Collapsing GlomerulopathyPhase 2NCT00098020
Podocyte Retinoids
A Phase 2 study testing Isotretinoin in people with Collapsing Glomerulopathy and Glomerulosclerosis, Focal Segmental, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This is a pilot study of retinoids for patients with unsatisfactory response to conventional treatment of nephrotic syndrome due to focal segmental glomerulosclerosis or minimal change disease, two renal disorders associated with putatively pathogenic malfunctioning of glomerular podocytes. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Collapsing Glomerulopathy, Glomerulosclerosis, Focal Segmental
- What is being tested?
- Isotretinoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 2004to 27 Jun 2016
- Phase
- Phase 2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with podocyte diseases, MCD, FSGS (including primary, secondary, and adaptive variants), and CG (including HIV-associated variant), who meet the following criteria:
- --An adequate renal biopsy, defined as having minimum 10 glomeruli for light microscopy and minimum 3 glomeruli for electron microscopy, unless the podocyte disease is diagnostic on fewer glomeruli. Patients who have non-diagnostic or technically inadequate biopsies will be offered the opportunity to undergo a research biopsy to determine eligibility. For some patients who have had a non-diagnostic or technically inadequate biopsy, a repeat renal biopsy may be clinically indicated in an effort to diagnose and treat a potentially serious kidney disease.
- Greater than or equal to 16 years of age. The rationale for excluding younger children is that retinoids may carry greater toxicity in children, as there are reports of premature epiphyseal closure, development of slender long bones, and periostal thickening.
- Prior treatment with at least two immunosuppressive agents that have been shown to induce remission in MCD and FSGS: glucocorticoids, cyclosporine, tacrolimus, cyclophosphamide, chlorambucil, and mycophenolate mofetil. Therapy with each agent must last at least 8 weeks. Exemptions will be made for those with contraindications to these medications or those who cannot tolerate these medications. The rationale is to recruit patients who have failed conventional therapy. All patients will be off immunosuppression for at least 4 weeks before starting retinoids in order to avoid a confounding effect.
- Three first void urine protein/creatinine ratios > 2 g/g obtained within one month prior to enrolling in the study. These urine collections will be obtained after the patient has been on a stable dose of angiotensin converting enzyme(ACE) inhibitor or angiotensin receptor blocker (ARB) for at least 4 weeks (the maximal antiproteinuric effect of these medications occurs after 4 weeks). The rationale is that patients with nephrotic-range proteinuria are at high risk for progressive renal disease, justifying participation in a clinical trial with novel agents. Patients with steroid-sensitive frequently relapsing MCD will not be required to have used ACE inhibitor or ARB, as steroids alone are typically sufficient therapy to induce remission.
- If hypertensive: blood pressure of less than or equal to 140/90 on a stable dose of ACE inhibitor or ARB for at least 1 month or greater than or equal to 75 percent of measurements before the entry of the study. The rationale is that uncontrolled hypertension can exacerbate proteinuria.
Who cannot join
- Pregnancy, breastfeeding, or unwillingness to use at least two contraceptive methods (at least one of which must be primary, including tubal ligation, partner vasectomy, oral contraceptives, implanted contraceptives, and intrauterine device). The rationale is that retinoids are teratogenic and are excreted in breast milk.
- Abnormal liver function test, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or protime. The rationale is that retinoids can be hepatotoxic. The only exception will be the following: if the cause of abnormality of liver function tests (LFT) is felt to be due to a specific hepatotoxic drug such as a statin and the levels are less than 2 times the upper limit of the normal AND normalize upon holding the offending drug, patients may be considered for study participation after consultation with hepatology service.
- Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride as this can lead to pancreatitis.
- Any medical conditions requiring concurrent immunosuppression, as this pilot study is designed to evaluate the effect of retinoids as a monotherapy.
- Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline, due to enhanced risk of increased intracranial pressure.
- Hypersensitivity to retinoids.
Show all 12Show fewer
- Presence of any unstable cardiovascular disease, uncontrolled diabetes with hemoglobin A1c greater than 8 percent, chronic inflammatory or infectious conditions except HIV-1 infection. Retinoids have been associated with chest pain of unclear etiology, increased serum glucose, myelosuppression and increased risk of infection. The etiology of infection is not clear but may be related to myelosuppression.
- Those with HIV-1 infection must not have any evidence for opportunistic infectious complications and have cluster of differentiation 4 (CD4) count greater than or equal to 200. Both tretinoin and isotretinoin have been safely studied in HIV-infected patients for other indications.
