PE: Immunotherapy in Autoimmune Encephalitis

Sponsor

Yan Zhang (Other)

Overall Status

Recruiting

CT.gov ID

NCT03542279

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Encephalitis	Procedure: Plasma exchange Drug: IVIG, High-dose glucocorticoid	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective Randomized Controlled Trial of Plasma Exchange in Autoimmune Encephalitis

Actual Study Start Date :

Jan 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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.

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

Drug: IVIG, High-dose glucocorticoid

Outcome Measures

Primary Outcome Measures

modified Rankin Scale [after 3 months following Immunotherapy]
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.

Secondary Outcome Measures

modified Rankin Scale [after 1 year following Immunotherapy]
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.
modified Rankin Scale [after 2 years following Immunotherapy]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

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.
1. Previous history of IVIG allergy.
1. Severe nerve dysfunction (mRS>3) before the onset.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xuanwu Hospital of Capital Medical University	Beijing	Beijing	China	100053

Sponsors and Collaborators

Yan Zhang

Investigators

Study Chair: Yan Zhang, Phd, Xuanwu Hospital, Beijing

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yan Zhang, Principal Investigator, Xuanwu Hospital, Beijing

ClinicalTrials.gov Identifier:

NCT03542279

Other Study ID Numbers:

AE-PE

First Posted:

May 31, 2018

Last Update Posted:

Mar 3, 2020

Last Verified:

Mar 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Yan Zhang, Principal Investigator, Xuanwu Hospital, Beijing

Autoimmune encephalitis, Plasma exchange, Immunotherapy, Outcome

Additional relevant MeSH terms:

Encephalitis

Hashimoto Disease

Glucocorticoids

Study Results

No Results Posted as of Mar 3, 2020