Infantile Neronal Ceroid LipofuscinosisPhase 4NCT00028262
Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis
A Phase 4 study testing Cystagon in people with Infantile Neronal Ceroid Lipofuscinosis, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This study will examine the effectiveness of a drug called Cystagon in treating infantile neuronal ceroid lipofuscinosis (INCL), a progressive neurological disease affecting children. Read more about this study
- Who is it for?
- Ages 6 months to 3 years
- Conditions the study is for
- Infantile Neronal Ceroid Lipofuscinosis
- What is being tested?
- Cystagon
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Nov 2013
- 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 6 months to 3 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Only patients between 6 months and 3 years of age will be admitted in this study. Parents or caregivers of patients recruited to the study will be provided with a copy of the protocol and the consent form to review prior to their coming to the NIH. They will be encouraged to call either Dr. Levin or Dr. Mukherjee to discuss any questions they may have concerning the protocol prior to enrollment in the study.
- The proposed age range (6 mo to 3 yrs) was chosen because these children are expected to have a mild to moderate neurological deficiency but are well enough to be cared for at home by the family. Therefore, these patients should not require extensive medical or nursing care during their stay at the Clinical Center. Moreover, the patients are locally cared for by neurologists and pediatricians on a regular basis, and such care will continue when the patients return home.
- The rigid age exclusion criteria will be used because the majority of INCL patients have more frequent seizures, complete retinal blindness and significant cerebral atrophy beyond 3 years of age. Dr. Santavuori (one of our consultants who is now deceased), who had the most extensive experience with these patients, believed that the neurological degeneration after age 2 might not be reversible. While Dr. Santavuori s speculation is well taken, we feel that since to date there has not been any effective treatment to slow the progression of neuronal death in INCL, and since our preliminary results show that Cystagon slows the progression of neurodegeneration, we feel that a combination of Cystagon plus N-Ac with its anti-apoptotic and neuro-protective effects may show some added benefits over Cystagon therapy alone.
- In our initial protocol we restricted the admission of patients that carried two lethal mutations in the PPT1 gene. The purpose of including only those patients who carry specific PPT1 mutations
- (L10X, R151X, R164X, W296X, R122W, c.169insA and E184K) was to establish that the beneficial effects of the combination therapy because a patients who had any two of these mutations manifested the most severe disease phenotype. Because of the uniform manifestation of the disease it was easier to determine any beneficial effects of the combination drug therapy.
- Subsequently, our protocol was approved for treatment of INCL patients with any two mutations in the PPT1 gene. Our protocol has been previously amended to include all INCL patients regardless of the PPT1 mutations they carry.
- Patients with intractable seizures that cannot be controlled by two or fewer antiepileptic medications will not be accepted for this study. Patients who cannot take nourishment orally or who are in a vegetative state will not be enrolled in this study even if the 6 months to 3 year age criterion is met.
- Both male and female patients are eligible for enrollment in this study.
Who cannot join
None listed.
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: A Combination Therapy With Cystagon and N-Acetylcysteine for INCL Patients
This study will examine the effectiveness of a drug called Cystagon in treating infantile neuronal ceroid lipofuscinosis (INCL), a progressive neurological disease affecting children. At around 11 to 13 months of age, patients develop slowed head growth, mild brain atrophy (wasting), electroencephalographic (EEG) changes and retinal deterioration, with symptoms worsening over time. The disease results from an enzyme deficiency that causes fatty compounds called ceroid to accumulate in cells. In laboratory experiments, Cystagon has helped remove ceroid from cells of patients with INCL.
Children with INCL between 6 months and 3 years of age may be eligible for this study. Participants take Cystagon daily by mouth every 6 hours. They are admitted to the NIH Clinical Center for a 4- to 5-day period every 6 months for the following tests and evaluations:
Read more
- Review of medical history, including a detailed record of seizures, physical examination, blood tests and clinical photographs. For the initial baseline studies, examinations may also be scheduled with pediatric neurology, ophthalmology and anesthesia services.
- Magnetic resonance imaging (MRI) of the brain MRI uses a powerful magnet, radio waves, and computers to provide detailed images of the brain without the use of X-rays. The patient lies on a table that slides inside a donut-shaped machine containing a magnetic field. The child requires general anesthesia for the procedure.
- Electroretinogram (ERG) measures the function of the retina, the light-sensitive tissue in the back of the eye. To record the flash ERG, a special contact lens is placed on the eye s surface and the eye is stimulated with flashes of light. Infants and very young children require general anesthesia for the procedure.
- Visual evoked potential (VEP) measures the function of the visual pathway from the eye to the brain. To record the VEP, five electrodes are placed on the scalp and the eye is stimulated with flashes of light. Infants and very young children must be anesthetized for the procedure.
