Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN) (ACTH-NRDN)

May 30, 2013 updated by: James A. Tumlin MD, Southeast Renal Research Institute

"Safety and Efficacy of Acthar Gel on Albuminuria and Urinary Transforming Growth Factor Excretion in Type I or Type II Diabetics Requiring Medical Treatment of Hyperglycemia With Nephrotic Range Proteinuria: A Pilot Study"

This is a prospective open labeled trial examining the efficacy of ACTHar Gel (porcine ACTH) on the level of proteinuria in patients with diabetic nephropathy and nephrotic range proteinuria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Diabetes Mellitus is a significant and growing health problem in the United States and other developed countries. Despite improving public awareness, end-organ complications including diabetic nephropathy and coronary atherosclerotic heart disease continues to grow by 5-10% per year. While improvements in the control of blood pressure and the wide-spread use of antagonists of the renin-angiotensin-aldosterone system have significantly improved renal outcomes, therapies designed to disrupt the more central pathogenic mechanisms of diabetic nephropathy are still needed. Recent observations have shown that effacement of podocyte foot-plate processes and accelerated apoptosis, are central to the pathogenesis of diabetic nephropathy. The resulting increase in glomerular permeability leads to nephrotic range proteinuria and interstitial fibrosis from local synthesis of transforming growth factor b (TGF-b) and direct toxicity to the renal epithelium. Recent studies have shown that synthetic forms of adrenocorticotropic hormone (ACTH) are able to achieve sustained reductions in proteinuria in non-diabetic glomerulopathies. Moreover, while the numbers of patients are quite limited, preliminary studies also suggest that pharmacologic administration of ACTH can reduce proteinuria in patients with diabetic nephropathy. The observation that ACTH can reduce proteinuria in a variety of glomerulopathies suggests that ACTH may be important for podocyte function and viability independent of the primary disease. Interestingly, recent studies confirm that melanocortin receptors are expressed in non-adrenal tissues including the circulating T and B cells and most recently the glomerular podocyte. Previous studies investigating the effect of diabetes and insulin therapy on ACTH levels have given mixed results. It is therefore unclear how podocytes in patients with diabetic nephropathy could become functionally deficient in ACTH. However, studies in adrenal cortical cells finds that TGF-b is able to down regulate the expression of ACTH receptors. Moreover, TGF-b is able block an ACTH-induced stimulation of melanocortin receptors. This intriguing link between TGF-b and ACTH signaling raises the question of whether impaired signaling of ACTH in the glomerulus leads to podocyte dysfunction, accelerated detachment and ultimately podocyte apoptosis. Moreover, we postulate that a complex interaction between TGF-b and ACTH expression exists within the glomerulus such that restoration of ACTH function will lead to a reduction in renal TGF-b expression. We therefore propose to study the effect of increasing doses of exogenous ACTH on rates of albuminuria and urinary TGF-b expression in diabetics with nephrotic range proteinuria. In addition to TGF-b we will examine whether a similar effect occurs on the 3 major isoforms of vascular endothelial growth factor, VEGF120, 164, and 180. We will also determine the duration of the effect and whether it is additive with ACE/ARB therapy inhibition.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Southeast Renal Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age > 18 and < 80
  2. Type I or Type II Diabetes Mellitus
  3. Stable ACE or ARB therapy for 4 weeks prior to study enrollment
  4. Urinary protein > 3000 mg/24 hrs
  5. Patients with more than one protein lowering agent (e.g. ACE or ARB, or MR antagonist or Tekturna require two consecutive 24 hour urinary protein of 2000 mg/24 hrs.

Exclusion Criteria:

  1. Age <18 or >80
  2. HgbA1c > 9.0% or 11% if using the (DCCT / NGSP) method.
  3. eGFR < 20 mls/min by MDRD formula or eGFR by (Cockoff-Gault 20 mls/min)
  4. Dilated cardiomyopathy with known EF < 40%
  5. Pregnant or nursing mothers
  6. Patients with an admission for diabetic ketoacidosis, or non-ketotic hyperosmolar coma within 6 months of study enrollment.
  7. Patients with known mixed glomerulonephritis and diabetic glomerulopathy
  8. Patients within 3 mths of operative procedures or chronic non-healing wounds
  9. Patients with glucocorticoid-induced diabetes mellitus
  10. Patients with known sensitivity to porcine protein products
  11. Patients with bleeding gastric or duodenal ulcers requiring hospitalization six months prior to study enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ACTH-16 units
Patients with nephrotic range proteinuria randomized to this group will receive 16 units ACTHargel sub-cutaneously every day.
Drug: ACTH
Patients with nephrotic range proteinuria randomized to this group will receive 16 units ACTHargel sub-cutaneously every day.
Other Names:
  • ACTHar Gel
Drug: ACTH
Patients with nephrotic range proteinuria randomized to this group will receive 32 units ACTHargel sub-cutaneously every day.
Other Names:
  • ACTHar Gel
Active Comparator: ACTH-32 units
Patients with nephrotic range proteinuria randomized to this group will receive 32 units ACTHargel sub-cutaneously every day.
Drug: ACTH
Patients with nephrotic range proteinuria randomized to this group will receive 16 units ACTHargel sub-cutaneously every day.
Other Names:
  • ACTHar Gel
Drug: ACTH
Patients with nephrotic range proteinuria randomized to this group will receive 32 units ACTHargel sub-cutaneously every day.
Other Names:
  • ACTHar Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients achieving less than 300 mg protein per 24 hours after 6 months of Acthar Gel.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients achieving greater than 50% reduction in urinary proteinuria after 6 months of Acthar Gel.
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southeast Renal Research Institute

Collaborators

Mallinckrodt

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

December 8, 2009

First Submitted That Met QC Criteria

December 8, 2009

First Posted (Estimate)

December 9, 2009

Study Record Updates

Last Update Posted (Estimate)

May 31, 2013

Last Update Submitted That Met QC Criteria

May 30, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTH-NRDN

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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