Clinical Trial Through Combined tACS Therapy in Patients With Mild Cognitive Impairment

NCT05291208 | Unknown Phase 2 DMC

• 1 other identifier: SA19I0118
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The aging of the population has led to an increase in the prevalence of disabling and high-cost diseases, such as dementia and Mild Cognitive Impairment (MCI). The latter can be considered a prodromal phase of some dementias and a critical stage for interventions to postpone the impairment of functionality and thus maintain a better quality of life. A cognitive function to intervene in working memory (WM) since it represents the fundamental component of executive functions and is the gateway to maintaining long-term memory. This project proposes an intervention to enhance WM in these users, combining cognitive training with non-invasive brain stimulation, specifically transcranial electrical stimulation of alternating current (tACS). This proposal arises from recent evidence showing that it is possible to increase the capacity of WM in users with MCI through cognitive training. Along with this, tACS has been proposed as a specific neuronal plasticity inducer for the oscillatory pattern required for each mental process. WM is a process particularly susceptible to being enhanced by this technique, as the underlying electrophysiological oscillatory patterns of this process are well described. Thus, tACS would act as a potentiator of the residual capacity of WM in patients with neurodegenerative diseases. This study is a phase II randomized, double-blind clinical trial with a 3-month follow-up. The study will be of 62 participants diagnosed with MCI over 60 years from Valparaíso, Chile. Participants will receive intervention that will combine 12 cognitive training sessions with non-invasive brain stimulation, specifically tACS. Depending on the intervention group to which they will be assigned, in 8 of these sessions, participants will receive either tACS or sham stimulation. Sessions will last approximately 1 hour and take place twice a week, over six weeks. The primary outcomes will be the electroencephalographic measurements, and the secondary effects will be cognitive assessments of WM. The outcomes will be performed before, immediately after, and three months after the end of the intervention. The outcomes of this trial will add evidence about the benefits and feasibility of an intervention that combines cognitive training with non-invasive brain stimulation. The objective is to contribute tools for optimal cognitive treatment in patients with MCI. To enhance WM capacity, postpone the impairment of functionality, and obtain a better quality of life.

Conditions

Mild Cognitive Impairment

Keywords

cognitive training; cognitive functions; non-invasive brain stimulation.; working memory

Outcome Measures

Primary Outcomes (1)

• Prefrontal theta oscillation activity.

  The ratio of change of the normalized power (mean/standard error, micro Volt2 ) of prefrontal theta oscillation (5-10 Hz, Fz electrode) related to Successful Memory Performance. The prefrontal theta oscillation related to Successful Memory Performance (SMP) is calculated based on a single-trial general linear model that include SMP as the regressor of interest and Memory Load as a secondary regressor.

  week 1 (pre-intervention), week 8 (1 week post intervention), week 20 (12 weeks post intervention)

Secondary Outcomes (3)

• WAIS-IV Digit Retention subtest. Chilean standard. (Rosas et al., 2015)

  week 1 (pre-intervention), week 8 (1 week post intervention), week 20 (12 weeks post intervention)

• Trail Making Test B (TMT-B). Chilean standard. (Arango-Lasprilla et al., 2015)

  week 1 (pre-intervention), week 8 (1 week post intervention), week 20 (12 weeks post intervention)

• Parietal theta oscillation activity.

  week 1 (pre-intervention), week 8 (1 week post intervention), week 20 (12 weeks post intervention)

Study Arms (2)

Treatment group

EXPERIMENTAL

This group will receive a cognitive training intervention combined with alternating current electrical stimulation (i.e., treatment).

Combination Product: Combined tACS and Cognitive Training Program

Control group

SHAM COMPARATOR

This group will receive a traditional cognitive training intervention with sham electrical stimulation.