- glomerular filtration rate (GFR) less than 40 ml/min/1.73m(2) estimated by 5-variable Modification of Diet in Renal Disease (MDRD) equation, as the metabolites of retinoids are excreted in part in urine, and there is a concern for increased toxicity. In participants less than 18 years of age, we will use Schwartz equation.
- Expansion of glomerulus or interstitial formation on the biopsy.
- Untreated depression, as retinoids have been associated with depression, suicidal ideation, and aggressive behavior. If patients manifest significant depressive symptoms, they will be included in the study only if assessed and agreed by a psychiatrist (either at NIH or other) and if they have regular follow-up visits with a psychiatrist.
- Factors that increase the risk of renal biopsy. These include the following: unwillingness to accept blood transfusion, bleeding diathesis, single kidney, small kidneys (less than 9.5 cm).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Retinoids for Podocyte Disease
This is a pilot study of retinoids for patients with unsatisfactory response to conventional treatment of nephrotic syndrome due to focal segmental glomerulosclerosis or minimal change disease, two renal disorders associated with putatively pathogenic malfunctioning of glomerular podocytes. The hypothesis that retinoids may have reparative effects on these cells is based on previous research showing that retinoids promote the differentiation or redifferentiation of aberrant epithelial cells. Results obtained by 6 months of treatment with retinoids (that have been approved for non-renal indications) will be used as preliminary information upon which to base further testing of these agents in formal clinical trials in refractory cases of these nephrotic syndromes.
Read the detailed description
Retinoids are analogues of vitamin A that regulate cellular differentiation, leading to therapeutic use in skin diseases and malignancy. In animal models of kidney diseases, retinoids restore podocyte phenotype toward normal and reduce proteinuria. The objective of this phase II trial is to evaluate safety and develop preliminary evidence of efficacy of retinoid treatment in patients with podocyte disease. The study design is an open-label trial of isotretinoin (13-cis retinoic acid). The study will be performed under the auspices of an investigational new drug (IND) from the FDA. We will enroll 10 adult patients with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or collapsing glomerulopathy (CG). Inclusion criteria will include a prior trial of immunosuppressive therapy and proteinuria greater than or equal to 3.5 g/d while on angiotensin antagonist therapy.
The duration of the trial will be 6 months with possible additional 6-month extension for patients who only develop partial response (PR) or limited response (LR). Those who have complete response (CR) will continue the treatment for one additional month, for no more than 7 months total. Non-responders will stop at the end of 6 months. The primary clinical endpoint will be reduction in proteinuria as compared to the baseline value assessed by paired t test. The secondary clinical endpoints will be the fraction of patients who achieve CR or PR at 6 months and at one year, confirmed on urine collections four weeks apart. Retinoid therapy will be discontinued at the time a CR is confirmed, one month after the first detection of CR. Follow-up will last one year after cessation of drug therapy. Patients who have had a CR or PR but experience a relapse with >2.0g/g proteinuria during follow-up will be eligible for further retinoid therapy. Patients will undergo a renal biopsy prior to initiating therapy, in order to evaluate the extent of glomerular injury and interstitial fibrosis, unless they have had a kidney biopsy within the preceding 24 months that is available for review. Laboratory endpoints will include serum and urine cytokine levels and urine levels of podocyte proteins, including nephrin. Toxicity screening will include serum and urine chemistries, psychological profiles, radiographic films of cervical, thoracic spines and calcanei, and bone mass assessment with dual photon excitation absorptiometry (DEXA) at spine and hip.
- Being tested
- Isotretinoin
- Keywords
- Glomerulosclerosis, Proteinuria, Fibrosis, Chronic Kidney Disease, Nephrotic Syndrome
- Medical subject headings
- Glomerulosclerosis, Focal Segmental, Proteinuria, Fibrosis, Renal Insufficiency, Chronic, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsotretinoinDrug
| Study group | Role | What they receive |
|---|---|---|
| Isotretinoin | Experimental | Subjects will be treated with Isotretinoin. Receives: Drug: Isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Proteinuria at Week 24 From Baseline
Change of proteinuria at Week 24 compared to the baseline using protein/creatinine ratio (PCR)
Measured: Baseline and Week 24
Secondary outcomes (1)
Number of Patients Who Are in Complete Remission (CR) or Partial Remission (PR) at 6 Months or at the End of One Year.
Based on 24hour proteinuria, response outcomes are defined as CR (complete remission): <0.3 g/g PR (partial remission): 50% fall from baseline and <2.0 g/g
Measured: End of one year from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2004 (estimated)
- Study start26 Nov 2004
- Primary completion27 Jun 2016
- Study completion27 Jun 2016
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 (3)Papers the sponsor has linked to this study.
