time Frame: baseline, 3 months ]
3. Change in side effects/toxicity [ Time Frame: baseline, 3 months ]

Secondary Outcome Measures :

1. Number of subjects with CR or PR [ Time Frame: 3 months ]
2. The effect of maximizing angiotensin II blockade on proteinuria [ Time Frame: 3 months ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.
2. Age > 18 years.
3. 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
4. Proteinuria of >4.0 on a 24-hour urine collection.
5. Estimated GFR >40 ml/min/1.73m2 while taking ACEI/ARB therapy.

Exclusion Criteria:

1. Age <18 years.
2. Estimated GFR <40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl.
3. Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy.
4. Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for >1 month, and alkylating agents or rituximab for >6 months.
5. Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids.
6. Patients with active infections or secondary causes of MN.
7. Type 1 or 2 diabetes mellitus.
8. Pregnancy or nursing.
9. Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Canada, Ontario

University of Toronto

Toronto, Ontario, Canada, M5R 0A3

Sponsors and Collaborators

Mayo Clinic

Mallinckrodt

Investigators

• Principal Investigator: Fernando C Fervenza, M.D., Ph.D; Mayo Clinic

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fernando Fervenza, M.D., Ph.D., Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00805753
• Other Study ID Numbers: 08-006328
• First Posted: December 10, 2008
• Last Update Posted: October 13, 2014
• Last Verified: October 2014

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, Membranous; Urologic Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases