Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
Primary Purpose
Kidney Diseases
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
H.P. Acthar Gel
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Diseases
Eligibility Criteria
Inclusion Criteria:
- 1. Biopsy proven FSGS
- 2. Ability to consent and complete study evaluations
- 3. Greater than 2g/day of proteinuria
- 4. No contraindications to treatment with corticosteroids or ACTH
- 5. Women of childbearing potential will agree to use effective forms of birth control throughout this study
Exclusion Criteria:
- 1. Known secondary cause of FSGS
- 2. Receiving active immune therapy (within 90 days)
- 3. Pregnancy
- 4. Creatinine >2.5 mg/dl
- 5. Uncontrolled HTN (>180/100mm Hg)
- 6. Diabetes
- 7. Acute or chronic infection
- 8. Severe comorbidity (active coronary, cerebrovascular disease, cancer, psychiatric disease)
- 9. Age < 16, >65 years
- 10. Evidence of untreated tuberculosis (+PPD or Ellispot Gold testing)
- 11. A known contraindication to ACTH. Corticotropin is considered contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine origin.
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
No arms
Arm Description
There are no arms to this study. All patients receive drug (H.P. Acthar Gel)
Outcomes
Primary Outcome Measures
24 Hour Proteinuria
Serum Creatinine
Protein/Creatinine Ratio
Secondary Outcome Measures
eGFR
Weight
Systolic Blood Pressure
Diastolic Blood Pressure
Glucose
Total Cholesterol
Full Information
NCT ID
NCT01155141
First Posted
June 29, 2010
Last Updated
August 20, 2014
Sponsor
Stanford University
Collaborators
Mallinckrodt
1. Study Identification
Unique Protocol Identification Number
NCT01155141
Brief Title
Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
Official Title
Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Mallinckrodt
4. Oversight
5. Study Description
Brief Summary
FSGS is an immunologic disorder wherein circulating immune proteins cause damage to the kidneys and progressive injury and scarring. Corticosteroid therapy is occasionally, but not nearly universally, successful in reducing proteinuria, and when patients respond, they have a favorable prognosis. The investigators believe that ACTH therapy (H.P. Acthar Gel) can provide a more rapid, well tolerated reduction in glomerular injury.
Detailed Description
EXPERIMENTAL TREATMENT: Patients with biopsy proven FSGS will be treated with ACTH in an open-label pilot study of tolerability and efficacy. The investigators will recruit 18-20 patients to complete this study, over 2 years.
ACTH therapy: Patients will receive H.P. Acthar gel IM or SQ, initially at 40 IU SQ every week for 16 weeks of therapy. All patients will be treated to goal BP of <140/90mmHg with all patients treated with ACEi or ARB therapy as tolerated. H2 receptor blockade or proton pump inhibitor therapy will also be offered all patients. Dose will be titrated up to 160 IU SQ every week, if at 1 month the patient has had no substantial reduction in proteinuria, no deterioration of blood pressure and no development of hyperglycemia as well as no serious adverse events felt to be related to the medication.
CLINICAL OUTCOME: Patients will be followed for the primary outcome of remission of proteinuria. This will be defined as partial remission when the proteinuria is reduced below 50% of the initial, pre treatment value and as complete remission when the proteinuria is reduced to < 0.5 g/g or <500 mg/day on a 24 hour urine sample. Secondary outcomes will include effects on eGFR, effects on glucose levels, effects on blood pressure (total doses of antihypertensive medications and absolute changes in blood pressure) and on immune status. Outcomes will be determined by looking at 3 month and 6 month values of urine protein and eGFR following initiation of treatment.
IMMUNOLOGIC TESTING: In order to further assess the role of immunologic perturations on FSGS and the effect of ACTH on the immune system, all patients will bank blood and urine before the start of the study for cytokine analysis, RNA, DNA, protein and protoarray testing.
MONITORING AND SAFETY: All patients will undergo full informed consent per the Stanford Institutional Review Board. Contact numbers will be provided and study staff will be available at all times in case of any medical emergencies. All patients will continue with routine health monitoring with a minimal of monthly assessments. A comprehensive interview will be undertaken to assess for side effects, complete physical exams will be accomplished including vital signs, CBC, clinical chemistries (including electrolytes, creatinine, glucose and liver function tests), urine for protein and creatinine and fasting lipid profiles every 3 months. Also at screening and baseline.
PATIENT WITHDRAWAL/TERMINATION OF STUDY: Patients will be closely monitored, as detailed above. Patients may voluntarily leave the study at any time, although every effort will be made to follow their clinical course and monitor for safety issues and possible benefits of therapy. Patient will be monitored for adverse events. Patients with severe adverse events will be evaluated for the relatedness of their event to the study medication. If the event is considered severe and possibly or probably related to the study medication, the medication will be discontinued and the patient will continue to be monitored. In the case the adverse event is possibly related, the medication may be restarted, if the investigator and subject agree. For patients with probably related severe adverse events, study treatment will be discontinued however, the investigators will still follow the patient to see if the course of their underlying disease was modified by treatment. As this is an open label, pilot study, no data safety monitoring board is felt to be necessary. If drug related SAEs develop in more than 20% of patients, the study will be submitted back to the IRB to determine if it should continue.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
No arms
Arm Type
Experimental
Arm Description
There are no arms to this study. All patients receive drug (H.P. Acthar Gel)
Intervention Type
Drug
Intervention Name(s)
H.P. Acthar Gel
Intervention Description
Patients were treated with 40 units subcutaneously (SC) weekly for 2 weeks, then dose increased to 80 units SC weekly for 2 weeks followed by 80 units SC twice weekly to complete 16 weeks of therapy.
Primary Outcome Measure Information:
Title
24 Hour Proteinuria
Time Frame
Baseline - Month 6
Title
Serum Creatinine
Time Frame
Baseline - Month 6
Title
Protein/Creatinine Ratio
Time Frame
Baseline - Month 6
Secondary Outcome Measure Information:
Title
eGFR
Time Frame
Baseline - Month 6
Title
Weight
Time Frame
Baseline - Month 6
Title
Systolic Blood Pressure
Time Frame
Baseline - Month 6
Title
Diastolic Blood Pressure
Time Frame
Baseline - Month 6
Title
Glucose
Time Frame
Baseline - Month 6
Title
Total Cholesterol
Time Frame
Baseline - Month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Biopsy proven FSGS
2. Ability to consent and complete study evaluations
3. Greater than 2g/day of proteinuria
4. No contraindications to treatment with corticosteroids or ACTH
5. Women of childbearing potential will agree to use effective forms of birth control throughout this study
Exclusion Criteria:
1. Known secondary cause of FSGS
2. Receiving active immune therapy (within 90 days)
3. Pregnancy
4. Creatinine >2.5 mg/dl
5. Uncontrolled HTN (>180/100mm Hg)
6. Diabetes
7. Acute or chronic infection
8. Severe comorbidity (active coronary, cerebrovascular disease, cancer, psychiatric disease)
9. Age < 16, >65 years
10. Evidence of untreated tuberculosis (+PPD or Ellispot Gold testing)
11. A known contraindication to ACTH. Corticotropin is considered contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine origin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Lafayette
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24009220
Citation
Hogan J, Bomback AS, Mehta K, Canetta PA, Rao MK, Appel GB, Radhakrishnan J, Lafayette RA. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013 Dec;8(12):2072-81. doi: 10.2215/CJN.02840313. Epub 2013 Sep 5.
Results Reference
derived
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Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
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