Safety and Efficacy of Acthar Gel in an Outpatient Dialysis Population

Study Overview
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Brief Summary
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This will be a prospective observational study of Acthar Gel in Non-Diabetic Hemodialysis [NDHD] patients receiving dialysis for ≤ 2 years. The project will aimed at providing proof-of-concept data that 80 U two times [2x] week Acthar for 6 months is a safe and effective therapy for NDHD. Effectiveness of lower dose 40 U 2X week will also be determined. Therefore the study will be a repeated measures design (Time x condition) comparison of improvement in renal function, nutritional status, quality of life and physical performance resulting from Acthar therapy.

Detailed Description
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Recent reports demonstrated Acthar gel is effective to induce remission of proteinuria in the Nephrotic Syndrome patients (Bomback 2011, 2012). There are limited published reports documenting the clinical response (creatinine, proteinuria, serum albumin and cholesterol) to ACTHAR therapy in a non-diabetic hemodialysis population. In addition to renal dysfunction and high risk for mortality, individuals who receive dialysis also have decreased strength, low exercise capacity, poor physical functioning, and a low quality of life (Edgell 1996, Johansen, 2001). Strength deficits are well documented in those with End Stage Renal Disease [ESRD] (Cheema 2010, Yoda 2012). There are several reports documenting an association between strength and gait deficits and other measures of physical performance in persons with ESRD (Bohannon 1994, Fitts 1997, Segura-Orti 2011). It is well known that measures of physical performance may predict risk for fall and hospitalization in older individuals (Guralnik JM, 2000). Deficits to physical performance may be further compounded by poor nutritional status. Persons with chronic renal disease, particularly in the context of hemodialysis or chronic renal replacement therapy, are often malnourished and/or are affected by abnormal micronutrient status (McMahon 2012). Furthermore, previous studies have shown that more than a third of acute-care, nephrology-related admissions are characterized by malnutrition (Lim 2012), and that it affects from 23% - 76% of all patients receiving hemodialysis (including outpatients)(Blumenkrantz 1980, Ikizler 1996, Pecoits-Filho 2002). Decreased functional status and concomitant malnutrition contribute to increased hospital readmissions, prolonged length of stay (and inevitably, increased medical costs), and increased morbidity and mortality patients (Isabel 2003, Lim 2012). Given the high prevalence of these characteristics in persons with renal disease, it is important to prioritize identification of novel and effective means by which to sustain and improve the functional capability of these patients, and to maintain their nutritional status and attenuate malnutrition. To date, there are no reports of the impact of Acthar gel therapy on renal function, strength, physical performance, nutritional status and quality of life in NDHD patients. This study will determine if Acthar gel therapy will maintain or improve overall kidney function as measured with 24 hour urine study at baseline and at the end of study period. In addition this study will determine if Acthar gel therapy will improve nutritional, physical and biochemical status in an outpatient non-diabetic hemodialysis population.

Official Title
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Safety and Efficacy of Acthar Gel in an Outpatient Dialysis Population

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Acthar Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria will be individuals requiring dialysis for treatment of ESRD who have had poor response to immunosuppressive strategies. Non-Diabetic Adults age 18-80 Exclusion Criteria: receiving hemodialysis for > 5 years diabetic, less than 18 years of age are pregnant have a history of cancer in the last 5 years have an active infection have recently had a myocardial infarction (within 6 weeks) have malignant arrhythmias, unstable angina, uncontrolled hypertension (SBP> 180 and/or DBP > 105) recent hospitalization (< 30 days), ocular disease, accelerated osteoporosis, gastrointestinal diseases (ulcerative colitis, diverticulitis, myasthenia gravis) any disorder that may be exacerbated by short periods of activity. cognitive dysfunction neurological deficits leading to limited ambulation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 80 Units of Acthar<br>Subjects assigned by random assignment to receive 80 Units of Acthar Gel 2x weekly for 6 months | Drug: Acthar Gel<br>* Subjects will be given an injection subcutaneously 2x week for 6 months. Dosing will be randomly assigned as either 80 U or 40 U<br>* Other names: repository corticotropin injection;|
| Active Comparator: 40 Units of Acthar<br>Subjects assigned by random assignment to receive 40 Units of Acthar Gel 2x weekly for 6 months | Drug: Acthar Gel<br>* Subjects will be given an injection subcutaneously 2x week for 6 months. Dosing will be randomly assigned as either 80 U or 40 U<br>* Other names: repository corticotropin injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function | Maintain or improve renal function [Creatinine clearance and Proteinuria] by ≥ 20% , as measured by eGFR or 24 hour urine study. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperparathyroidism | Change in serum parathyroid hormone levels | 6 months | 
| Anemia | Change in hemoglobin levels | 6 months | 
| Inflammatory blood markers | Change in serum C-Reactive Protein and Creatine Kinase | 6 months | 
| Vitamin D uptake | Change in Vitamin D dosing requirements | 6 months | 
| Hypercalcemia | Change in serum calcium levels | 6 months | 
| Phosphate | Change in serum phosphate levels | 6 months | 
| Total Iron Binding Capacity | Change in Total Iron Binding Capacity in serum | 6 months | 
| Epogen Dose | Change in epogen dosing requirements | 6 months | 
| Fall risk | Timed Up and Go Test will improve | 6 months | 
| Walking endurance | 2 minute walk distance | 6 months | 
| Gait speed | 10 meter gait speed test | 6 months | 
| Mobility disablement risk | Short Performance Physical Battery | 6 months | 
| Habitual Physical Activity | Physical Activity Scale for the Elderly | 6 months | 
| Calf Strength | Heel Rise Test | 6 months | 
| Quality of life | Medical Outcome Study Short Form 36 | 6 months | 
| Fear of Falling | ABC Scale [Activities-specific Balance Confidence Scale-Powell]. Scores to be above 67. | 6 months | 
| Self- Report Physical Activity | RAPA [Rapid Assessment of Physical Activity-Univ of Washington] | 6 months | 
| Nutritional Status | Body Mass Index | 6 months | 
| Lean body mass | Body Composition examination using Noori (2012) regression equation for lean body mass. | 6 months | 
| Caloric intake | Food Frequency Questionnaire (indicator of habitual intake) | 6 months | 
| Strength | Muscle force measures in 8 muscle groups | 6 months | 
| Nutritional Indices | Pre-Albumin | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acthar, Kidney, Dialysis, Non-Diabetic