Temporal Interference Stimulation of Hypothalamus in Patients With Narcolepsy Type 1

Official title

Efficacy and Safety of Temporal Interference Stimulation of Hypothalamus in Patients With Narcolepsy Type 1: A Randomised, Double-blind, Sham-Controlled, Single-Centre Trial

Overview

Narcolepsy type 1 (NT1) is a chronic brain disorder caused by selective loss or dysfunction of orexin (hypocretin) neurons in the lateral hypothalamus, for which current pharmacological treatments offer limited efficacy. Temporal interference (TI) stimulation is a recently developed noninvasive neuromodulation technique that enables focal modulation of deep brain structures. In this randomized, double-blind study, we developed a theta-burst patterned TI protocol and evaluated its effects in patients with NT1.

Interventions

• Device Active Temporal Interference Stimulation
  For the active TI stimulation, the current was applied for 40 minutes per session.
• Device Sham Temporal Interference Stimulation
  For the sham stimulation, a brief 30-second current was delivered at the beginning and at the end of each session, with no current applied in between.

Primary outcome measures

• Change from baseline to week 2 in mean sleep latency from the MWT [Time frame: Baseline, Week 2]
• The incidence of adverse events and serious adverse events [Time frame: Baseline, 2-week treatment period, 4-week follow-up period]

Secondary outcome measures (6)

• Change from baseline to week 2 in Epworth Sleepiness Scale total score [Time frame: Baseline, Week 2]
• Change from baseline to week 2 in Narcolepsy Severity Scale score [Time frame: Baseline, Week 2]
• Change from baseline to week 2 in weekly cataplexy frequency [Time frame: Baseline, Week 2]
• Change from baseline to weeks 1, 2, 3, and 4 following treatment in Epworth Sleepiness Scale total score [Time frame: Weeks 1, 2, 3, and 4 following treatment]
• Change from baseline to weeks 1, 2, 3, and 4 following treatment in Narcolepsy Severity Scale score [Time frame: Weeks 1, 2, 3 and 4 following treatment]
• Change from baseline to weeks 1, 2, 3, and 4 following treatment in weekly cataplexy frequency [Time frame: Weeks 1, 2, 3 and 4 following treatment]

Eligibility criteria

Inclusion criteria

• Aged 12 to 60 years.
• Diagnosis of narcolepsy type 1 according to the International Classification of Sleep Disorders, Third Edition (ICSD-3), confirmed by polysomnography (PSG) and/or Multiple Sleep Latency Test (MSLT) performed within the past 10 years, with the test procedures meeting the minimum technical standards specified in the ICSD-3.
• Epworth Sleepiness Scale score >12 at baseline.
• Signed informed consent.

Exclusion criteria

• Presence of other conditions that cause excessive daytime sleepiness, including restless legs syndrome, periodic limb movement disorder, or moderate-to-severe obstructive sleep apnea syndrome, etc.
• History of epilepsy, severe neuropsychiatric disorders, or significant cardiac, hepatic, or renal dysfunction.
• Pregnancy or current breastfeeding.
• Contraindications to MRI or electrical stimulation therapy, such as intracranial metallic foreign bodies, cardiac pacemakers, implantable cardioverter-defibrillators, or cochlear implants.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Xijing Hospital — Xi'an

Publications

• Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. PMID 37857774
• Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024. PMID 28575667
• Xu S, Cui H, Xiao X, Manshaii F, Hong G, Chen J. Precision at Deep Brain: Noninvasive Temporal Interference Stimulation. ACS Nano. 2025 Nov 25;19(46):39589-39614. doi: 10.1021/acsnano.5c15238. Epub 2025 Nov 13. PMID 41232023
• Perez-Carbonell L, Lyons E, Gnoni V, Higgins S, Otaiku AI, Leschziner GD, Drakatos P, d'Ancona G, Kent BD. Adherence to wakefulness promoting medication in patients with narcolepsy. Sleep Med. 2020 Jun;70:50-54. doi: 10.1016/j.sleep.2020.02.013. Epub 2020 Feb 26. PMID 32197224
• Hastings NE, Abdi KE, Bibi F, Aslam B, Nunez MR, Sherani MTR, Shadmani S, Alam U, Hassan VM, Hoor-E-Ainaa, Imran H, Hanna J, Sadat SH. Narcolepsy: Pathophysiology, Diagnosis, Management, and Future Directions, a Narrative Review. Brain Behav. 2025 Dec;15(12):e71116. doi: 10.1002/brb3.71116. PMID 41355371
• Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, Khatami R, Koning F, Kornum BR, Lammers GJ, Liblau RS, Luppi PH, Mayer G, Pollmacher T, Sakurai T, Sallusto F, Scammell TE, Tafti M, Dauvilliers Y. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019 Sep;15(9):519-539. doi: 10.1038/s41582-019-0226-9. Epub 2019 Jul 19. PMID 31324898
• Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000 Sep;27(3):469-74. doi: 10.1016/s0896-6273(00)00058-1. PMID 11055430
• Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000 Sep;6(9):991-7. doi: PMID 10973318

Identifiers

NCT: NCT07727239 · KY20262162-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