Epilepsy, Unspecified, IntractablePhase 4NCT02695797
Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody
A Phase 4 study testing IVIG and Prednisolone in people with Epilepsy, Unspecified, Intractable, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The purpose of the study is to investigate effect of immunotherapy in intractable cryptogenic epilepsy patients with autoimmune antibody. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Epilepsy, Unspecified, Intractable
- What is being tested?
- IVIG and Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSouth Korea
- Study dates
- Sep 2015to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of cryptogenic epilepsy according to the International League Against Epilepsy's Classification of Epilepsy.
- Intractable epilepsy: Complete seizure control is not achieved with trials of two appropriate antiepileptic drugs
- At least 1 seizure within the past 8 weeks
- Presence of autoimmune antibody (NMDAR, LGI1, CASPR2, AMPA1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/CRMP5, -amphiphysin, GAD) in serum or cerebrospinal fluid
- Written informed consent signed by the subject or legal guardian prior to entering the study
Who cannot join
- Clinical evidence of autoimmune encephalitis such as autoimmune limbic encephalitis
- History of severe head trauma
- Presence of structural abnormality which is thought to be epileptogenic in brain MRI
- Epilepsy of predominantly genetic or presumed genetic origin
- An active CNS infection, demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results History of immunotherapy
- A history of nonepileptic or psychogenic seizures within past 1 year
Show all 10Show fewer
- Any clinically significant laboratory abnormality that in the opinion of the Investigator would exclude the subject from the study
- Any clinically significant psychiatric illness, psychological, or behavioral problems that, in the opinion of the Investigator, would interfere with the subject's ability to participate in the study
- Recent (within 4 weeks) change or dose adjustment of anti-epileptic drug (1 to 2 doses of rescue benzodiazepine is permitted)
- Refuse to participate in the study
Trial locations and contacts
1 site in 1 country.
Kon Chu, Professor contact
Jung-Ah Lim, Fellow contact
South Korea1 site, 1 recruiting
- Recruiting
Seoul National University Hospital
Seoul
Kon Chu, Professor, stemcell.snu@gmail.com
Jung-Ah Lim, Fellow, jungah0118@gmail.com
About this study
The purpose of the study is to investigate effect of immunotherapy in intractable cryptogenic epilepsy patients with autoimmune antibody.
Read the detailed description
Cryptogenic epilepsy is an epilepsy of presumed symptomatic nature but the cause has not been identified. It account for at least 40% of adult-onset epilepsy. Autoimmune encephalitis including classic paraneoplastic syndrome and autoimmune synaptic encephalitis is a new category of immune-mediated disorders which often has favorable outcome. Recent studies reported that immunotherapy improves seizure outcome in medically intractable epilepsy patients with clinical and serological evidence of an autoimmune basis. Neural autoantibodies were detected in 22% of epilepsy due to unknown cause in a study, mostly from the antiepileptic drug(AED)-resistant epilepsy group. Of the patients who received immunotherapy, 75% archived >50% reduction in seizure frequency.
Many patients with cryptogenic epilepsy are refractory to AED and significant percent of cryptogenic epilepsy harbor neural autoantibody. In those cases, immunotherapy is suggestive based on favorable outcome of immunotherapy in autoimmune encephalitis and autoimmune epilepsy. Investigators aim to investigate the response to immunotherapy in intractable cryptogenic epilepsy patients with neural autoantibodies.