- Electroencephalogram (EEG) measures brain electrical activity, using electrodes placed on the scalp. The test is useful in defining seizures. The child may need to be sedated to keep still during the test.
- Skin biopsy A small piece of skin is removed (usually from the upper arm or shoulder) under local anesthetic to grow cells in the laboratory. This procedure is done at the start of the study and is repeated after 1 year if therapy results are promising.
Children s condition may improve, stabilize or worsen during this study. Life may be prolonged without significant improvement in quality. The information gained from the study may help scientists develop more potent drugs to treat INCL.
Read the detailed description
Neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, represent a group of the most common (1 in 12,500) heritable neurodegenerative storage disorders of childhood. Mutations of at least 8 different genes are responsible for various forms of NCL. The infantile form of NCL or INCL is the most severe disease. It is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 is a lysosomal enzyme that cleaves thioester linkages in S-acylated proteins and its deficiency leads to abnormal lysosomal accumulation of fattyacylated- proteins (ceroids) leading to INCL pathogenesis. Since thioester linkages are labile, drugs with nucleophilic property are likely to mimic PPT1 and may have therapeutic potential for INCL. We previously reported that cysteamine, phosphocysteamine, cysteamine bitartrate (cystagon) and N-acetylcysteine disrupt thioester linkages in a model PPT1-substrate, C(14) palmitoyl-CoA, releasing C(14) palmitic acid. The results of our laboratory studies have shown that cysteamine mediates the depletion of intracellular ceroid deposits and prevents their reaccumulation. For the last 9 years, we have been conducting a clinical trial to determine whether a combination of Cystagon (Cysteamine bitartrate) and N-acetylcysteine (mucomyst) is beneficial for INCL patients. In parallel with these studies, using an animal model of INCL we found that this combination therapy reduces oxidative stress caused by high levels of reactive oxygen species (ROS) in the brain of mice lacking the PPT1 enzyme. To date, we have admitted a total of 10 patients (5 females and 5 males) to this protocol; however, one male patient was lost to follow-up. Thus, we have treated 9 patients (5 females and 4 males) and these patients showed no adverse reactions to these drugs except for one patient who initially had mild gastrointestinal discomfort which went away when cystagon was stopped and restarted from the lowest dose and this mild adverse effect did not recur. Compared with the published natural history of INCL, our preliminary results show that although several parameters of disease progression are slowed due to the treatment it does not completely arrest the neurodegenerative process. We are currently analyzing all the data gathered so far and a manuscript describing the results will be prepared for submission to a peer-reviewed journal.
- Conditions
- Infantile Neronal Ceroid Lipofuscinosis
- Being tested
- Cystagon
- Keywords
- Palmitoyl-Protein Thioesterase, Lysosomes, Batten Disease, Encephalopathy, Progressive Neurodegeneration, CLN 1, Infantile Neuronal Ceroid Lipofuscinosis, Cystagon
- Medical subject headings
- Ceroid lipofuscinosis, neuronal 1, infantile, Neuronal Ceroid-Lipofuscinoses, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CystagonDrug
| Study group | Role | What they receive |
|---|---|---|
| Drug: Cystagon and N-acetylcysteine | Experimental | Not described Receives: Drug: Cystagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells.
The GRODs in peripheral white blood cells from all patients before and during treatment were analyzed by transmission electron microscopy (TEM) at 30000xmagnification. Two investigators working independently of each other identified and counted the GRODs and the results were averaged.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2001 (estimated)
- Study startFeb 2001
- Primary completionNov 2013
- Study completionNov 2013
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 (5)Papers the sponsor has linked to this study.
- Other trials for Infantile Neronal Ceroid LipofuscinosisStudies of the same condition, open and under way.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Anil B Mukherjee, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028262
- Sponsor's protocol ID
- 010086
- Other IDs
- 01-CH-0086
- Status last verified
- Sep 2016
- First submitted
- 17 Dec 2001
- Last updated
- 27 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Santavuori P. Neuronal ceroid-lipofuscinoses in childhood. Brain Dev. 1988;10(2):80-3. doi: 10.1016/s0387-7604(88)80075-5.
PubMed 3291628Rider JA, Rider DL. Batten disease: past, present, and future. Am J Med Genet Suppl. 1988;5:21-6. doi: 10.1002/ajmg.1320310606.
PubMed 3146319Rapola J, Haltia M. Cytoplasmic inclusions in the vermiform appendix and skeletal muscle in two types of so-called neuronal ceroid-lipofuscinosis. Brain. 1973 Dec;96(4):833-40. doi: 10.1093/brain/96.4.833. No abstract available.
PubMed 4359377Zhang Z, Butler JD, Levin SW, Wisniewski KE, Brooks SS, Mukherjee AB. Lysosomal ceroid depletion by drugs: therapeutic implications for a hereditary neurodegenerative disease of childhood. Nat Med. 2001 Apr;7(4):478-84. doi: 10.1038/86554.
