Clinical trial NCT06385106: Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Alzheimer's Disease
Official title: Effects of Repetitive Transcranial Magnetic Stimulation on Sleep and Cognitive Function in Patients With Alzheimer's Disease: a Randomized, Double-blind, Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
sleep
Glymphatic System
Transcranial Magnetic Stimulation
cognitive impairment
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2024-04-25
Enrollment: 30
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive function in Alzheimer's disease (AD), but studies on the improvement of sleep disorders in AD are limited. The aim of this study was to evaluate the effects of rTMS on sleep and cognition in patients with mild-to-moderate Alzheimer's disease (AD).

Detailed description: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Some studies have showed that its positive effects in patients with Alzheimer's disease. The aim of this study was to evaluate the effect of rTMS on sleep and cognitive function in patients with mild to moderate AD, and to evaluate the glymphatic system function's mediating role between sleep and cognitive function. The study involves participants receiving 10 sessions of high frequency rTMS treatment applied to the dorsolateral prefrontal cortex over a 5 days period or sham rTMS. Neuropsychological testing and polysomnography will be used as the primary outcome measures. In addition, magnetic resonance imaging will be used to explore the effect of rTMS on the glymphatic system function in patients with Alzheimer's disease. Follow-up assessments of the patients' status will be conducted at one and three-month intervals.

Eligibility criteria: Inclusion Criteria:

1. Participant meets 2014 IWG-2 criteria for hippocampal amnestic syndrome, typical of AD, with progressive episodic memory impairment confirmed by neuropsychology. Cerebrospinal fluid markers (Aβ40, Aβ42, T-tau, p-tau) consistent with AD, or AV-45 PET imaging showing significant cortical tracer retention, in line with AD pathophysiology.
2. Age range: 55-80 years.
3. No visual or hearing impairment.
4. Right-handed.
5. Han nationality.
6. Signed informed consent.
7. Reliable caregivers as information providers.
8. MMSE score: 10-27; CDR: 0.5-2 points.
9. If receiving approved AD treatment (e.g., acetylcholinesterase inhibitor or memantine), dose must be stable for ≥3 months prior to screening and unchanged unless medically necessary.

Exclusion Criteria:

1. History of seizures or epilepsy diagnosis;
2. Stroke history;
3. Nervous system diseases causing brain dysfunction (schizophrenia, severe anxiety/depression, dementia, Huntington's, brain tumors, Parkinson's, metabolic encephalopathy, encephalitis, MS, epilepsy, brain trauma, hydrocephalus);
4. Severe liver/kidney/lung dysfunction, anemia, gastrointestinal disease, arrhythmia, recent MI;
5. Barbiturate/benzodiazepine use within 2 weeks;
6. MRI/TMS contraindications (metallic implants);
7. Systemic diseases causing cognitive impairment (hypothyroidism, folate/B12 deficiency, infections, alcohol/drug abuse);
8. Aphasia, consciousness disturbance, inability to cooperate;
9. TMS/tDCS/DBS has been processed;
10. Underlying pathology other than AD;
11. Focal brain lesions on T1/T2 images;
12. Refusal to sign informed consent.

Primary outcomes:
measure: Cognitive funtion
timeFrame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later
measure: Sleep parameters
timeFrame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later
Secondary outcomes:
measure: glymphatic system
timeFrame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Benyan Luo, PhD
role: STUDY_CHAIR
References:
citation: You S, Lv T, Qin R, Hu Z, Ke Z, Yao W, Zhao H, Bai F. Neuro-Navigated rTMS Improves Sleep and Cognitive Impairment via Regulating Sleep-Related Networks' Spontaneous Activity in AD Spectrum Patients. Clin Interv Aging. 2023 Aug 15;18:1333-1349. doi: 10.2147/CIA.S416992. eCollection 2023.
citation: Siow TY, Toh CH, Hsu JL, Liu GH, Lee SH, Chen NH, Fu CJ, Castillo M, Fang JT. Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults. Neurology. 2022 Feb 22;98(8):e829-e838. doi: 10.1212/WNL.0000000000013215. Epub 2021 Dec 14.
citation: Herring WJ, Ceesay P, Snyder E, Bliwise D, Budd K, Hutzelmann J, Stevens J, Lines C, Michelson D. Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimers Dement. 2020 Mar;16(3):541-551. doi: 10.1002/alz.12035. Epub 2020 Jan 15.