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Pilot Study of alpha1-antitrypsin to Treat Neuromyelitis Optica Relapses (A1AT for NMO)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified March 2014 by Stanford University.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
Alexandra Goodyear, Stanford University Identifier:
First received: March 11, 2014
Last updated: March 12, 2014
Last verified: March 2014
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.

Condition Intervention Phase
Neuromyelitis Optica
Drug: Alpha1-antitrypsin
Drug: methylprednisolone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Center Open Label Pilot Study of Alpha1-Antitrypsin: A Novel Treatment to Mitigate Neuromyelitis Optica Attacks

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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. ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • Suicidality as a Measure of Safety and Tolerability [ Time Frame: Screening, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24. ]
    Columbia Classification Algorithm for Suicide Assessment (C-SSRS).

  • Serum biomarkers, including cytokines, elastase level, A1AT level, neutrophil elastase activity. [ Time Frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24. ]
  • Cerebral Spinal Fluid (CSF) biomarkers, including neurofilament, GFAP, MBP, neutrophil elastase activity, A1AT level, cytokines. [ Time Frame: Baseline and Week 8 ]
    Lumbar puncture.

  • Quality of life as a Measure of Safety and Tolerability [ Time Frame: Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24. ]
    Functional Assessment of Multiple Sclerosis Quality of Life instrument (FAMS).

  • Electrocardiogram (ECG) as a Measure of Safety and Tolerability [ Time Frame: Baseline, Day 2, and Week 16. ]
  • Urinalysis as a Measure of Safety and Tolerability [ Time Frame: Baseline, Day 2, and Week 16. ]

Estimated Enrollment: 5
Study Start Date: March 2014
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1AT
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.
Drug: Alpha1-antitrypsin
Other Names:
  • alpha1-proteinase inhibitor
Drug: methylprednisolone
3-5 days 1000mg IV methylprednisolone at first presentation with acute attack.
Other Name: Solu-Medrol
Active Comparator: Standard of care
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.
Drug: methylprednisolone
3-5 days 1000mg IV methylprednisolone at first presentation with acute attack.
Other Name: Solu-Medrol


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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).
  • 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.
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Please refer to this study by its identifier: NCT02087813

Contact: Angela Campbell 650-721-6188

United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Angela Campbell    650-721-6188   
Principal Investigator: Alexandra L Goodyear, MD, MS         
Sponsors and Collaborators
Stanford University
Principal Investigator: Alexandra L Goodyear, MD, MS Stanford University
  More Information

Responsible Party: Alexandra Goodyear, Assistant Professor, Stanford University Identifier: NCT02087813     History of Changes
Other Study ID Numbers: IRB-27176
Study First Received: March 11, 2014
Last Updated: March 12, 2014

Keywords provided by Stanford University:
neuromyelitis optica
optic neuritis
longitudinally extensive transverse myelitis

Additional relevant MeSH terms:
Myelitis, Transverse
Neuromyelitis Optica
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents processed this record on May 25, 2017