Study on the Clinical Efficacy of Transcranial Strong Alternating Current (Hi-tACS) in Patients With Neuroimmune Diseases With Insomnia

This study aims to comprehensively evaluate the therapeutic effects of high-intensity transcranial alternating current stimulation (hi-tACS) on insomnia symptoms in patients with idiopathic inflammatory demyelinating disorders (IIDDs) by analyzing both the overall disease characteristics of IIDDs and individual patient variability. Additionally, the study will investigate the neuroimmunomodulatory mechanisms of hi-tACS. The findings are expected to provide evidence for the clinical application of hi-tACS in managing insomnia in IIDDs and offer new insights for personalized treatment strategies.

Study Overview

• Status: Recruiting
• Conditions: Neuroimmune Diseases With Insomnia
• Intervention / Treatment: Device: high-intensity transcranial alternating current stimulation, hi-tACS; Device: Sham hi-tACS

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

Contacts and Locations

• Study Contact: Name: Yinan Zhao; Phone Number: +86 135 0405 1368; Email: zyn1616@xwhosp.org

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Beijing, China
      • Contact: Yinan Zhao; Phone Number: +86 135 0405 1368; Email: zyn1616@xwhosp.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with idiopathic inflammatory demyelinating disorders (IIDDs) meeting the diagnostic criteria, including neuromyelitis optica spectrum disorders (NMOSD) [based on the Chinese Guidelines for Diagnosis and Treatment of Neuromyelitis Optica Spectrum Disorders (2016 Edition)] and multiple sclerosis (MS) [based on the Chinese Guidelines for Diagnosis and Treatment of Multiple Sclerosis (2023 Edition)], and accompanied by insomnia.

   • Aged between 18 and 65 years, regardless of gender.
   • Experiencing difficulty falling asleep, difficulty maintaining sleep, or early morning awakening on at least 3 nights per week for more than 3 months.
   • Severe daytime functional impairment (Chinese version of the Pittsburgh Sleep Quality Index, item 7 [daytime dysfunction] ≥2).
   • Having not taken hypnotics or insomnia treatment medication for at least 4 months.
   • Female participants aged 18-50 years who agree to use effective contraception throughout the study period.
   • Agreeing to refrain from receiving medication or other non-pharmacological treatments during the study period.
   • Agree to participate and sign the informed consent.

2. Patients diagnosed with chronic primary insomnia according to 《The Diagnostic and Statistical Manual of Mental Disorders》(Text Revision) (DSM-IV-TR) or 《International Classification of Diseases Tenth Revision》(ICD-10):

   • Aged between 18 and 65 years, regardless of gender.
   • Experiencing difficulty falling asleep, difficulty maintaining sleep, or early morning awakening on at least 3 nights per week for more than 3 months.
   • Severe daytime functional impairment (Chinese version of the Pittsburgh Sleep Quality Index, item 7 [daytime dysfunction] ≥2).
   • Having not taken hypnotics or insomnia treatment medication for at least 4 months.
   • Female aged 18~50 years agreeing to adopt birth control measures during the study period.
   • Agreeing to refrain from receiving medication or other non-pharmacological treatments during the study period.
   • Agree to participate and sign the informed consent.

Exclusion Criteria:

