Clinical trial NCT04328545: Transcranial Direct Current Stimulation Effect on Pain Threshold and Working Memory: Impact of Age and Protocol Type
Official title: Transcranial Direct Current Stimulation Effect on Pain Threshold and Working Memory in Healthy Adolescents, Young Adults and Elderly: a Randomized , Cross-over, Single Blind Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transcranial Direct Current Stimulation
Working Memory
Pain
Keywords: Age Groups
Pain Threshold
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2020-03-31
Enrollment: 30
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation method which has great potential as an aid in the therapeutic management of neuropsychiatric disorders and chronic pain syndromes. However, despite promising results, the response to stimulation presents great variability among subjects. Age is a factor that is known to influence the tDCS effect forging the inconsistency of clinical effect.The purpose of this study is to evaluate the effect of tDCS on pain perception and working memory in healthy women from 3 different age groups: adolescents, young adults and elderly. This is a randomized, single-blinded, cross-over study of 2 different active interventions and sham.

Detailed description: Transcranial direct current stimulation (tDCS) is a neuromodulation method that has great potential as an aid in the therapeutic management of neuropsychiatric disorders and chronic pain syndromes. tDCS modulates the neuronal membrane potential , facilitating neuronal depolarization or hyperpolarization, hence modifying the cortical excitability of the stimulated area. However, despite promising results the response to stimulation presents great variability among subjects. Chronological age is an important factor in the variation of brain plasticity. The dorsolateral prefrontal cortex (DLPFC) is associated with cognitive and emotional aspects of pain, in addition to being related to executive components of working memory. Anodal tDCS on DLPFC modulates pain level in patients with chronic pain and modifies working memory performance in healthy subjects and patients with memory impairment. The prefrontal cortex presents a great structural difference throughout lifespan: it is under maturational process in the adolescence, reaching peak of maturation in the adult life, and initiating process of cerebral senescence in elderly subjects. Therefore, the use of tDCS on DLPFC in these three age groups presents potential for a large variation in response. Faced with the potential of tDCS for adjuvant use in the treatment of several diseases, it is imperative to understand the variability of this intervention between different age groups. This knowledge may allow the optimization of neuromodulation protocols, allowing more careful and refined use in the clinic. The study primary outcomes is the difference between and within age groups on the variation of pre and post tDCS on pain threshold evaluated by Heath pain threshold on a Quantitative sensory testing paradigm and working memory performance evaluated by n-back test in healthy subjects of three age groups: adolescents, young adults, elderly. This is a randomized, single blinded, cross-over, sham-controlled clinical trial. The study will be conducted at the Clinical Research Center of the Hospital de Clínicas of Porto Alegre (HCPA). It will include 30 women, 10 women by age group: adolescents between 15 and 16 years,young adults between 30 and 40 years old and elderly women between 60 and 70 years. Participants will be randomized for a cross-over of three sessions: anodal stimulation in DLPFC, anodal stimulation in primary motor cortex (M1) as active control and sham stimulation.

Eligibility criteria: Inclusion Criteria:

* Age between 15 to 16 years for the adolescent group
* Age between 30 to 40 years for the young adult group
* Age between 60 to 70 years for the elderly group
* From completed elementary school to incomplete superior education
* right handed

Exclusion Criteria:

* Pregnancy
* Current smoker or previous smoker within 10 years
* Current Substance Use Disorder
* Neurological condition (e.g., traumatic brain injury, stroke, brain tumor, epilepsy, brain surgery, brain implant)
* Any diagnosed Psychiatric condition (e.g., Attention deficit/hyperactivity deficit (ADHD), bipolar disorder, major depressive disorder, schizophrenia, generalized anxiety disorder)
* Use of any antidepressive or psychoactive, psychostimulant medication
* Any chronic pain condition

Primary outcomes:
measure: Heat pain Threshold
timeFrame: percentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session
measure: Working memory performance
timeFrame: up to 60 minutes after tDCS onset
Secondary outcomes:
measure: Inhibitory control performance
timeFrame: up to 60 minutes after tDCS onset
measure: Area under the curve of the ERP during inhibitory control task
timeFrame: up to 60 minutes after tDCS onset
measure: Heat thermal threshold
timeFrame: percentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session
measure: Heat pain tolerance
timeFrame: percentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session
measure: Moderate pain
timeFrame: percentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session
measure: Unpleasantness sensation
timeFrame: percentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session
measure: Alpha wave power
timeFrame: up to 60 minutes after tDCS onset
measure: Beta wave power
timeFrame: up to 60 minutes after tDCS onset
measure: Theta wave power
timeFrame: up to 60 minutes after tDCS onset
measure: serum BDNF levels
timeFrame: up to 60 minutes before tDCS onset
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas e Porto Alegre (HCPA)
state: Rio Grande Do Sul
Study officials:
affiliation: Federal University of Rio Grande do Sul
name: Wolnei Caumo, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Scharinger C, Soutschek A, Schubert T, Gerjets P. When flanker meets the n-back: What EEG and pupil dilation data reveal about the interplay between the two central-executive working memory functions inhibition and updating. Psychophysiology. 2015 Oct;52(10):1293-304. doi: 10.1111/psyp.12500. Epub 2015 Aug 3.
citation: Boggio PS, Zaghi S, Lopes M, Fregni F. Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers. Eur J Neurol. 2008 Oct;15(10):1124-30. doi: 10.1111/j.1468-1331.2008.02270.x. Epub 2008 Aug 20.
citation: Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005 Sep;166(1):23-30. doi: 10.1007/s00221-005-2334-6. Epub 2005 Jul 6.
citation: Saldanha JS, Zortea M, Deliberali CB, Nitsche MA, Kuo MF, Torres ILDS, Fregni F, Caumo W. Impact of Age on tDCS Effects on Pain Threshold and Working Memory: Results of a Proof of Concept Cross-Over Randomized Controlled Study. Front Aging Neurosci. 2020 Jun 30;12:189. doi: 10.3389/fnagi.2020.00189. eCollection 2020.