- Conditions
- Epilepsy, Unspecified, Intractable
- Being tested
- IVIG, Prednisolone
- Keywords
- Intractable cryptogenic epilepsy with autoimmune antibody, Immunotherapy
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVIGOther
IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)
PrednisoloneDrug
IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy | Experimental | Intravenous immunoglobulin (IVIG) and oral prednisolone. IVIG and oral prednisolone are administered simultaneously: IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day). Receives: Other: IVIG; Drug: Prednisolone |
| Control | No intervention | No immunotherapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent seizure reduction
Measured: 3 months
Secondary outcomes (7)
Seizure free rate
Measured: 3 months
Responder rate
Measured: 3 months
Treatment failure rate
Measured: 3 months
Quality of life scores as measured by QOLIE-31
Measured: 3 months
Quality of life scores as measured by BDI-2
Measured: 3 months
Cognition scores as measured by K-MMSE
Measured: 3 months
Amount of epileptiform discharge measured by EEG
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study startSep 2015
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Epilepsy, Unspecified, IntractableStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sang Kun Lee, Seoul National University Hospital
- Investigators
- Sang Kun Lee, Professor, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02695797
- Sponsor's protocol ID
- 1504102666
- Status last verified
- Feb 2016
- First submitted
- 18 Jun 2015
- Last updated
- 1 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Shorvon SD. The etiologic classification of epilepsy. Epilepsia. 2011 Jun;52(6):1052-7. doi: 10.1111/j.1528-1167.2011.03041.x. Epub 2011 Mar 30.
PubMed 21449936Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008 Apr;7(4):327-40. doi: 10.1016/S1474-4422(08)70060-7.
PubMed 18339348Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014 Jun;16(6):771-8. doi: 10.1093/neuonc/nou030. Epub 2014 Mar 16.
PubMed 24637228Shin YW, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Kim TJ, Lee KJ, Kim YS, Park KI, Jung KH, Lee SK, Chu K. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013 Dec 15;265(1-2):75-81. doi: 10.1016/j.jneuroim.2013.10.005. Epub 2013 Oct 17.
PubMed 24176648Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.
PubMed 23290630Lim JA, Lee ST, Jung KH, Kim S, Shin JW, Moon J, Byun JI, Kim TJ, Shin YW, Lee KJ, Kim YS, Park KI, Lee SK, Chu K. Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol. 2014 Apr;10(2):157-61. doi: 10.3988/jcn.2014.10.2.157. Epub 2014 Apr 23.
PubMed 24829602Kim TJ, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Shin YW, Lee KJ, Jung KH, Kim YS, Park KI, Chu K, Lee SK. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol. 2014 May 15;270(1-2):45-50. doi: 10.1016/j.jneuroim.2014.02.011. Epub 2014 Feb 28.
PubMed 24662003Barajas RF, Collins DE, Cha S, Geschwind MD. Adult-onset drug-refractory seizure disorder associated with anti-voltage-gated potassium-channel antibody. Epilepsia. 2010 Mar;51(3):473-7. doi: 10.1111/j.1528-1167.2009.02287.x. Epub 2009 Sep 22.
PubMed 19780798Majoie HJ, de Baets M, Renier W, Lang B, Vincent A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res. 2006 Oct;71(2-3):135-41. doi: 10.1016/j.eplepsyres.2006.06.003. Epub 2006 Jul 25.
PubMed 16870397Liimatainen S, Peltola M, Sabater L, Fallah M, Kharazmi E, Haapala AM, Dastidar P, Knip M, Saiz A, Peltola J. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia. 2010 May;51(5):760-7. doi: 10.1111/j.1528-1167.2009.02325.x. Epub 2009 Oct 8.
PubMed 19817821Peltola J, Kulmala P, Isojarvi J, Saiz A, Latvala K, Palmio J, Savola K, Knip M, Keranen T, Graus F. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology. 2000 Jul 12;55(1):46-50. doi: 10.1212/wnl.55.1.46.
PubMed 10891904Bien CG. Value of autoantibodies for prediction of treatment response in patients with autoimmune epilepsy: review of the literature and suggestions for clinical management. Epilepsia. 2013 May;54 Suppl 2:48-55. doi: 10.1111/epi.12184.
