Immunotherapy in Autoimmune Encephalitis (PE)

Prospective Randomized Controlled Trial of Plasma Exchange in Autoimmune Encephalitis

The study is to explore the treatment effects and long-term prognosis (12 months and 24 months after immunotherapy) by comparing the early plasma exchange (PE) combined with medication therapy with the PE after medication immunotherapy in autoimmune encephalitis (AE) patients, to make clear that the early PE can be more effective than the treatment of PE after medication immunotherapy. As well as, the study is to explore whether PE is also effective in AE with autoantibody synthesis in the sheath, positive cerebrospinal fluid antibody and seronegative.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Encephalitis
• Intervention / Treatment: Procedure: Plasma exchange; Drug: IVIG, High-dose glucocorticoid

Detailed Description

Patients with AE will be randomly divided into the early PE group and the non-early PE group according to the random table. All patients will receive tumour screening, symptomatic supportive treatment, and immunotherapy. The immunotherapy includes high-dose corticosteroid, intravenous gamma immunoglobulin (IVIG; 0.4 g/kg/d for each course for 5 d), PE and immunosuppressants. The immunosuppressants will be given after enrolled 4 weeks. High-dose corticosteroid and PE will be given before IVIG in the early PE group. PE will be given after high-dose corticosteroid and IVIG 2 weeks in the non-early PE group. The mRS will be used for outcome evaluations. The outcomes will be evaluated after 2, 3, 6, 12, and 24 months respectively following immunotherapy. The evaluation standards were as follows: a mRS of 0-2 points is a favourable outcome, and 3-6 points is an unfavourable outcome. Statistically analyses will be employed to examine the differences in outcomes between the severe and non-severe groups.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Zhang, Phd; Phone Number: 8613671376710; Email: zhangylq@sina.com
• Study Contact Backup: Name: Wei-bi Chen, Phd; Phone Number: 8424 86-010-83198899; Email: chenweibi@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital of Capital Medical University
      • Contact: Lin-lin Fan, Phd; Phone Number: 8424 86-010-83198899; Email: windspring7139@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis can be made when all four* of the following criteria have been met:

  1. Subacute onset (rapid progression of less than 3 months) of working memory deficits,seizures, or psychiatric symptoms suggesting involvement of the limbic system
  2. Bilateral brain abnormalities on T2-weighted fl uid-attenuated inversion recovery MRI highly restricted to the medial temporal lobes†

  3. At least one of the following:

     • CSF pleocytosis (white blood cell count of more than fi ve cells per mm3)
     • EEG with epileptic or slow-wave activity involving the temporal lobes
  4. Reasonable exclusion of alternative causes

Exclusion Criteria:

• 1. Serious underlying diseases, such as severe active hemorrhage, disseminated intravascular coagulation, severe hypotension or shock, unstable cardiac failure, cerebral hernia, severe infection, severe abnormal mental behaviors and other endangered conditions.
• 2. Previous history of IVIG allergy.
• 3. Severe nerve dysfunction (mRS>3) before the onset.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early PE group; PE (3-5 times in each course) combined with high-dose glucocorticoid, and IVIG after PE.	Procedure: Plasma exchange; PE treatments are performed on an apheresis device (Fresenius MultiFiltrate hemodialysis filtration machine, German). PE volumes of 1 plasma volume per procedure will be used. Treatments will be given every other day with breaks allowed for weekends for most patients. The anticoagulant used is low molecular heparin. The use of high-dose glucocorticoid is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.; Drug: IVIG, High-dose glucocorticoid; IVIG is given 0.4 g/kg/d for each course for 5 days. The use of high-dose glucocorticoid is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.
Active Comparator: Non-early PE group; IVIG (0.4 g/kg/d for each course for 5 d) combined with high-dose glucocorticoid, and PE after IVIG 2 weeks.	Procedure: Plasma exchange; PE treatments are performed on an apheresis device (Fresenius MultiFiltrate hemodialysis filtration machine, German). PE volumes of 1 plasma volume per procedure will be used. Treatments will be given every other day with breaks allowed for weekends for most patients. The anticoagulant used is low molecular heparin. The use of high-dose glucocorticoid is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.; Drug: IVIG, High-dose glucocorticoid; IVIG is given 0.4 g/kg/d for each course for 5 days. The use of high-dose glucocorticoid is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. A score of 0-2 was considered a favorable outcome, whereas a score of 3-6 was graded as an unfavorable one.	after 3 months following Immunotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. A score of 0-2 was considered a favorable outcome, whereas a score of 3-6 was graded as an unfavorable one.	after 1 year following Immunotherapy
modified Rankin Scale	modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. A score of 0-2 was considered a favorable outcome, whereas a score of 3-6 was graded as an unfavorable one.	after 2 years following Immunotherapy

Collaborators and Investigators

• Sponsor: Yan Zhang
• Investigators: Study Chair: Yan Zhang, Phd, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): May 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 3, 2020
• Last Update Submitted That Met QC Criteria: March 1, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Autoimmune encephalitis, Plasma exchange, Immunotherapy, Outcome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Hashimoto Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: AE-PE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No