Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
2 other identifiers
interventional
31
1 country
16
Brief Summary
In childhood nephrotic syndrome, the kidneys leak protein, causing body swelling and a variety of possible complications such as infection, blood clots, and kidney failure. The first-line treatment for nephrotic syndrome is corticosteroids. Many children respond to prednisone treatment, but the disease comes back (relapses) when the prednisone is stopped or the dose is reduced. Children with frequently relapsing or steroid dependent nephrotic syndrome are at risk for toxicity from frequent exposure to corticosteroids. Currently, the standard treatment for frequently relapsing and steroid dependent nephrotic syndrome involves a variety of medications that suppress the immune system, which can produce serious side effects. We propose a study to examine the effects of a different medication, ACTH, on nephrotic syndrome. ACTH is a hormone naturally found in the body. Recently, in adult studies, ACTH has been shown to be effective for the treatment of nephrotic syndrome. It has also been shown to have mild and reversible side effects. ACTH is potentially an attractive therapeutic alternative for the treatment of frequently relapsing and steroid dependent nephrotic syndrome in children. Our study will randomly assign patients with frequently relapsing or steroid dependent nephrotic syndrome to either ACTH treatment or no treatment. This will allow us to study the effects of ACTH on this disease and its side effects, by comparing how patients do on ACTH treatment versus no treatment. We hypothesize that ACTH gel is superior to no treatment in maintaining remission in children with frequently relapsing or steroid dependent nephrotic syndrome.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started May 2014
Typical duration for phase_3
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 12, 2013
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedFirst Posted
Study publicly available on registry
May 7, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2018
CompletedResults Posted
Study results publicly available
May 10, 2019
CompletedMay 29, 2019
May 1, 2019
3.7 years
December 12, 2013
March 4, 2019
May 16, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants Experienced a Relapse of Nephrotic Syndrome
Number of participants experienced a relapse of nephrotic syndrome during the initial 6 months of the study.
6 months
Secondary Outcomes (2)
Number of Participants Experiencing Relapses After Dose Reduction of ACTH
6 to 12 months
Number of Adverse Events
12 months
Study Arms (3)
Adrenocorticotropic hormone (ACTH)
ACTIVE COMPARATORPatients will receive ACTH twice weekly subcutaneously The initial dosing will be based on body surface area (BSA): 80 IU/1.73 m2 The patients will receive the initial dose for 6 months. At 6 months, the dose will be reduced by 50%. Patients who have side effects may have the dose reduced by 50% during the initial 6 months. A second dose reduction would still occur at 6 months (25% of initial dose).
No treatment
NO INTERVENTIONPatients in this treatment arm will receive no treatment to prevent relapses of nephrotic syndrome. A relapse, if it occurs, will be treated with prednisone and the patient will leave the no treatment arm of the study.
Rescue therapy
ACTIVE COMPARATORThere is an option for the patient in no-treatment arm to elect to be placed in the active treatment arm of the trial (rescue therapy).
Interventions
Patients will receive ACTH twice weekly for 6 months, with a 50% dose reduction allowed for side effects. The dose will be reduce by 50% at 6 months and continued for an additional 6 months.
Eligibility Criteria
You may qualify if:
- Age \>1 year at onset of nephrotic syndrome
- Age 2-20 years at time of randomization
- Estimated glomerular filtration rate (GFR) \> 50 ml/min/1.73 m2 at most recent measure prior to randomization (Schwartz formula)
- Steroid responsive nephrotic syndrome throughout clinical course (never required a second agent to attain remission of a relapse of nephrotic syndrome)
- History of frequently relapsing or steroid dependent nephrotic syndrome (defined as 2 or more relapses within 6 months after initial therapy or 4 or more relapses in any 12 month period OR relapse during taper or within 2 weeks of discontinuing prednisone).
- Patient is currently in relapse of nephrotic syndrome or had a relapse within the last 4 months (defined as an increase in the first morning urine protein to creatinine ratio ≥2 or Albustix reading of ≥2 for 3 or 5 consecutive days).
You may not qualify if:
- Prior treatment with ACTH.
- Cyclophosphamide or rituximab within the last 4 months.
- Lactation, pregnancy, or refusal of birth control in females with child-bearing potential
- Planned treatment with live or live-attenuated vaccines once enrolled in the study.
- Participation in another therapeutic trial concurrently or 30 days prior to randomization
- Active/serious infection (including, but not limited to Hepatitis B or C, HIV)
- Malignancy concurrently or within the last 2 years.
- Blood pressure \>95% for age/height while receiving maximal doses of 3 or more medications.
- Prior diagnosis of diabetes mellitus (Type I or II) or fasting glucose \>200mg/dL
- Organ transplantation
- Contraindications to Acthar: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction
- Secondary cause of nephrotic syndrome (e.g., SLE)
- Biopsy demonstrating a diagnosis other than minimal change, focal segmental glomerulosclerosis (FSGS) or a variant (mesangial proliferation, Immunoglobulin M nephropathy)
- Inability to consent/assent -
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Emory Universitylead
- Mallinckrodtcollaborator
Study Sites (16)
Pediatric Nephrology of Alabama, PC.
Birmingham, Alabama, 35205, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
Nemours/AI duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Emory University
Atlanta, Georgia, 30322, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Boston Children's Hopsital
Boston, Massachusetts, 02115, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Children's Mercy
Kansas City, Missouri, 64109, United States
Children's Hospital at Montefiore
The Bronx, New York, 10467, United States
Duke Children's Health Center
Durham, North Carolina, 27704, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23298, United States
Related Publications (1)
Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.
PMID: 39513526DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Greenbaum
- Organization
- Emory University
Study Officials
- PRINCIPAL INVESTIGATOR
Larry A Greenbaum, MD, PhD
Emory University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
December 12, 2013
First Posted
May 7, 2014
Study Start
May 1, 2014
Primary Completion
January 1, 2018
Study Completion
March 1, 2018
Last Updated
May 29, 2019
Results First Posted
May 10, 2019
Record last verified: 2019-05
Data Sharing
- IPD Sharing
- Will not share