PubMed 23646971Toledano M, Britton JW, McKeon A, Shin C, Lennon VA, Quek AM, So E, Worrell GA, Cascino GD, Klein CJ, Lagerlund TD, Wirrell EC, Nickels KC, Pittock SJ. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology. 2014 May 6;82(18):1578-86. doi: 10.1212/WNL.0000000000000383. Epub 2014 Apr 4.
PubMed 24706013Brenner T, Sills GJ, Hart Y, Howell S, Waters P, Brodie MJ, Vincent A, Lang B. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia. 2013 Jun;54(6):1028-35. doi: 10.1111/epi.12127. Epub 2013 Mar 6.
PubMed 23464826Iorio R, Assenza G, Tombini M, Colicchio G, Della Marca G, Benvenga A, Damato V, Rossini PM, Vollono C, Plantone D, Marti A, Batocchi AP, Evoli A. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. Eur J Neurol. 2015 Jan;22(1):70-8. doi: 10.1111/ene.12529. Epub 2014 Aug 12.
PubMed 25112548
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody
- ClinicalTrials.gov ID
- NCT02695797
- Acronym / sponsor ID
- 1504102666
- Conditions
- Epilepsy, Unspecified, Intractable
- Keywords
- Intractable cryptogenic epilepsy with autoimmune antibody, Immunotherapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 1 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to investigate effect of immunotherapy in intractable cryptogenic epilepsy patients with autoimmune antibody.
Detailed description
Cryptogenic epilepsy is an epilepsy of presumed symptomatic nature but the cause has not been identified. It account for at least 40% of adult-onset epilepsy. Autoimmune encephalitis including classic paraneoplastic syndrome and autoimmune synaptic encephalitis is a new category of immune-mediated disorders which often has favorable outcome. Recent studies reported that immunotherapy improves seizure outcome in medically intractable epilepsy patients with clinical and serological evidence of an autoimmune basis. Neural autoantibodies were detected in 22% of epilepsy due to unknown cause in a study, mostly from the antiepileptic drug(AED)-resistant epilepsy group. Of the patients who received immunotherapy, 75% archived >50% reduction in seizure frequency.
Many patients with cryptogenic epilepsy are refractory to AED and significant percent of cryptogenic epilepsy harbor neural autoantibody. In those cases, immunotherapy is suggestive based on favorable outcome of immunotherapy in autoimmune encephalitis and autoimmune epilepsy. Investigators aim to investigate the response to immunotherapy in intractable cryptogenic epilepsy patients with neural autoantibodies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy | Experimental | Other: IVIG, Drug: PrednisoloneIntravenous immunoglobulin (IVIG) and oral prednisolone. IVIG and oral prednisolone are administered simultaneously: IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day). |
| Control | No intervention | –No immunotherapy. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A diagnosis of cryptogenic epilepsy according to the International League Against Epilepsy's Classification of Epilepsy.
- Intractable epilepsy: Complete seizure control is not achieved with trials of two appropriate antiepileptic drugs
- At least 1 seizure within the past 8 weeks
- Presence of autoimmune antibody (NMDAR, LGI1, CASPR2, AMPA1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/CRMP5, -amphiphysin, GAD) in serum or cerebrospinal fluid
- Written informed consent signed by the subject or legal guardian prior to entering the study
Key exclusion criteria (10 listed)
- Clinical evidence of autoimmune encephalitis such as autoimmune limbic encephalitis
- History of severe head trauma
- Presence of structural abnormality which is thought to be epileptogenic in brain MRI
- Epilepsy of predominantly genetic or presumed genetic origin
- An active CNS infection, demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results History of immunotherapy
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 |
|---|---|---|
| IVIGIVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day) | Other | Immunotherapy |
| PrednisoloneIVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day) | Drug | Immunotherapy |
Primary outcome
Percent seizure reduction
Time frame: 3 months
7 secondary outcomes
Seizure free rate
Time frame: 3 months
Responder rate
Time frame: 3 months
Treatment failure rate
Time frame: 3 months
Quality of life scores as measured by QOLIE-31
Time frame: 3 months
Quality of life scores as measured by BDI-2
Time frame: 3 months
Cognition scores as measured by K-MMSE
Time frame: 3 months
Amount of epileptiform discharge measured by EEG
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2016.
