Efficacy and Safety of Adjunctive Minocycline in the Treatment of Autoimmune Encephalitis

Efficacy and Safety of Adjunctive Minocycline in the Treatment of Autoimmune Encephalitis: Open-lable, Randomised, Proof of Concept Study

Autoimmune encephalitis (AE) is an immune-mediated brain disorder characterized by varied clinical manifestations that correlate with specific types of antibodies.Typical symptoms include acute behavioral changes, psychosis, seizures, memory deficits, dyskinesias, speech impairments, and autonomic and respiratory dysregulation.While the majority of patients respond well to immunotherapeutic agents, a significant proportion remains resistant to initial and secondary-line immunotherapies.Minocycline, a semisynthetic tetracycline, is notably used for the central nervous system due to its lipophilic characteristics and its capacity to penetrate the blood-brain barrier. While the primary neuroprotective focus of minocycline in the central nervous system remains unknown, the primary effects of minocycline include the inhibition of microglial activation, mitigation of apoptosis, and reduction in reactive oxygen species generation.Protective effect has been observed in hypoxic injury, ischemic stroke, amyotrophic lateral sclerosis, traumatic spinal cord injury, multiple sclerosis, Parkinson's disease, and Huntington's disease.Can minocycline offer a protective role in AE? Consequently, we proposed a randomized, controlled trial to investigate the efficacy of minocycline in AE.

Study Overview

• Status: Completed
• Conditions: Autoimmune Encephalitis
• Intervention / Treatment: Drug: Minocycline

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Xi'an, China
    • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of definite autoimmune encephalitis(Graus et al 2016.)
2. Age ≥ 18 years
3. Acute or subacute onset (rapid progression of less than 3 months)
4. Reasonable exclusion of alternative causes
5. Written informed consent

Exclusion Criteria:

1. Known allergy to tetracycline antibiotics.
2. Pregnant women.
3. Uncontrolled serious concomitant illness.
4. Known chronic kidney disease stages 3b-5.
5. Moderate liver disease (see Child-Pugh for Classification of Severity of Liver Disease).
6. history of cognitive impairment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Treatment group; Drug: Minocyclin 200 mg oral minocycline for a total of 30 days	Drug: Minocycline; treatment with minocycline combined with first-line drugs for autoimmune encephalitis; Other Names: minocycline hydrochloride
No Intervention: Control group; first-line drugs for autoimmune encephalitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal-Cognitive Assessment (MoCA)scores	the change in MoCA scores from baseline to 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified rankin scale (mRS) scores	The proportion of patients achieving a ≥1-point or ≥2-point improvement in mRS scores at 1 month	1 month
MoCA scores	change in MoCA scores from baseline to months 1, 6, and 12	from baseline to months 1, 6, and 12
mini-mental state examination (MMSE) scores	change in MoCA scores from baseline to months 1, 3, 6, and 12	from baseline to months 1, 3, 6, and 12
Hamilton anxiety scale (HAMA) scores	changes in HAMA scores from baseline to months 1, 3, 6, and 12	from baseline to months 1, 3, 6, and 12
Hamilton depression scale (HAMD) scores	changes in HAMA scores from baseline to months 1, 3, 6, and 12	from baseline to months 1, 3, 6, and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebrospinal fluid (CSF) levels of Soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2)	the change in CSF levels of sTREM2 levels from baseline to months 1, 3, 6, and 12.	from baseline to months 1, 3, 6, and 12.

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Actual): June 3, 2024
• Study Completion (Actual): July 16, 2025

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: minocycline; autoimmune encephalitis
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Autoimmune Diseases of the Nervous System; Hashimoto Disease; Anti-Bacterial Agents; Anti-Infective Agents; Minocycline
• Other Study ID Numbers: XJLL-KY-20232121

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