Behavioral: Traditional Cognitive Training Program

Interventions

Combined tACS and Cognitive Training Program COMBINATION_PRODUCT

The program contemplates 12 WM training sessions based on tasks of storage and manipulation of verbal and visuospatial information, with a frequency of twice a week during six weeks (total of 12 sessions). Patients will receive real electrical stimulation for 10 minutes during verbal working memory task. This includes 10s periods of phase-in and 10 s of phase-out and will be done in parallel with the cognitive intervention program in sessions 3, 4, 5, 6, 7, 8, 9, and 11. The electrical stimulation will be applied with two 3x1 arrays of electrodes. The central stimulation electrodes will be positioned in F3 and CP3 (10-20 system). The AC stimulation will be one mA from the baseline to the stimulation peak. The stimulation will have a gamma sine waveform (80Hz) over the positive phase of the theta oscillation (between 4 and 8 Hz, adjusted by each subject, Reinhart et al, 2019) phase-locked between arrays with impedances always under 10 kOhm.

Treatment group

Traditional Cognitive Training Program BEHAVIORAL

Participants will start a cognitive intervention program identical to the intervention group. Still, unlike the intervention group, they will receive placebo electrical stimulation, i.e., an electrical current will be applied for a short period at the beginning of the session (30 seconds), and then the stimulation will be stopped. This procedure induces a sensation in the skin similar to the real stimulation without generating a detectable impact on the brain state. They will be performed in parallel to the cognitive intervention program in sessions 1, 2, 3, 4, 5, 7, 9, and 10.

Control group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or greater than 60 years.
• Presence of Mild Cognitive Impairment, according to the diagnostic criteria established in Petersen et al. (2014).
• Have six or more years of complete schooling (presence of reading and writing).

You may not qualify if:

• The previous diagnosis of other neurodegenerative diseases.
• Attending another cognitive training program.
• History of Epilepsy or current presence of epileptic seizures.
• Presence of psychiatric diseases.
• Presence of a relevant depressive picture (GDS \>=2).
• History of important neurological alterations such as the history of stroke, transient ischemic attack, cranial brain trauma.
• Important alterations of communication.

Sponsors & Collaborators

• Universidad del Desarrollo: lead

Study Sites (1)

Centro de Investigación del Desarrollo de Cognición y Lenguaje, Faculty of Medicine, Universidad de Valparaíso.

Valparaíso, Región de Valparaíso, 2520000, Chile

RECRUITING

Related Publications (13)

• Alekseichuk I, Turi Z, Amador de Lara G, Antal A, Paulus W. Spatial Working Memory in Humans Depends on Theta and High Gamma Synchronization in the Prefrontal Cortex. Curr Biol. 2016 Jun 20;26(12):1513-1521. doi: 10.1016/j.cub.2016.04.035. Epub 2016 May 26.

  PMID: 27238283 BACKGROUND

• Arango-Lasprilla JC, Rivera D, Aguayo A, Rodriguez W, Garza MT, Saracho CP, Rodriguez-Agudelo Y, Aliaga A, Weiler G, Luna M, Longoni M, Ocampo-Barba N, Galarza-Del-Angel J, Panyavin I, Guerra A, Esenarro L, Garcia de la Cadena P, Martinez C, Perrin PB. Trail Making Test: Normative data for the Latin American Spanish speaking adult population. NeuroRehabilitation. 2015;37(4):639-61. doi: 10.3233/NRE-151284.

  PMID: 26639932 BACKGROUND

• Babiloni C, Del Percio C, Pascarelli MT, Lizio R, Noce G, Lopez S, Rizzo M, Ferri R, Soricelli A, Nobili F, Arnaldi D, Fama F, Orzi F, Buttinelli C, Giubilei F, Salvetti M, Cipollini V, Franciotti R, Onofrj M, Stirpe P, Fuhr P, Gschwandtner U, Ransmayr G, Aarsland D, Parnetti L, Farotti L, Marizzoni M, D'Antonio F, De Lena C, Guntekin B, Hanoglu L, Yener G, Emek-Savas DD, Triggiani AI, Taylor JP, McKeith I, Stocchi F, Vacca L, Hampel H, Frisoni GB, De Pandis MF, Bonanni L. Abnormalities of functional cortical source connectivity of resting-state electroencephalographic alpha rhythms are similar in patients with mild cognitive impairment due to Alzheimer's and Lewy body diseases. Neurobiol Aging. 2019 May;77:112-127. doi: 10.1016/j.neurobiolaging.2019.01.013. Epub 2019 Jan 24.

  PMID: 30797169 BACKGROUND

• Constantinidis C, Klingberg T. The neuroscience of working memory capacity and training. Nat Rev Neurosci. 2016 Jul;17(7):438-49. doi: 10.1038/nrn.2016.43. Epub 2016 May 26.

