Treatment Resistant Nephrotic SyndromePhase 4NCT01129284
Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)
A Phase 4 study testing ACTHAR gel in people with Treatment Resistant Nephrotic Syndrome, run by Columbia University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment Resistant Nephrotic Syndrome
- What is being tested?
- ACTHAR gel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Sep 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult nephrotic patients, at least 18 years of age
- Diagnosis of focal segmental glomerulosclerosis (FSGS), resistant or relapsing minimal change disease with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: corticosteroids and at least one other immunosuppressive regimen
- Diagnosis of membranous nephropathy with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: either the "Ponticelli protocol" of alternating months of pulse steroids followed by oral steroids and then an alkylating agent with each regimen repeated for six full months of therapy or a calcineurin inhibitor, cyclosporine or tacrolimus, and at least one other therapy
- Diagnosis of immunoglobulin A nephropathy (IgAN) with persistent nephrotic range proteinuria in patients on ACE inhibition or angiotension receptor blockers (ARB) therapy to reduce proteinuria
- Willing and able to sign informed consent
- Patients of childbearing age must agree to use birth control
Who cannot join
- Patients under 18 years of age
- Patients unable to sign informed consent
- Patients having received rituximab or another monoclonal antibody within 6 months of the trial
- Patients of childbearing age who refuse to use birth control
- Patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73m2
- Patients with other renal diseases (e.g. diabetic nephropathy, renal vascular disease) that would interfere with interpretation of the study.
- Patients with comorbid conditions that would interfere with completion of the trial (malignancies, congestive heart failure (CHF), recent myocardial infarction).
- Patients with known contraindications to the use of H.P. ACTHAR Gel, including: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, and allergies to pork or pork products.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: The Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Treatment Resistant Nephrotic Syndrome
- Being tested
- ACTHAR gel
- Keywords
- Treatment Resistance, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, lipoid nephrosis, Membranous nephropathy, IgA nephropathy, proteinuria
- Medical subject headings
- Nephrotic Syndrome, Glomerulosclerosis, Focal Segmental, Nephrosis, Lipoid, Glomerulonephritis, Membranous, Glomerulonephritis, IGA, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACTHAR gelDrug
Also called H.P. Acthar gel
Patients will be treated with ACTHAR gel starting with 40 units given twice weekly subcutaneously for two weeks, then 80 units given twice weekly subcutaneously afterwards for a period of up to six months.
| Study group | Role | What they receive |
|---|---|---|
| Acthar gel | Experimental | Patients will be treated with ACTHAR gel starting with 40 units given twice weekly subcutaneously for two weeks, then 80 units given twice weekly subcutaneously afterwards for a period of up to six months. Receives: Drug: ACTHAR gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Significant Reduction in Proteinuria to Remission Levels During the Treatment Period (Includes Complete and Partial Remission, as Defined in the Outcome Measure Description Below)
Complete remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with proteinuria falling <500 mg/day at month 6. Partial remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with 50% reduction in proteinuria and final proteinuria 500-3500 mg/day at month 6.
Measured: 6 months
Secondary outcomes (1)
Sustained Remissions up to 1 Year After Discontinuing Therapy
Complete remission defined as stable or improved renal function, serum creatinine < or = 125% baseline, with proteinuria falling <500 mg/day at last follow-up visit (6 to 12 months post treatment). Partial remission defined as stable or improved renal function, serum creatinine < or = 125% baseline, with 50% reduction in proteinuria and final proteinuria 500-3500 mg/day at last follow-up visit (6 to 12 months post treatment).
Measured: Up to 1 year after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2010 (estimated)
- Study startDec 2009
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Principal investigator, Gerald B. Appel, Columbia University
- Investigators
- Gerald B Appel, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01129284
- Sponsor's protocol ID
- AAAD9539
- Status last verified
- Mar 2014
- First submitted
- 21 May 2010
- Last updated
- 24 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67. doi: 10.1159/000339287. Epub 2012 Jun 19.
PubMed 22722778Hogan 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.
PubMed 24009220
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)
- ClinicalTrials.gov ID
- NCT01129284
- Acronym / sponsor ID
- AAAD9539
- Conditions
- Treatment Resistant Nephrotic Syndrome
- Keywords
- Treatment Resistance, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, lipoid nephrosis, Membranous nephropathy, IgA nephropathy, proteinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Mallinckrodt
- Study start
- Dec 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 24 May 2010 (estimated)
- Results
- Posted 24 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acthar gel | Experimental | Drug: ACTHAR gelPatients will be treated with ACTHAR gel starting with 40 units given twice weekly subcutaneously for two weeks, then 80 units given twice weekly subcutaneously afterwards for a period of up to six months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult nephrotic patients, at least 18 years of age
- Diagnosis of focal segmental glomerulosclerosis (FSGS), resistant or relapsing minimal change disease with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: corticosteroids and at least one other immunosuppressive regimen
- Diagnosis of membranous nephropathy with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: either the "Ponticelli protocol" of alternating months of pulse steroids followed by oral steroids and then an alkylating agent with each regimen repeated for six full months of therapy or a calcineurin inhibitor, cyclosporine or tacrolimus, and at least one other therapy
- Diagnosis of immunoglobulin A nephropathy (IgAN) with persistent nephrotic range proteinuria in patients on ACE inhibition or angiotension receptor blockers (ARB) therapy to reduce proteinuria
- Willing and able to sign informed consent
Key exclusion criteria (8 listed)
- Patients under 18 years of age
- Patients unable to sign informed consent
- Patients having received rituximab or another monoclonal antibody within 6 months of the trial
- Patients of childbearing age who refuse to use birth control
- Patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACTHAR gelAlso: H.P. Acthar gelPatients will be treated with ACTHAR gel starting with 40 units given twice weekly subcutaneously for two weeks, then 80 units given twice weekly subcutaneously afterwards for a period of up to six months. | Drug | Acthar gel |
Primary outcome
Significant Reduction in Proteinuria to Remission Levels During the Treatment Period (Includes Complete and Partial Remission, as Defined in the Outcome Measure Description Below)
Time frame: 6 months
Complete remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with proteinuria falling <500 mg/day at month 6. Partial remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with 50% reduction in proteinuria and final proteinuria 500-3500 mg/day at month 6.
1 secondary outcome
Sustained Remissions up to 1 Year After Discontinuing Therapy
Time frame: Up to 1 year after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22722778Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67. doi: 10.1159/000339287. Epub 2012 Jun 19.
- Derived from this study: PubMed 24009220Hogan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald B Appel, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ACTHAR gel in people with Treatment Resistant Nephrotic Syndrome, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Significant Reduction in Proteinuria to Remission Levels During the Treatment Period (Includes Complete and Partial Remission, as Defined in the Outcome Measure Description Below) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01129284, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2014.