• History of relapse within the past 1 month.
• Drug adjustment within the past 1 month, or receipt of modified electroconvulsive therapy, transcranial magnetic stimulation therapy, or other neuralcontroltechnology therapy.
• Participation in any other clinical studies within 1 month prior to enrollment or currently.
• Presence of cochlear implant system, cardiac-pacemaker, or intracerebral implanted stimulators.
• Impaired skin integrity at the electrode placement site, or allergy to electrode gel or adhesive.
• History of organic brain diseases such as epilepsy, hydrocephalus, tumor of central nervous system, craniocerebral injury, or intracranial infection.
• Pregnant or lactating women, or those intending pregnancy soon;
• A score of ≥3 on the suicide item of the Hamilton Depression Scale, or coexisting severe mental disorders;
• Presence of severe or unstable organic diseases;
• Work night shifts;
• Presence of other sleep disorders;
• Poor patient compliance preventing cooperation with treatment, follow-up, or clinical, electroencephalographic (EEG), or imaging data collection;
• Other circumstances deemed by the investigator as inappropriate for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neuromodulation Group; Participants receive active transcranial alternating current stimulation (tACS) using the Nexalin ADI device. Electrodes are placed on the forehead (Fp1, Fpz, Fp2 areas of the international 10-20 system; electrode size 4.45 cm × 9.53 cm) and on bilateral mastoids (two electrodes, each 3.18 cm × 3.81 cm). Each session lasts 40 minutes, once daily, for 4 consecutive weeks (5 days intervention + 2 days rest, total 20 sessions). After completing the 20 sessions, there is a 4-week follow-up period without any treatment. At the end of week 4 and at 1 month and 2 months post-treatment, participants are asked about discomfort, abnormal sensations, seizure occurrence, and treatment acceptability.	Device: high-intensity transcranial alternating current stimulation, hi-tACS; Operations are performed by trained and qualified researchers using the Nexalin ADI device. For both real and sham treatments, 1 electrode (4.45 cm × 9.53 cm) is placed on the prefrontal lobe (corresponding to the Fp1, Fpz, and Fp2 regions of the International 10-20 system scalp EEG recording electrodes), and 2 electrodes (3.18 cm × 3.81 cm each) are placed on the bilateral mastoids (one on each side). Each participant receives 20 sessions of tACS intervention under the same guiding instructions, once daily for 40 minutes, for 4 consecutive weeks (5 intervention days + 2 rest days per week). After completing 20 consecutive treatments, participants enter a 4-week observation follow-up period without any treatment.
Placebo Comparator: Sham Neuromodulation Group; Participants receive sham stimulation using a device identical in appearance, buttons, electrodes, odor, and weight to the active device, but no current is delivered. Both participants and investigators are blinded to group assignment. The sham device produces an initial similar sensation to real stimulation to maintain blinding. The treatment schedule (once daily, 40 minutes per session, 20 sessions over 4 weeks) and follow-up assessments are identical to those in the active group.	Device: Sham hi-tACS; The sham treatment device is identical to the real device in all aspects (appearance, buttons, electrodes, odor, weight, etc.) except that it does not emit electrical current. Neither participants nor researchers can distinguish between the real and sham devices by appearance. This design creates an initial sensory experience similar to actual stimulation while maintaining the double-blind nature of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in Pittsburgh Sleep Quality Index (PSQI) scores	Change in Pittsburgh Sleep Quality Index (PSQI) scores from baseline to 2 months post-treatment.	From baseline to 2 months after completion of the 4-week treatment period (up to approximately 12 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in PSQI scores	Changes in PSQI scores at baseline, at the end of the 4-week treatment, and 1 month after treatment	From baseline to 1 month after completion of the 4-week treatment period (i.e., up to approximately 8 weeks), with assessments conducted at baseline, at the end of the 4-week treatment (after 20 treatment sessions), and 1 month post-treatment.
The changes in Insomnia Severity Index (ISI) scores	Changes in Insomnia Severity Index (ISI) scores at the end of the 4-week treatment, and at 1 and 2 months after treatment.	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
The changes in Hamilton Depression Scale (HAMD) scores	Changes in Hamilton Depression Scale (HAMD) scores at the end of the 4-week treatment, and at 1 and 2 months after treatment.	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
The changes in ini-MentalState Examination scores (MMSE) scores	Changes in Mini-Mental State Examination (MMSE) scores at the end of the 4-week treatment and at 1 and 2 months after treatment.	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
The changes in Fatigue Severity Scale (FSS) scores	Changes in Fatigue Severity Scale (FSS) scores at the end of the 4-week treatment and at 1 and 2 months post-treatment	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
The changes in Epworth Sleeping Scale (ESS) scores	Changes in Epworth Sleeping Scale (ESS) scores at the end of the 4-week treatment and at 1 and 2 months after treatment.	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
The changes in ShortForm-36 Health Survey (SF-36) scores	Changes in ShortForm-36 Health Survey (SF-36) scores at the end of the 4-week treatment and at 1 and 2 months post-treatment.	From the end of the 4-week treatment period (after 20 treatment sessions) to 2 months post-treatment (up to approximately 12 weeks from baseline), with assessments conducted at the end of treatment, and at 1 and 2 months after treatment.
Changes in accuracy rates and reaction times of emotional face recognition tasks, along with variations in power spectrum, entropy, and coherence metrics	Changes in accuracy and reaction time in the emotional face recognition task, as well as in power spectrum, entropy, and coherence metrics, from baseline to post-treatment and follow-up assessments.	From baseline to 2 months after completion of the 20-session treatment period (up to approximately 12 weeks), with assessments conducted at baseline, immediately before and after the 20 treatment sessions, and at 1- and 2-month post-treatment follow-ups.
The changes in lymphatic tissues	Radiological evaluation of lymphatic tissues includes: observation of changes in lymph nodes, lymphoid tissues, and drainage vessels at the end of the 4-week treatment, and at 1 and 2 months after treatment.	From baseline to 2 months after completion of the 4-week treatment period (up to approximately 12 weeks), with assessments conducted at the end of treatment (after 20 treatment sessions), and at 1 and 2 months post-treatment
Alterations in Brain Networks	Alterations in Brain Networks: Monitoring via MRI and Polysomnography (PSG) at the end of the 4-week treatment(at the end of 20 treatment sessions), and at 1 and 2 months after treatment	From baseline to 2 months after completion of the 4-week treatment period (up to approximately 12 weeks), with assessments conducted at baseline, at the end of treatment (after 20 treatment sessions), and at 1 and 2 months post-treatment
The changes in laboratory biomarkers	Changes in laboratory biomarkers, including IL-6, TNF-α, and IL-1β, were assessed at baseline, at the end of the 4-week treatment (i.e., after completion of 20 treatment sessions), and at 1- and 2-month post-treatment follow-ups.	From baseline to 2 months after completion of the 4-week treatment period (up to approximately 12 weeks), with assessments conducted at the end of treatment (after 20 treatment sessions), and at 1 and 2 months post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Effects Assessment Scale for Transcranial Alternating Current Stimulation (tACS-AE Scale)	Adverse Effects Assessment Scale for Transcranial Alternating Current Stimulation (tACS-AE Scale)	From the first treatment session to the end of the 4-week treatment period (20 sessions; up to approximately 4 weeks), with assessments conducted at each treatment session

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Junwei Hao, Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Beijing, China

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: [2025]043-002; MR-11-25-042133 (Registry Identifier: Study on the clinical efficacy of transcranial strong alternating current (hi-tACS) in patients with neuroimmune diseas)

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