Neuromyelitis OpticaPhase 1A1AT for NMONCT02087813
Pilot Study of alpha1-antitrypsin to Treat Neuromyelitis Optica Relapses
A Phase 1 study testing Alpha1-antitrypsin and methylprednisolone in people with Neuromyelitis Optica, run by Stanford University at 1 site in United States.
Trial summary
Neuromyelitis Optica (NMO) is a rare, devastating demyelinating disease of the central nervous system (CNS) that has different causes and treatments from the more common demyelinating disease multiple sclerosis (MS). Current NMO therapies are nonspecific and have varying and often suboptimal benefit. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuromyelitis Optica
- What is being tested?
- Alpha1-antitrypsin and methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Mar 2016
- Phase
- Phase 1
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written informed consent.
- Age ≥18 and ≤ 75 years.
- Diagnosis of NMO or NMO spectrum disorder (NMOSD). The diagnosis of NMO will conform to the 2006 Wingerchuk criteria.1, 2 The diagnosis of NMOSD will include patients with relapsing optic neuritis and aquaporin-4 antibody (AQP4) seropositivity or patients with relapsing longitudinally extensive transverse myelitis and AQP4 seropositivity.2-5 NMO and NMOSD will be collectively referred to as NMO.
- AQP4-antibody positivity.
- Present with an acute NMO attack (see definition below).
- Patients must not have a history of clinically significant infusion reactions with administration of biologic agents.
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- If on chronic treatment for NMO, treatment was initiated at least 3 months earlier and medication dose is stable. Additional restrictions will be placed on changes in concomitant symptomatic medications.
- A female subject of childbearing potential must have a negative serum pregnancy test at the screening visit and agree to use a medically reliable method of contraception (e.g., barrier with either spermicide or hormonal contraception) until study completion.
- Agree to answer the questions on the Columbia Suicide Severity Rating Scale at each specified visit.
Who cannot join
- A woman who is pregnant, breastfeeding, or planning pregnancy.
- If the patient is enrolled in any other experimental trial or on other experimental therapy.
- If the patient has a known IgA deficiency with IgA-antibodies.
- Any medical condition or clinically significant laboratory abnormality that in the Investigator's judgment may affect the patient's ability to safely complete the study.
- Acute attack:
- The occurrence of new or worsening neurological symptoms consistent with optic neuritis, transverse myelitis, or a brain lesion that develop acutely (i.e., patients must present within 7 days of symptom onset).
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- The symptoms must persist for at least 48 hours, are not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to concomitant medications).
- The symptoms must be accompanied by sensory, motor or visual acuity objective deficits, which must be verified by the examining physician.
- A single episode of a paroxysmal symptom (e.g., tonic spasm) is not a relapse; however, the new onset of multiple occurrences of a paroxysmal symptom over at least 48 hours can be a relapse if accompanied by a new, corresponding objective deficit.
- Sensory symptoms with no change on clinical examination, fatigue, mood change, or bladder or bowel urgency or incontinence will not be sufficient to establish a relapse.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Center Open Label Pilot Study of Alpha1-Antitrypsin: A Novel Treatment to Mitigate Neuromyelitis Optica Attacks
Neuromyelitis Optica (NMO) is a rare, devastating demyelinating disease of the central nervous system (CNS) that has different causes and treatments from the more common demyelinating disease multiple sclerosis (MS). Current NMO therapies are nonspecific and have varying and often suboptimal benefit. The investigators will evaluate whether use of alpha1-antitrypsin (A1AT, an FDA-approved medication for patients with congenital deficiency of A1AT associated with emphysema) can benefit acute attacks of NMO, improving patient disability and quality of life.
- Conditions
- Neuromyelitis Optica
- Being tested
- Alpha1-antitrypsin, methylprednisolone
- Keywords
- neuromyelitis optica, optic neuritis, longitudinally extensive transverse myelitis
- Medical subject headings
- Neuromyelitis Optica, Optic Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha1-antitrypsinDrug
Also called ARALAST NP, alpha1-proteinase inhibitor
Also called Solu-Medrol
3-5 days 1000mg IV methylprednisolone at first presentation with acute attack.
| Study group | Role | What they receive |
|---|---|---|
| A1AT | Experimental | Alpha1-antitrypsin 120mg/kg once weekly for a total of 4 doses, to be given intravenously. This will be given in addition to standard of care 3-5 days of 1000mg IV methylprednisolone. Receives: Drug: Alpha1-antitrypsin; Drug: methylprednisolone |
| Standard of care | Active comparator | Patients that do not wish to receive study treatment but agree to otherwise follow study protocol will also be enrolled in an observational cohort. They will receive the standard of care 3-5 days 1000mg IV methylprednisolone. Receives: Drug: methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in disability from baseline/nadir to week 24 as assessed by Opticospinal Impairment Score (OSIS) subscale.
Measured: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
Secondary outcomes (4)
Mean change in disability from baseline/nadir to week 24 as assessed by Expanded Disability Status Scale (EDSS).
