Effects of Esketamine on Consciousness-related Brain Network Characteristics in Patients With Prolonged Disorders of Consciousness

Prolonged disorders of consciousness (pDoC) are pathologies in which there is a loss of consciousness for more than 28 days. The number of patients with pDoC is increasing as the level of critical care treatment and monitoring improves. However, clinical trials for patients with pDoC are limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use. In recent years, ketamine has been used with remarkable success in the treatment of neuropsychiatric disorders by inducing neuroplasticity, increasing neurophysiologic complexity, and expanding functional brain connectivity states. Considering increased brain plasticity as well as brain complexity, it may be beneficial for consciousness recovery. In this study, the investigators aimed to explore the effects of esketamine on brain networks and level of consciousness in patients with pDoC, and to discuss its possible use as a wakefulness-promoting treatment for patients with pDoC.

Study Overview

• Status: Recruiting
• Conditions: Prolonged Disorders of Consciousness
• Intervention / Treatment: Drug: Drug: Esketamine (Continuous infusion)

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100070
    • Recruiting
    • Beijing Tiantan Hospital, Capital Medical University
    • Contact: Ruquan Han, M.D., Ph.D; Phone Number: 8610-59976660; Email: ruquan.han@gmail.com
    • Principal Investigator: Ruquan Han, M.D., Ph.D

Participation Criteria

Eligibility Criteria

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

Description

Patients with prolonged disorders of consciousness:

Inclusion Criteria:

• Age 18 - 65 years old, native Chinese speaker, dextromanual;
• Chronic disorder of consciousness;
• Spinal cord electrical stimulator implantation under general anesthesia;
• Signed informed consent.

Exclusion Criteria:

• Continuous sedation was administered within 72 hours prior to the study;
• Open head injury, parenchymal resection and other damage of brain structural integrity;
• The intracranial compliance decreased due to hydrocephalus and swelling;
• Known hearing impairment;
• Airway stenosis and various causes of severe ventilation or ventilation dysfunction;
• Known or suspected severe cardiac, pulmonary, hepatic, and renal dysfunction;
• History of drug allergy to esketamine;
• Associated with other mental or neurological diseases;
• Other reasons are not suitable to participate in this study.

Healthy brain volunteers:

Inclusion Criteria:

• Age 18 - 65 years old;
• Patients undergoing surgical treatment under elective general anaesthesia;
• American Society of Anesthesiologists (ASA) I-II;
• Native Chinese speaker;
• Dextromanual;
• Signed informed consent.

Exclusion Criteria:

• Previous history of craniocerebral disease, imaging suggests organic brain lesions;
• People with uncontrolled hypertension, hyperthyroidism, elevated intracranial pressure, epileptic seizures;
• History of drug allergy to esketamine;
• Hearing abnormality;
• History of drug and alcohol abuse;
• People with mental and behavioral disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy brain volunteers	Drug: Drug: Esketamine (Continuous infusion); Continuous intravenous infusion of ketamine at a dose of 0.3mg/(kg · h). Collect resting state EEG and auditory event-related potential (ERP) before administration (baseline), 60 minutes after administration, 30 and 60 minutes after discontinuation.
Experimental: Patients with prolonged disorders of consciousness	Drug: Drug: Esketamine (Continuous infusion); Continuous intravenous infusion of ketamine at a dose of 0.3mg/(kg · h). Collect resting state EEG and auditory event-related potential (ERP) before administration (baseline), 60 minutes after administration, 30 and 60 minutes after discontinuation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Entropy index.	A higher entropy index indicates a higher brain complexity.	During the trial(up to 3 hours for each subject).
Lempel Ziv complexity.	Higher Lempel Ziv complexity indicates higher brain complexity.	During the trial(up to 3 hours for each subject).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG Spectral Characteristics	EEG power spectrum characteristics of pDoC patients under esketamine. administration, including the δ, θ, α, β, and γ frequency bands.	During the trial(up to 3 hours for each subject).
Cortical Connectivity	Characteristics of the weighted phase lag index(WPLI) in patients with pDoC. 0 ≤ WPLI ≤ 1, where 0 represents asynchronous and 1 represents synchronous.	During the trial(up to 3 hours for each subject.
Rate of patients recovered consciousness after surgery	Rate of patients recovered consciousness 30 days, 90 days, 180 days after surgery.	During the trial(through study completion, 180 days).

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: June 23, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 23, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Esketamine; Event-related potential; Multichannel electroencephalogram; Brain network characteristics
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: LY20240424

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No