- Other trials for Collapsing GlomerulopathyStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase II, open-label pilot study
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jeffrey B Kopp, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098020
- Sponsor's protocol ID
- 050015
- Other IDs
- 05-DK-0015
- Status last verified
- 4 Oct 2017
- First submitted
- 1 Dec 2004
- Last updated
- 13 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The stored samples for this trial include plasma, urine, and renal biopsy samples. The plasma and urine are collected for cytokine measurement. Renal biopsy is done to evaluate histologic and ultrastructural changes. Samples/Data will be shared with collaborating investigators.
Publications
WILSON JG, ROTH CB, WARKANY J. An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat. 1953 Mar;92(2):189-217. doi: 10.1002/aja.1000920202. No abstract available.
PubMed 13030424Lelievre-Pegorier M, Vilar J, Ferrier ML, Moreau E, Freund N, Gilbert T, Merlet-Benichou C. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998 Nov;54(5):1455-62. doi: 10.1046/j.1523-1755.1998.00151.x.
PubMed 9844121Kriz W, Elger M, Nagata M, Kretzler M, Uiker S, Koeppen-Hageman I, Tenschert S, Lemley KV. The role of podocytes in the development of glomerular sclerosis. Kidney Int Suppl. 1994 Feb;45:S64-72. No abstract available.
PubMed 8158902
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retinoids for Podocyte Disease
- ClinicalTrials.gov ID
- NCT00098020
- Acronym / sponsor ID
- 050015
- Keywords
- Glomerulosclerosis, Proteinuria, Fibrosis, Chronic Kidney Disease, Nephrotic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 26 Nov 2004
- Primary completion
- 27 Jun 2016 (actual)
- Study completion
- 27 Jun 2016 (actual)
- First posted
- 2 Dec 2004 (estimated)
- Results
- Posted 13 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study of retinoids for patients with unsatisfactory response to conventional treatment of nephrotic syndrome due to focal segmental glomerulosclerosis or minimal change disease, two renal disorders associated with putatively pathogenic malfunctioning of glomerular podocytes. The hypothesis that retinoids may have reparative effects on these cells is based on previous research showing that retinoids promote the differentiation or redifferentiation of aberrant epithelial cells. Results obtained by 6 months of treatment with retinoids (that have been approved for non-renal indications) will be used as preliminary information upon which to base further testing of these agents in formal clinical trials in refractory cases of these nephrotic syndromes.
Detailed description
Retinoids are analogues of vitamin A that regulate cellular differentiation, leading to therapeutic use in skin diseases and malignancy. In animal models of kidney diseases, retinoids restore podocyte phenotype toward normal and reduce proteinuria. The objective of this phase II trial is to evaluate safety and develop preliminary evidence of efficacy of retinoid treatment in patients with podocyte disease. The study design is an open-label trial of isotretinoin (13-cis retinoic acid). The study will be performed under the auspices of an investigational new drug (IND) from the FDA. We will enroll 10 adult patients with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or collapsing glomerulopathy (CG). Inclusion criteria will include a prior trial of immunosuppressive therapy and proteinuria greater than or equal to 3.5 g/d while on angiotensin antagonist therapy.
The duration of the trial will be 6 months with possible additional 6-month extension for patients who only develop partial response (PR) or limited response (LR). Those who have complete response (CR) will continue the treatment for one additional month, for no more than 7 months total. Non-responders will stop at the end of 6 months. The primary clinical endpoint will be reduction in proteinuria as compared to the baseline value assessed by paired t test. The secondary clinical endpoints will be the fraction of patients who achieve CR or PR at 6 months and at one year, confirmed on urine collections four weeks apart. Retinoid therapy will be discontinued at the time a CR is confirmed, one month after the first detection of CR. Follow-up will last one year after cessation of drug therapy. Patients who have had a CR or PR but experience a relapse with >2.0g/g proteinuria during follow-up will be eligible for further retinoid therapy. Patients will undergo a renal biopsy prior to initiating therapy, in order to evaluate the extent of glomerular injury and interstitial fibrosis, unless they have had a kidney biopsy within the preceding 24 months that is available for review. Laboratory endpoints will include serum and urine cytokine levels and urine levels of podocyte proteins, including nephrin. Toxicity screening will include serum and urine chemistries, psychological profiles, radiographic films of cervical, thoracic spines and calcanei, and bone mass assessment with dual photon excitation absorptiometry (DEXA) at spine and hip.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase II, open-label pilot study
| Arm | Type | Receives |
|---|---|---|
| Isotretinoin | Experimental | Drug: IsotretinoinSubjects will be treated with Isotretinoin. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with podocyte diseases, MCD, FSGS (including primary, secondary, and adaptive variants), and CG (including HIV-associated variant), who meet the following criteria:
- --An adequate renal biopsy, defined as having minimum 10 glomeruli for light microscopy and minimum 3 glomeruli for electron microscopy, unless the podocyte disease is diagnostic on fewer glomeruli. Patients who have non-diagnostic or technically inadequate biopsies will be offered the opportunity to undergo a research biopsy to determine eligibility. For some patients who have had a non-diagnostic or technically inadequate biopsy, a repeat renal biopsy may be clinically indicated in an effort to diagnose and treat a potentially serious kidney disease.