  PMID: 27225070 BACKGROUND

• George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology. 2010 Jan;35(1):301-16. doi: 10.1038/npp.2009.87.

  PMID: 19693003 BACKGROUND

• Larrain-Valenzuela J, Zamorano F, Soto-Icaza P, Carrasco X, Herrera C, Daiber F, Aboitiz F, Billeke P. Theta and Alpha Oscillation Impairments in Autistic Spectrum Disorder Reflect Working Memory Deficit. Sci Rep. 2017 Oct 30;7(1):14328. doi: 10.1038/s41598-017-14744-8.

  PMID: 29085047 BACKGROUND

• Melloni M, Billeke P, Baez S, Hesse E, de la Fuente L, Forno G, Birba A, Garcia-Cordero I, Serrano C, Plastino A, Slachevsky A, Huepe D, Sigman M, Manes F, Garcia AM, Sedeno L, Ibanez A. Your perspective and my benefit: multiple lesion models of self-other integration strategies during social bargaining. Brain. 2016 Nov 1;139(11):3022-3040. doi: 10.1093/brain/aww231.

  PMID: 27679483 BACKGROUND

• Soto-Icaza P, Vargas L, Aboitiz F, Billeke P. Beta oscillations precede joint attention and correlate with mentalization in typical development and autism. Cortex. 2019 Apr;113:210-228. doi: 10.1016/j.cortex.2018.12.018. Epub 2019 Jan 2.

  PMID: 30677619 BACKGROUND

• Reinhart RMG, Nguyen JA. Working memory revived in older adults by synchronizing rhythmic brain circuits. Nat Neurosci. 2019 May;22(5):820-827. doi: 10.1038/s41593-019-0371-x. Epub 2019 Apr 8.

  PMID: 30962628 BACKGROUND

• Figueroa-Vargas A, Carcamo C, Henriquez-Ch R, Zamorano F, Ciampi E, Uribe-San-Martin R, Vasquez M, Aboitiz F, Billeke P. Frontoparietal connectivity correlates with working memory performance in multiple sclerosis. Sci Rep. 2020 Jun 9;10(1):9310. doi: 10.1038/s41598-020-66279-0.

  PMID: 32518271 BACKGROUND

• Billeke P, Armijo A, Castillo D, Lopez T, Zamorano F, Cosmelli D, Aboitiz F. Paradoxical Expectation: Oscillatory Brain Activity Reveals Social Interaction Impairment in Schizophrenia. Biol Psychiatry. 2015 Sep 15;78(6):421-31. doi: 10.1016/j.biopsych.2015.02.012. Epub 2015 Feb 19.

  PMID: 25861703 BACKGROUND

• Martin DM, Liu R, Alonzo A, Green M, Player MJ, Sachdev P, Loo CK. Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. Int J Neuropsychopharmacol. 2013 Oct;16(9):1927-36. doi: 10.1017/S1461145713000539. Epub 2013 May 30.

  PMID: 23719048 BACKGROUND

• Figueroa-Vargas A, Gongora B, Alonso MF, Ortega A, Soto-Fernandez P, Z-Rivera L, Ramirez S, Gonzalez F, Munoz Venturelli P, Billeke P. The effect of a cognitive training therapy based on stimulation of brain oscillations in patients with mild cognitive impairment in a Chilean sample: study protocol for a phase IIb, 2 x 3 mixed factorial, double-blind randomised controlled trial. Trials. 2024 Feb 23;25(1):144. doi: 10.1186/s13063-024-07972-7.

  PMID: 38395980 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Pablo Billeke, PhD

  Social Neuroscience and Neuromodulation Laboratory Director

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Begoña Gongora, PhD

CONTACT

+56 9 9438 5688; begona.gongora@uv.cl

Alejandra Figueroa, PhD(c)

CONTACT

+56 9 9819 48 60; amfigueroa@udd.cl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Social Neuroscience and Neuromodulation Laboratory Director

Study Record Dates

• First Submitted: February 28, 2022
• First Posted: March 22, 2022
• Study Start: January 26, 2022
• Primary Completion: September 21, 2023
• Study Completion: September 21, 2024
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)