Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)

Overview

This study will examine the safety and effectiveness of ACTHAR Gel, when used to treat 15 patients diagnosed with "treatment resistant nephrotic syndrome." Nephrotic syndrome is a group of symptoms that includes low levels of protein in the blood, swelling of tissue (edema), especially around the eyes, feet and hands; and high plasma levels of cholesterol. It is caused by a variety of diseases and underlying disorders that damage the kidneys, resulting in excessive excretion of protein in the urine. These diseases damage the glomeruli, which are small blood vessels that filter wastes and excess water from the blood and pass them into the bladder as urine. As a result of protein loss in the urine, the blood is deficient in protein. Normal amounts of blood protein are needed to help regulate fluid throughout the body. Protein in the blood normally draws water from the tissues and into the bloodstream. When blood protein levels are low, the normal movement of water is reversed, and fluid is drawn from the blood and accumulates in the tissues. This excess tissue fluid causes the swelling and puffiness (edema) that is a symptom of nephrotic syndrome. Nephrotic syndrome is described as "treatment resistant" when a patient fails to achieve a sustained partial or complete remission after treatment with at least two first line therapies. The goal of this study is to determine whether injections of ACTHAR Gel (an FDA approved treatment for nephrotic syndrome) over a six month period will lead to a correction of treatment resistant nephrotic syndrome in these patients.

The nephrotic syndrome is characterized by heavy proteinuria, edema, hyperlipidemia, and a thrombotic tendency. Membranous nephropathy, focal segmental glomerulosclerosis, resistant minimal change disease, and Immunoglobulin A (IgA) nephropathy (also known as Berger's disease) are the common forms of idiopathic nephrotic syndrome in adults. Asymptomatic patients with idiopathic nephrotic syndrome may be treated with ACE inhibitors and /or angiotension receptor blockers to reduce proteinuria, with statins to treat hyperlipidemia, and diuretics to control edema. Patients with large amounts of proteinuria are refractory to such treatments and often require immunosuppressive medications to promote a remission of the proteinuria and the nephrotic syndrome and to prevent progressive renal failure. All such immunosuppressives have multiple potential serious side effects. Some patients either relapse after remissions of their proteinuria or are resistant to immunosuppressive therapy. A synthetic truncated analog of ACTH has been used in patients with the nephrotic syndrome in both uncontrolled trials and in a randomized controlled trial in membranous nephropathy. In uncontrolled studies it has led to sustained remissions of the nephrotic syndrome in multiple forms of idiopathic disease including membranous nephropathy and focal segmental glomerulosclerosis (FSGS). It has also led to reduction of total cholesterol, LDL cholesterol, Lpa, and elevations of HDL cholesterol. In a controlled randomized trial in membranous nephropathy it proved equivalent to an alternating monthly regimen of corticosteroids and an alkylating agent that is widely regarded as a first line therapy for this disease. This synthetic truncated analog of ACTH is not available in the US. ACTHAR gel is a natural, highly purified, porcine ACTH which is both available in the US and FDA approved for use in the nephrotic syndrome. Although ACTHAR gel has been used to treat large numbers of patients with multiple sclerosis and infantile paralysis annually, it has, however, been used in only small numbers of patients for the indication of the nephrotic syndrome.