PubMed 11283676Levin SW, Baker EH, Zein WM, Zhang Z, Quezado ZM, Miao N, Gropman A, Griffin KJ, Bianconi S, Chandra G, Khan OI, Caruso RC, Liu A, Mukherjee AB. Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study. Lancet Neurol. 2014 Aug;13(8):777-87. doi: 10.1016/S1474-4422(14)70142-5. Epub 2014 Jul 2.
PubMed 24997880
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combination Therapy With Cystagon and N-Acetylcysteine for INCL Patients
- ClinicalTrials.gov ID
- NCT00028262
- Acronym / sponsor ID
- 010086
- Conditions
- Infantile Neronal Ceroid Lipofuscinosis
- Keywords
- Palmitoyl-Protein Thioesterase, Lysosomes, Batten Disease, Encephalopathy, Progressive Neurodegeneration, CLN 1, Infantile Neuronal Ceroid Lipofuscinosis, Cystagon
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Feb 2001
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 18 Dec 2001 (estimated)
- Results
- Posted 21 Jan 2015
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 effectiveness of a drug called Cystagon in treating infantile neuronal ceroid lipofuscinosis (INCL), a progressive neurological disease affecting children. At around 11 to 13 months of age, patients develop slowed head growth, mild brain atrophy (wasting), electroencephalographic (EEG) changes and retinal deterioration, with symptoms worsening over time. The disease results from an enzyme deficiency that causes fatty compounds called ceroid to accumulate in cells. In laboratory experiments, Cystagon has helped remove ceroid from cells of patients with INCL.
Children with INCL between 6 months and 3 years of age may be eligible for this study. Participants take Cystagon daily by mouth every 6 hours. They are admitted to the NIH Clinical Center for a 4- to 5-day period every 6 months for the following tests and evaluations:
- Review of medical history, including a detailed record of seizures, physical examination, blood tests and clinical photographs. For the initial baseline studies, examinations may also be scheduled with pediatric neurology, ophthalmology and anesthesia services.
- Magnetic resonance imaging (MRI) of the brain MRI uses a powerful magnet, radio waves, and computers to provide detailed images of the brain without the use of X-rays. The patient lies on a table that slides inside a donut-shaped machine containing a magnetic field. The child requires general anesthesia for the procedure.
- Electroretinogram (ERG) measures the function of the retina, the light-sensitive tissue in the back of the eye. To record the flash ERG, a special contact lens is placed on the eye s surface and the eye is stimulated with flashes of light. Infants and very young children require general anesthesia for the procedure.
- Visual evoked potential (VEP) measures the function of the visual pathway from the eye to the brain. To record the VEP, five electrodes are placed on the scalp and the eye is stimulated with flashes of light. Infants and very young children must be anesthetized for the procedure.
- Electroencephalogram (EEG) measures brain electrical activity, using electrodes placed on the scalp. The test is useful in defining seizures. The child may need to be sedated to keep still during the test.
- Skin biopsy A small piece of skin is removed (usually from the upper arm or shoulder) under local anesthetic to grow cells in the laboratory. This procedure is done at the start of the study and is repeated after 1 year if therapy results are promising.
Children s condition may improve, stabilize or worsen during this study. Life may be prolonged without significant improvement in quality. The information gained from the study may help scientists develop more potent drugs to treat INCL.
Detailed description
Neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, represent a group of the most common (1 in 12,500) heritable neurodegenerative storage disorders of childhood. Mutations of at least 8 different genes are responsible for various forms of NCL. The infantile form of NCL or INCL is the most severe disease. It is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 is a lysosomal enzyme that cleaves thioester linkages in S-acylated proteins and its deficiency leads to abnormal lysosomal accumulation of fattyacylated- proteins (ceroids) leading to INCL pathogenesis. Since thioester linkages are labile, drugs with nucleophilic property are likely to mimic PPT1 and may have therapeutic potential for INCL. We previously reported that cysteamine, phosphocysteamine, cysteamine bitartrate (cystagon) and N-acetylcysteine disrupt thioester linkages in a model PPT1-substrate, C(14) palmitoyl-CoA, releasing C(14) palmitic acid. The results of our laboratory studies have shown that cysteamine mediates the depletion of intracellular ceroid deposits and prevents their reaccumulation. For the last 9 years, we have been conducting a clinical trial to determine whether a combination of Cystagon (Cysteamine bitartrate) and N-acetylcysteine (mucomyst) is beneficial for INCL patients. In parallel with these studies, using an animal model of INCL we found that this combination therapy reduces oxidative stress caused by high levels of reactive oxygen species (ROS) in the brain of mice lacking the PPT1 enzyme. To date, we have admitted a total of 10 patients (5 females and 5 males) to this protocol; however, one male patient was lost to follow-up. Thus, we have treated 9 patients (5 females and 4 males) and these patients showed no adverse reactions to these drugs except for one patient who initially had mild gastrointestinal discomfort which went away when cystagon was stopped and restarted from the lowest dose and this mild adverse effect did not recur. Compared with the published natural history of INCL, our preliminary results show that although several parameters of disease progression are slowed due to the treatment it does not completely arrest the neurodegenerative process. We are currently analyzing all the data gathered so far and a manuscript describing the results will be prepared for submission to a peer-reviewed journal.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug: Cystagon and N-acetylcysteine | Experimental | Drug: Cystagon |
Who may qualify
- Ages
- 6 months to 3 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Only patients between 6 months and 3 years of age will be admitted in this study. Parents or caregivers of patients recruited to the study will be provided with a copy of the protocol and the consent form to review prior to their coming to the NIH. They will be encouraged to call either Dr. Levin or Dr. Mukherjee to discuss any questions they may have concerning the protocol prior to enrollment in the study.