- Background: PubMed 21449936Shorvon SD. The etiologic classification of epilepsy. Epilepsia. 2011 Jun;52(6):1052-7. doi: 10.1111/j.1528-1167.2011.03041.x. Epub 2011 Mar 30.
- Background: PubMed 18339348Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008 Apr;7(4):327-40. doi: 10.1016/S1474-4422(08)70060-7.
- Background: PubMed 24637228Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014 Jun;16(6):771-8. doi: 10.1093/neuonc/nou030. Epub 2014 Mar 16.
- Background: PubMed 24176648Shin YW, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Kim TJ, Lee KJ, Kim YS, Park KI, Jung KH, Lee SK, Chu K. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013 Dec 15;265(1-2):75-81. doi: 10.1016/j.jneuroim.2013.10.005. Epub 2013 Oct 17.
- Background: PubMed 23290630Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.
- Background: PubMed 24829602Lim JA, Lee ST, Jung KH, Kim S, Shin JW, Moon J, Byun JI, Kim TJ, Shin YW, Lee KJ, Kim YS, Park KI, Lee SK, Chu K. Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol. 2014 Apr;10(2):157-61. doi: 10.3988/jcn.2014.10.2.157. Epub 2014 Apr 23.
- Background: PubMed 24662003Kim TJ, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Shin YW, Lee KJ, Jung KH, Kim YS, Park KI, Chu K, Lee SK. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol. 2014 May 15;270(1-2):45-50. doi: 10.1016/j.jneuroim.2014.02.011. Epub 2014 Feb 28.
- Background: PubMed 19780798Barajas RF, Collins DE, Cha S, Geschwind MD. Adult-onset drug-refractory seizure disorder associated with anti-voltage-gated potassium-channel antibody. Epilepsia. 2010 Mar;51(3):473-7. doi: 10.1111/j.1528-1167.2009.02287.x. Epub 2009 Sep 22.
- Background: PubMed 16870397Majoie HJ, de Baets M, Renier W, Lang B, Vincent A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res. 2006 Oct;71(2-3):135-41. doi: 10.1016/j.eplepsyres.2006.06.003. Epub 2006 Jul 25.
- Background: PubMed 19817821Liimatainen S, Peltola M, Sabater L, Fallah M, Kharazmi E, Haapala AM, Dastidar P, Knip M, Saiz A, Peltola J. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia. 2010 May;51(5):760-7. doi: 10.1111/j.1528-1167.2009.02325.x. Epub 2009 Oct 8.
- Background: PubMed 10891904Peltola J, Kulmala P, Isojarvi J, Saiz A, Latvala K, Palmio J, Savola K, Knip M, Keranen T, Graus F. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology. 2000 Jul 12;55(1):46-50. doi: 10.1212/wnl.55.1.46.
- Background: PubMed 23646971Bien CG. Value of autoantibodies for prediction of treatment response in patients with autoimmune epilepsy: review of the literature and suggestions for clinical management. Epilepsia. 2013 May;54 Suppl 2:48-55. doi: 10.1111/epi.12184.
- Individual participant dataSharing planned: No
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.
Kon Chu, Professor contact
Jung-Ah Lim, Fellow contact
Sang Kun Lee, Professor principal investigator
Seoul National University Hospital
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 IVIG and Prednisolone in people with Epilepsy, Unspecified, Intractable, run by Seoul National University Hospital at 1 site in South Korea.
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 5 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 1 Mar 2016. 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 South Korea. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kon Chu, Professor (stemcell.snu@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent seizure reduction (time frame: 3 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 NCT02695797, which also lists 15 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 1 Mar 2016; AzTrials last refreshed its copy on 6 Nov 2026.