- Greater than or equal to 16 years of age. The rationale for excluding younger children is that retinoids may carry greater toxicity in children, as there are reports of premature epiphyseal closure, development of slender long bones, and periostal thickening.
- Prior treatment with at least two immunosuppressive agents that have been shown to induce remission in MCD and FSGS: glucocorticoids, cyclosporine, tacrolimus, cyclophosphamide, chlorambucil, and mycophenolate mofetil. Therapy with each agent must last at least 8 weeks. Exemptions will be made for those with contraindications to these medications or those who cannot tolerate these medications. The rationale is to recruit patients who have failed conventional therapy. All patients will be off immunosuppression for at least 4 weeks before starting retinoids in order to avoid a confounding effect.
- Three first void urine protein/creatinine ratios > 2 g/g obtained within one month prior to enrolling in the study. These urine collections will be obtained after the patient has been on a stable dose of angiotensin converting enzyme(ACE) inhibitor or angiotensin receptor blocker (ARB) for at least 4 weeks (the maximal antiproteinuric effect of these medications occurs after 4 weeks). The rationale is that patients with nephrotic-range proteinuria are at high risk for progressive renal disease, justifying participation in a clinical trial with novel agents. Patients with steroid-sensitive frequently relapsing MCD will not be required to have used ACE inhibitor or ARB, as steroids alone are typically sufficient therapy to induce remission.
Key exclusion criteria (12 listed)
- Pregnancy, breastfeeding, or unwillingness to use at least two contraceptive methods (at least one of which must be primary, including tubal ligation, partner vasectomy, oral contraceptives, implanted contraceptives, and intrauterine device). The rationale is that retinoids are teratogenic and are excreted in breast milk.
- Abnormal liver function test, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or protime. The rationale is that retinoids can be hepatotoxic. The only exception will be the following: if the cause of abnormality of liver function tests (LFT) is felt to be due to a specific hepatotoxic drug such as a statin and the levels are less than 2 times the upper limit of the normal AND normalize upon holding the offending drug, patients may be considered for study participation after consultation with hepatology service.
- Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride as this can lead to pancreatitis.
- Any medical conditions requiring concurrent immunosuppression, as this pilot study is designed to evaluate the effect of retinoids as a monotherapy.
- Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline, due to enhanced risk of increased intracranial pressure.
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 |
|---|---|---|
| Isotretinoin | Drug | Isotretinoin |
Primary outcome
Change in Proteinuria at Week 24 From Baseline
Time frame: Baseline and Week 24
Change of proteinuria at Week 24 compared to the baseline using protein/creatinine ratio (PCR)
1 secondary outcome
Number of Patients Who Are in Complete Remission (CR) or Partial Remission (PR) at 6 Months or at the End of One Year.
Time frame: End of one year from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 13030424WILSON JG, ROTH CB, WARKANY J. An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat. 1953 Mar;92(2):189-217. doi: 10.1002/aja.1000920202. No abstract available.
- Background: PubMed 9844121Lelievre-Pegorier M, Vilar J, Ferrier ML, Moreau E, Freund N, Gilbert T, Merlet-Benichou C. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998 Nov;54(5):1455-62. doi: 10.1046/j.1523-1755.1998.00151.x.
- Background: PubMed 8158902Kriz W, Elger M, Nagata M, Kretzler M, Uiker S, Koeppen-Hageman I, Tenschert S, Lemley KV. The role of podocytes in the development of glomerular sclerosis. Kidney Int Suppl. 1994 Feb;45:S64-72. No abstract available.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The stored samples for this trial include plasma, urine, and renal biopsy samples. The plasma and urine are collected for cytokine measurement. Renal biopsy is done to evaluate histologic and ultrastructural changes. Samples/Data will be shared with collaborating investigators.
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.
Jeffrey B Kopp, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isotretinoin in people with Collapsing Glomerulopathy and Glomerulosclerosis, Focal Segmental, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 12 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 13 Dec 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 13 Dec 2017). 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?
Change in Proteinuria at Week 24 From Baseline (time frame: Baseline and Week 24). 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 NCT00098020, which also lists 3 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 13 Dec 2017.