- The proposed age range (6 mo to 3 yrs) was chosen because these children are expected to have a mild to moderate neurological deficiency but are well enough to be cared for at home by the family. Therefore, these patients should not require extensive medical or nursing care during their stay at the Clinical Center. Moreover, the patients are locally cared for by neurologists and pediatricians on a regular basis, and such care will continue when the patients return home.
- The rigid age exclusion criteria will be used because the majority of INCL patients have more frequent seizures, complete retinal blindness and significant cerebral atrophy beyond 3 years of age. Dr. Santavuori (one of our consultants who is now deceased), who had the most extensive experience with these patients, believed that the neurological degeneration after age 2 might not be reversible. While Dr. Santavuori s speculation is well taken, we feel that since to date there has not been any effective treatment to slow the progression of neuronal death in INCL, and since our preliminary results show that Cystagon slows the progression of neurodegeneration, we feel that a combination of Cystagon plus N-Ac with its anti-apoptotic and neuro-protective effects may show some added benefits over Cystagon therapy alone.
- In our initial protocol we restricted the admission of patients that carried two lethal mutations in the PPT1 gene. The purpose of including only those patients who carry specific PPT1 mutations
- (L10X, R151X, R164X, W296X, R122W, c.169insA and E184K) was to establish that the beneficial effects of the combination therapy because a patients who had any two of these mutations manifested the most severe disease phenotype. Because of the uniform manifestation of the disease it was easier to determine any beneficial effects of the combination drug therapy.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Cystagon | Drug | Drug: Cystagon and N-acetylcysteine |
Primary outcome
Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells.
Time frame: 10 years
The GRODs in peripheral white blood cells from all patients before and during treatment were analyzed by transmission electron microscopy (TEM) at 30000xmagnification. Two investigators working independently of each other identified and counted the GRODs and the results were averaged.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3291628Santavuori P. Neuronal ceroid-lipofuscinoses in childhood. Brain Dev. 1988;10(2):80-3. doi: 10.1016/s0387-7604(88)80075-5.
- Background: PubMed 3146319Rider JA, Rider DL. Batten disease: past, present, and future. Am J Med Genet Suppl. 1988;5:21-6. doi: 10.1002/ajmg.1320310606.
- Background: PubMed 4359377Rapola J, Haltia M. Cytoplasmic inclusions in the vermiform appendix and skeletal muscle in two types of so-called neuronal ceroid-lipofuscinosis. Brain. 1973 Dec;96(4):833-40. doi: 10.1093/brain/96.4.833. No abstract available.
- Background: PubMed 11283676Zhang Z, Butler JD, Levin SW, Wisniewski KE, Brooks SS, Mukherjee AB. Lysosomal ceroid depletion by drugs: therapeutic implications for a hereditary neurodegenerative disease of childhood. Nat Med. 2001 Apr;7(4):478-84. doi: 10.1038/86554.
- Results publication: PubMed 24997880Levin SW, Baker EH, Zein WM, Zhang Z, Quezado ZM, Miao N, Gropman A, Griffin KJ, Bianconi S, Chandra G, Khan OI, Caruso RC, Liu A, Mukherjee AB. Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study. Lancet Neurol. 2014 Aug;13(8):777-87. doi: 10.1016/S1474-4422(14)70142-5. Epub 2014 Jul 2.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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.
Anil B Mukherjee, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 Cystagon in people with Infantile Neronal Ceroid Lipofuscinosis, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 8 inclusion and 0 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 27 Oct 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 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 21 Jan 2015). 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 Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells. (time frame: 10 years). 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 NCT00028262, which also lists 5 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 27 Oct 2016.