Measured: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
For patients experiencing optic neuritis, mean change in visual acuity from baseline/nadir to week 24 as assessed by Sloan 2.5% low contrast visual acuity chart.
Measured: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
Mean change in retinal nerve fiber layer from baseline/nadir to week 24 as assessed by optical coherence tomography (OCT).
Measured: Baseline and Week 24
Mean change in length of spinal cord lesion from baseline/nadir to week 24 as assessed by magnetic resonance imaging (MRI) T2 sequences.
Measured: Baseline, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromyelitis OpticaStudies of the same condition, open and under way.
- More trials run by Stanford 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandra L Goodyear, MD, MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02087813
- Sponsor's protocol ID
- IRB-27176
- Acronym
- A1AT for NMO
- Status last verified
- Apr 2019
- First submitted
- 11 Mar 2014
- Last updated
- 12 Apr 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center Open Label Pilot Study of Alpha1-Antitrypsin: A Novel Treatment to Mitigate Neuromyelitis Optica Attacks
- ClinicalTrials.gov ID
- NCT02087813
- Acronym / sponsor ID
- A1AT for NMO / IRB-27176
- Conditions
- Neuromyelitis Optica
- Keywords
- neuromyelitis optica, optic neuritis, longitudinally extensive transverse myelitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Mar 2014 (actual)
- Primary completion
- Mar 2016 (estimated)
- First posted
- 14 Mar 2014 (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.
Neuromyelitis Optica (NMO) is a rare, devastating demyelinating disease of the central nervous system (CNS) that has different causes and treatments from the more common demyelinating disease multiple sclerosis (MS). Current NMO therapies are nonspecific and have varying and often suboptimal benefit. The investigators will evaluate whether use of alpha1-antitrypsin (A1AT, an FDA-approved medication for patients with congenital deficiency of A1AT associated with emphysema) can benefit acute attacks of NMO, improving patient disability and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A1AT | Experimental | Drug: Alpha1-antitrypsin, Drug: methylprednisoloneAlpha1-antitrypsin 120mg/kg once weekly for a total of 4 doses, to be given intravenously. This will be given in addition to standard of care 3-5 days of 1000mg IV methylprednisolone. |
| Standard of care | Active comparator | Drug: methylprednisolonePatients that do not wish to receive study treatment but agree to otherwise follow study protocol will also be enrolled in an observational cohort. They will receive the standard of care 3-5 days 1000mg IV methylprednisolone. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provide written informed consent.
- Age ≥18 and ≤ 75 years.
- Diagnosis of NMO or NMO spectrum disorder (NMOSD). The diagnosis of NMO will conform to the 2006 Wingerchuk criteria.1, 2 The diagnosis of NMOSD will include patients with relapsing optic neuritis and aquaporin-4 antibody (AQP4) seropositivity or patients with relapsing longitudinally extensive transverse myelitis and AQP4 seropositivity.2-5 NMO and NMOSD will be collectively referred to as NMO.
- AQP4-antibody positivity.
- Present with an acute NMO attack (see definition below).
Key exclusion criteria (10 listed)
- A woman who is pregnant, breastfeeding, or planning pregnancy.
- If the patient is enrolled in any other experimental trial or on other experimental therapy.
- If the patient has a known IgA deficiency with IgA-antibodies.
- Any medical condition or clinically significant laboratory abnormality that in the Investigator's judgment may affect the patient's ability to safely complete the study.
- The occurrence of new or worsening neurological symptoms consistent with optic neuritis, transverse myelitis, or a brain lesion that develop acutely (i.e., patients must present within 7 days of symptom onset).
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 |
|---|---|---|
| Alpha1-antitrypsinAlso: ARALAST NP, alpha1-proteinase inhibitor | Drug | A1AT |
| methylprednisoloneAlso: Solu-Medrol3-5 days 1000mg IV methylprednisolone at first presentation with acute attack. | Drug | A1AT, Standard of care |
Primary outcome
Mean change in disability from baseline/nadir to week 24 as assessed by Opticospinal Impairment Score (OSIS) subscale.
Time frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
4 secondary outcomes
Mean change in disability from baseline/nadir to week 24 as assessed by Expanded Disability Status Scale (EDSS).
Time frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
For patients experiencing optic neuritis, mean change in visual acuity from baseline/nadir to week 24 as assessed by Sloan 2.5% low contrast visual acuity chart.
Time frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.
Mean change in retinal nerve fiber layer from baseline/nadir to week 24 as assessed by optical coherence tomography (OCT).
Time frame: Baseline and Week 24
Mean change in length of spinal cord lesion from baseline/nadir to week 24 as assessed by magnetic resonance imaging (MRI) T2 sequences.
Time frame: Baseline, Week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
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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.
Alexandra L Goodyear, MD, MS principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alpha1-antitrypsin and methylprednisolone in people with Neuromyelitis Optica, run by Stanford 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 9 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: withdrawn, as of the sponsor's last update on 12 Apr 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Mean change in disability from baseline/nadir to week 24 as assessed by Opticospinal Impairment Score (OSIS) subscale. (time frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2019.