Non-invasive Neurostimulation as a Tool for Diagnostics and Management for Neurodegenerative Diseases

Double blinded, sham-controlled, randomized trial on repeated transcranial alternating current brain stimulation (tACS) in neurodegenerative diseases. The investigators will evaluate whether a 4-times daily repeated stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with neurodegenerative diseases, including dementia with Lewy Bodies, Alzheimer's disease, idiopathic normal pressure hydrocephalus and Frontotemporal dementia.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Frontotemporal Dementia; Dementia With Lewy Bodies
• Intervention / Treatment: Device: Gamma tACS (40 Hz) over the superior parietal cortex

Detailed Description

Double blinded, sham-controlled, randomized trial on repeated transcranial alternating current brain stimulation (tACS) in neurodegenerative diseases. The investigators will evaluate whether a 4-times daily repeated stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with neurodegenerative diseases, including dementia with Lewy Bodies, Alzheimer's disease, idiopathic normal pressure hydrocephalus and Frontotemporal dementia.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eino Solje, MD, PhD; Phone Number: +358 17 713 311; Email: eino.solje@uef.fi

Study Locations

• Finland
  • Kuopio, Finland
    • Recruiting
    • Kuopio University Hospital
    • Contact: Eino Solje

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mild Cognitive Impairment due to Alzheimer's disease
• Dementia with Lewy Bodies
• Frontotemporal dementia
• Idiopathic normal pressure hydrocephalus (iNPH)

Exclusion Criteria:

• History of seizures
• Pregnancy
• Metal implants in the head (except dental fillings)
• Electronic implants (i.e. pace-maker, implanted medical pump)
• Age <18 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real tACS; Four sessions (once a day, during four consecutive days) of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus)	Device: Gamma tACS (40 Hz) over the superior parietal cortex; Single session of gamma tACS (40 Hz) over the superior parietal cortex
Placebo Comparator: Sham tACS; Four sessions of sham tACS (once a day, during four consecutive days) over the superior parietal cortex (Precuneus)	Device: Gamma tACS (40 Hz) over the superior parietal cortex; Single session of gamma tACS (40 Hz) over the superior parietal cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Rey Auditory Verbal Learning Test score	Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The examiner reads aloud 15 unrelated words and the participant is asked to recall the words after each of the five trials. After a 15 minute delay, the participant is asked again to recall the words. The score ranges from 0 (worst performance) to 75 (best performance).	Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention
Changes in Rey Auditory Verbal Learning Test, recognition	Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. After a 15 minute delay, the participant is asked to recognise the original 15 words intermixed with 31 distractor words. The score of the recognition part ranges from 0 (worst performance) to 46 (best performance).	Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention
Changes in orientation to time and place (MMSE questions 1-10)	10 questions about the orientation. The score ranges from 0 (worse performance) to 10 (best performance).	Baseline (immediately before the intervention), immediately after the last intervention, 4 weeks after the last intervention
Changes in Trail Making A & B tests	TMT A & B tests. Time to perform set is recorded.	Baseline (immediately before the intervention), immediately after the 4th intervention, 4 weeks after the last intervention
Changes in INECO Frontal Screening test	Test battery assessing frontal lobe functions. The score ranges from 0 (worse performance) to 30 (best performance)	Baseline (immediately before the intervention), immediately after the 4th intervention, 4 weeks after the last intervention
Changes in phonemic fluency	Person is requested to provide as many words as possible starting with certain letter. The score is the sum of all acceptable words produced in one minute.	Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SAI measurements	By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic neurotransmission.	Baseline (immediately before the intervention), immediately after the last intervention
Change in SICI measurements	By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short interval intracortical inhibition (SICI), which is a marker of gabaergic neurotransmission.	Baseline (immediately before the intervention), immediately after the last intervention
Change in ICF measurements	By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on intracortical facilitation (ICF), which is a marker of glutamatergic neurotransmission.	Baseline (immediately before the intervention), immediately after the last intervention

Collaborators and Investigators

• Sponsor: Kuopio University Hospital
• Investigators: Principal Investigator: Eino Solje, MD, PhD, Kuopio University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): July 1, 2032

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; TDP-43 Proteinopathies; Proteostasis Deficiencies; Tauopathies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Alzheimer Disease; Neurodegenerative Diseases; Lewy Body Disease; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: KUH5772859

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pseudonymized data upon request, according to Finnish national and EU GDPR regulations
• IPD Sharing Time Frame: Data will be shared after the study completion indefinitely.
• IPD Sharing Access Criteria: Reasonable request

Drug and device information, study documents

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