Low Dose IL-2 in the Treatment of Immune-associated ALS Syndrome
- Registration Number
- NCT04952155
- Lead Sponsor
- Peking University Third Hospital
- Brief Summary
The purpose of this study was to evaluate the efficacy and safety of low-dose IL-2 in the treatment of immunorelated ALS syndrome.
- Detailed Description
This is a single-center, open-label, self-controlled clinical study with a sample size of 10 patients for 48 weeks, including 24 weeks of administration, and 24 weeks of follow-up. During the administration period, medication was given for 2 weeks and rest for 2 weeks, as a course of treatment, with a total of 6 courses for 24 weeks. During the administration period, the drug was given on alternate days, and IL-2 1mIU was subcutaneously injected the next day for 7 times, and then rested for 2 weeks, and the cycle was repeated for 6 times. The primary outcome index was the change in the rate of ALSFRS-R score between administration period and follow-up period. Secondary outcome measures included changes in the rate of ALSAQ-40 score, ROADS score, MRC score, survival time, FVC%, Treg and CD4+ T cell subsets, inflammatory factors, serum and cerebrospinal fluid NFL during follow-up versus administration , changes in the inhibition function of Treg; Exploratory outcome indicators included the change degree of compound muscle action potential (CMAP) amplitude, quantitative analysis of corneal nerve morphologic changes by corneal confocal microscopy (CCM), Treg single-cell sequencing transcriptome analysis. The related safety indexes were also evaluated.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 13
- 18-70 years old;
- Clinically diagnosed with ALS syndrome, i.e., with ALS -like manifestations, consisting of a combination of upper and/or lower motor neuron damage;
- significant abnormalities with rheumatoid immune-related indicators, or diagnoses of immune-mediated ALS syndrome, including but not limited to multifocal motor neuropathy (MMN), Lewis-Sumner syndrome, and other ALS-like syndromes with an immune background that cannot be clearly classified;
- Poor treatment with conventional hormones or gamma globulin;
- Permitted concomitant treatment: oral prednisone or equivalent doses of other glucocorticoids (≤1.0mg/kg/d); Oral routine dose of immunosuppressants or immunomodulators, such as cyclophosphamide, tacrolimus, etc.; Routine oral doses such as too much force; Doses and types of accompanying therapeutic drugs should not be changed from the trial enrollment to the end of follow-up.
- For women of reproductive age, contraception for at least 2 weeks at the time of enrolment and negative urine HCG;
- Reasonable and effective contraceptive measures should be taken by subjects of childbearing age from the time of trial enrollment to the end of follow-up;
- Signed informed consent.
- Allergic or intolerance to IL2;
- Receive non-standard treatment or use of excessive dose of glucocorticoids or gamma globulin intravenously within 2 months before enrollment;
- Vaccination within 6 months before enrolment or between enrolment and the end of follow-up;
- Peripheral venous white blood cells < 2000/mm3, lymphocytes < 600/mm3, platelets < 80,000 /mm3;
- Complicated with severe infection or inflammation, such as bacteremia, sepsis, etc.;
- Complicated blood system diseases, infectious diseases (hepatitis, HIV, tuberculosis, etc.), mental diseases, dementia, severe hypotension, substance abuse history, malignant tumor history, organ transplantation history, etc.;
- Severe liver, kidney, lung or heart dysfunction: heart failure (≥NYHA grade III), renal insufficiency (creatinine clearance ≤30ml/min), abnormal liver function (3 times the upper limit of normal >);
- Pregnant and lactating women;
- Currently participating in other clinical studies or using other investigational drugs.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IL-2 IL-2 The administration period was divided into 6 courses. 6 cycles of IL-2 were administered subcutaneously at a dose of 1 million IU every other day for 2 weeks, followed by a 2-week break in treatment.
- Primary Outcome Measures
Name Time Method ALSFRS-R score week 0，week 24 and week 48 Changes in the rate of ALSFRS-R score during administration period compared with follow-up period
- Secondary Outcome Measures
Name Time Method MRC score week 0，week 24 and week 48 Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period
ALSFRS-R score week 0，week 24 and week 48 Changes in the slope of ALSFRS-R score during adminstration period compared with the follow-up period
ALSAQ-40 score week 0，week 24 and week 48 Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period
NFL in the serum and cerebrospinal fluid week 0，week 24 and week 48 ROADS score week 0，week 24 and week 48 Changes in the rate of ROADS score during adminstration period compared with the follow-up period
Immunological Responses week 0 and week 24 Analysis regulatory CD4+ T (Treg) cells , interleukin 17 (IL-17)-producing helper T (Th17) cells，Teff cells，follicular helper T (Tfh) cells and related cytokines before and during IL-2 treatment.
Trial Locations
- Locations (1)
Peking University Third Hospital
🇨🇳Beijing, Beijing, China