IL-2 in Refractory Autoimmune Encephalitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.

Detailed Description
-----------------
Autoimmune encephalitis is a recently recognized etiology of encephalitis which is mediated by various autoantibodies targeting neural cells or synapses. The responses to immunotherapy is generally good, considerable proportion of patients with autoimmune encephalitis have unfavorable clinical outcomes. Recently, depletion of regulatory T cell (Treg cell) is reported in variable autoimmune diseases and multiple studies have shown that low-dose interleukin-2(IL-2) specifically activates Treg cells to control autoimmunity and inflammation. Protocol: This study is a single arm open-label study assessing clinical responses to the administration of low-dose IL-2 in autoimmune encephalitis patients who are refractory to first- and second-line immunotherapy. Objective: To assess the efficacy of low-dose IL-2 in autoimmune encephalitis, resistant to first- and second- line immunotherapy. Methods: This is a single arm open-label study. Each patients will receive four cycles of subcutaneous Proleukin (Interleukin-2, IL-2) (Week-1; 1.5 million IU (MIU)/d from Day-1 to Day-5, Week-3, -6, -9; 3MIU/d from Day-1 to Day-5) in the hospital. The patients will be followed up for 3 months (Week-21). Primary outcome - clinical efficacy by modified Rankin Scale Secondary outcome - Immunologic follow-up of Treg cells before, during, and after IL-2 therapy, quality of life, cognitive function, side effect of low-dose IL-2

Official Title
-----------------
Effect of IL-2 in Refractory Autoimmune Encephalitis Patients: A Pilot Study

Conditions
-----------------
Encephalitis

Intervention / Treatment
-----------------
* Drug: Proleukin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Clinical diagnosis of autoimmune encephalitis Positive for autoantibody (serum and or CSF) : NMDAR, anti-leucine-rich glioma inactivated-1(LGI-1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) 1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/collapsing response mediator protein 5 (CRMP5), -amphiphysin, or glutamic acid decarboxylase (GAD) Refractory to first-line (high-dose steroid or intravenous immunoglobulin) and second line (rituximab or cyclophosphamide) immunotherapy Written informed consent form. Exclusion Criteria: low hemoglobin <8.0 g/dL, absolute neutrophil count<1600/mm3, lymphocytes <600/mm3, platelets <140,000/mm3 heart failure (≥ grade III NYHA), hepatic insufficiency (aspartate amino transferase >200 IU/L, amino alanine transferase, >200 IU/L), or lung failure Positive for HIV serology, active hepatitis B Significant abnormality in chest X-ray other than these linked to the diseases under investigation Infection Other progressive neurological degenerative disease. Poor venous access not allowing repeated blood tests pregnant or lactating women

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proleukin<br>Proleukin (subcutaneous injection) 1.5 MIU/day from day 1 to 5 at W1 3 MIU/day from day 1 to day 5 at W3, W6, and W9 | Drug: Proleukin<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of modified Rankin scale |  | Week 0,12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of percentage of regulatory T (Treg) cells |  | Week 1, 3, 5, 9, 12, 21 | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | Week 1, 3, 5, 9, 12, 21 | 
| Quality of Life in Epilepsy Inventory (QOLIE)-31 | Quality of Life in Epilepsy Inventory (QOLIE)-31 | Week 21 | 
| Beck Depression Inventory (BDI) | Beck Depression Inventory (BDI) | Week 21 | 
| Cognitive function | Mini-mental state examination (MMSE) | Week 21 |