Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Randomized Controlled Trial Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- Best corrected visual acuity
研究概览
简要总结
Study Title: A National, Multicenter, Randomized Controlled Trial of the Modified Zipper Therapy in AQP4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (ELITE Study)
Brief Summary:
The goal of this clinical trial is to evaluate the efficacy and safety of a novel sequential immunomodulation strategy, termed "Modified Zipper Therapy," in patients with acute attacks of Aquaporin-4 antibody-positive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD). The therapy aims to enhance neurological recovery by combining plasma exchange (PE) with immediate complement inhibition using eculizumab, following high-dose corticosteroid pulse therapy.
The main questions this trial aims to answer are:
Efficacy: Does the Modified Zipper Therapy (high-dose corticosteroids + plasma exchange + eculizumab) lead to a higher rate of neurological improvement at Week 12 compared to standard therapy (high-dose corticosteroids + plasma exchange alone)?
For patients with NMOSD-related optic neuritis (NMOSD-ON), improvement is defined as a gain of ≥10 letters on the ETDRS chart or a decrease of ≥0.2 LogMAR in best-corrected visual acuity (BCVA).
For patients with NMOSD-related longitudinally extensive transverse myelitis (NMOSD-LETM), improvement is defined as a reduction of ≥2 points on the Expanded Disability Status Scale (EDSS).
Safety: What is the nature and frequency of adverse events experienced by participants receiving the Modified Zipper Therapy compared to those receiving standard therapy?
Researchers will compare the Modified Zipper Therapy group to the Standard Therapy group to see if the novel combination is more effective in improving visual and functional outcomes in acute AQP4-IgG+ NMOSD.
Participants will:
Be randomly assigned (like a coin toss) to receive either the Modified Zipper Therapy or the Standard Therapy.
Undergo a treatment period involving intravenous corticosteroids and a series of plasma exchange sessions. The Modified Zipper Therapy group will also receive intravenous eculizumab infusions timed around the plasma exchange procedures.
Be followed for 24 weeks after treatment completion.
Attend scheduled clinic visits for comprehensive assessments including:
Visual acuity testing (using ETDRS, Snellen, and low-contrast charts).
Neurological function evaluations (EDSS and OSIS scores).
Optical coherence tomography (OCT) and visual evoked potential (VEP) tests.
Magnetic resonance imaging (MRI) scans of the optic nerves.
Safety monitoring (physical exams, lab tests, ECGs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants ≥ 18 years of age
- •Definite diagnosis according to the 2015 IPND diagnostic criteria for AQP4-IgG-positive NMOSD
- •Seropositivity for anti-AQP4 antibody.
- •Time from onset to enrollment ≤ 30 days.
- •For patients with optic neuritis: visual acuity ≤ 20/200 at screening; for relapse cases, baseline visual acuity prior to this acute episode must have been ≥ 20/
- •For patients with longitudinal extensive transverse myelitis (LETM): EDSS score ≥ 5.5 at screening; for relapse cases, baseline EDSS score prior to this acute episode must have been ≤ 3.
- •Ability to understand and voluntarily provide written informed consent-
排除标准
- •Patients with concurrent neuromuscular disorders.
- •Patients with severe coagulation dysfunction.
- •Patients with known allergy to plasma or intravenous immunoglobulin (IVIG).
- •Patients with active hepatitis B or C virus infection, human immunodeficiency virus (HIV) infection, or those deemed at high risk for the onset or reactivation of syphilis or tuberculosis at screening.
- •Patients with active systemic infection at screening, or a history of severe chronic or recurrent infections.
- •Pregnant or lactating patients.
- •Patients with chronic, severe medical conditions that may affect study compliance.
- •Patients with any clinically significant abnormal laboratory findings as determined by the investigator (e.g., severe anemia, leukopenia, thrombocytopenia, etc.).
- •Patients whom the investigator considers unlikely to complete the study or unlikely to comply with the study requirements (for administrative reasons or otherwise).
研究组 & 干预措施
Experimental group
干预措施: Eculizumab administration (Biological)
Experimental group
干预措施: High-dose corticosteroid pulse therapy (Drug)
Experimental group
干预措施: Plasma exchange (PE) (Procedure)
Control group
High-dose corticosteroid pulse therapy+ plasma exchange
干预措施: High-dose corticosteroid pulse therapy (Drug)
Control group
High-dose corticosteroid pulse therapy+ plasma exchange
干预措施: Plasma exchange (PE) (Procedure)
结局指标
主要结局
Best corrected visual acuity
时间窗: Baseline, Week 12
Expanded Disability Status Scale (EDSS)
时间窗: Baseline, Week 12
The Expanded Disability Status Scale (EDSS) is an ordinal scale ranging from 0 to 10, with higher scores indicating worse neurological impairment and disability in patients with neuromyelitis optica spectrum disorder (NMOSD)
次要结局
- Best corrected visual acuity(Baseline, Week 4, Week 24,)
- Concentration of serum sC5b-9(Baseline, Week 4, Week 12, Week 24)
- Expanded Disability Status Scale (EDSS)(Baseline, Week 4, Week 24,)
- Optic-Spinal Impairment Score(OSIS)(Baseline, Week 4, Week 12, Week 24)
- Visual Evoked Potential P100 Wave Latency(Baseline, Week 12, Week 24)
- Visual Evoked Potential P100 Wave Amplitude(Baseline, Week 12, Week 24)
- Retinal nerve fiber layer (RNFL) thickness(Baseline, Week 12, Week 24,)
- Ganglion Cell-Inner Plexiform Layer (GCIPL) Thickness(Baseline, Week 12, Week 24)
- Cross-sectional area of the optic nerve(Baseline, Week 12, Week 24)
- Length of Optic Nerve Lesion(Baseline, Week 12, Week 24)
研究者
Chao Zhang
Professor
Tianjin Medical University General Hospital