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Trial registered on ANZCTR

Registration number

ACTRN12614000817640

Ethics application status

Approved

Date submitted

14/07/2014

Date registered

31/07/2014

Date last updated

31/07/2014

Type of registration

Retrospectively registered

Titles & IDs

Public title

How does anodal transcranial direct current stimulation of the pain neuromatrix affect brain excitability and pain perception? A randomised, double-blind, sham control study

Scientific title

The effects of anodal transcranial direct current stimulation on primary motor cortex, primary sensory cortex, and dorsolateral prefrontal cortex excitability in healthy individuals.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Healthy participants- Area of research: Pain perception and the level of brain excitability

Condition category

Condition code

Neurological

Studies of the normal brain and nervous system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Transcranial direct current stimulation (tDCS), including anodal (a-tDCS) and cathodal (c-tDCS), is intervention in the current project.
Since it is a new technique, the optimal parameters is unclear yet. Based on the literature, the safe current density should be less than 0.054 mV/cm2 and the duration of application should be less than 40 min.
In the current project, healthy participants received intervention with tDCS under each of five different conditions in a random order: a-tDCS of primary motor cortex , a-tDCS of primary sensory cortex, a-tDCS of dorsolateral prefrontal cortex, sham a-tDCS, and no tDCS. The experimental sessions were separated by at least 72 hours to avoid interference or carry-over effects of tDCS, and completed at the same time of day to avoid diurnal variation. The duration of tDCS application was 20 minutes with amplitude of 0.3 mA and electrode size of 1.5 * 2 cm ( current density of 0.029 mV/cm2) in all experiments.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

Sham transcranial direct current stimulation is the placebo treatment. In Sham transcranial direct current stimulation, the electrodes will be placed on the brain and the device will be turned on just for 30 second. The feeling of participants is completely similar to real (active) transcranial direct current stimulation sessions but in sham condition, there is no treatment effect.

Control group

Placebo

Outcomes

Primary outcome [1]

The main outcome measure is the level of brain excitability in primary motor cortex. To measure the level of primary motor cortex excitability, we will use Transcranial magnetic stimulation on the primary motor cortex area and record the EMG activity of First dorsi interossous (FDI) muscle. The peak to peak amplitude of motor evoked potentials recorded from FDI muscle indicates the level of primary motor cortex excitability.

Timepoint [1]

All evaluations will be performed before (Tpre), immediately after (T0), 30 min (T30) and 60 min (T60) after the intervention. Also, one day after the intervention all evaluations will be repeated (Tday1).

Primary outcome [2]

The second primary outcome measure is the level of excitability in primary sensory cortex. To measure the level of excitability in the primary sensory cortex sensory evoked potential (SEP) will be measured. and the peak to peak amplitude of N20-P25 responses generated in primary sensory cortex will be measured.

Timepoint [2]

Secondary outcome [1]

Sensory threshold (STh) to electrical stimulation. Electrical stimulation will be applied by a pen electrode (model: 2762CC, Chattanooga, USA) to the right median nerve (pulse duration: 200 microsecond) at wrist level. Current supply will start at 0mA and will be increased in steps of 0.1mA until the participant reports sensation and pain. The intensity of current at which perception of the electrical stimulus is first reported will be taken as the STh.

Timepoint [1]

Secondary outcome [2]

Pain threshold (PTh) to electrical stimulation. Electrical stimulation will be applied by a pen electrode (model: 2762CC, Chattanooga, USA) to the right median nerve (pulse duration: 200 microsecond) at wrist level. Current supply will start at 0mA and will be increased in steps of 0.1mA until the participant reports sensation and pain. The intensity of current at which participants first reported pain will be taken as the PTh.

Timepoint [2]

Secondary outcome [3]

Pain threshold to the mechanical stimulation (PpTh): Pressure was induced using a pressure algometer (model: FDX 50, Wagner, USA; capacity: 50× 0.05Ibf, accuracy: ±0.3% of full scale) with a flat circular metal probe dressed in a plastic cover. Force was displayed digitally in increments of 0.1N. The algometer was mounted vertically. For each measurement the algometer was calibrated to enable force to be applied at a controlled and steady rate. PpTh was defined as the amount of force required to elicit a sensation of pain distinct from pressure or discomfort. The PpTh measurement point was marked in the middle of the belly of the FDI muscle.

Timepoint [3]

Eligibility

Key inclusion criteria

All participants should be:
_ Healthy
- Right-handers as determined by the Edinburgh Handedness Inventory
_ between 18 and 49 years

Minimum age

18 Years

Maximum age

49 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

volunteers will be excluded if they have:
- Clinically significant or unstable medical, neuropsychiatric
- Chronic pain disorder
- History of substance abuse or dependence
- Any use of central nervous system-effective medication
- History of brain surgery, tumour, or intracranial metal implantation
- All participants will be interviewed and examined by a physician prior to enrolment in the study and provided written, informed consent.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Potential participants contacted the researcher by phone or email. Following this, those who wished to be sent explanatory statements and consent forms volunteer their additional contact details.
Based on the medical history forms answered by the volunteers, individuals who had no neurological or orthopaedics problem were selected and referred to the physician to be sure that application of tDCS is safe for the volunteers. Then, the second researcher allocated a number for each participants. The order of intervention sessions and the order of measuring of the outcome measures were randomized by sealed opaque envelopes.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Type of endpoint/s

Statistical methods / analysis

A two-way repeated measures ANOVA was used to assess the effects of two independent variables, site of stimulation (S1, M1, and DLPFC) and time point (Tpre, T0, and T30), on MEPs, SEPs, STh, PTh and PpTh. Mauchly’s test was used to assess the validity of the sphericity assumption for repeated measures ANOVA; it requires that the variances for each set of difference scores be equal. Greenhouse-Geisser corrected significance values were used when sphericity was lacking. Additionally, to test whether the baseline value of each stimulation site differed significantly from post-intervention time points (T0, T30), a paired-sample t-test was applied.
A significance level of P = 0.05 was adopted for all comparisons. A post-hoc test (Bonferroni) was performed where indicated. Means are reported +/- SE. Statistical analyses were performed using SPSS software version 22.

Clinically, a minimum of a 20% difference between the level of excitability before and after the intervention is needed to be sure that the intervention is effective (the magnitude of the difference between a null hypothesis and a true alternative hypothesis).
As a result, to calculate the sample size, we run a pilot study and measured the level of M1 and S1 excitability. Regarding the Power based sample size formula, the number of participants was calculated. In the current study, the power was 0.9 and Alpha was 0.05.
Based on the formula, the minimal needed participants was 11 and we recruited 12 healthy individuals.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

7/10/2013

Actual

7/10/2013

Date of last participant enrolment

Anticipated

10/02/2014

Actual

10/02/2014

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Bita Vaseghi

Address [1]

Building b, peninsula Campus, Monash University, Frankston, VIC, Australia
Postcode: 3199
P.O. Box: 527

Country [1]

Australia

Primary sponsor type

Individual

Name

Shapour Jaberzadeh

Address

Building b, peninsula Campus, Monash University, Frankston, VIC, Australia
Postcode: 3199
P.O. Box: 527

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash University Human Research Ethics Committee (MUHREC)

Ethics committee address [1]

Postal – Monash University, Vic 3800, Australia
Building 3E, Room 111, Clayton Campus, Wellington Road, Clayton

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

13/11/2012

Ethics approval number [1]

CF12/2383 - 2012001295

Summary

Brief summary

Pain is the primary reason for patients to seek medical care. A survey found that 31% of the population in the united state and 19% of adult European population had experienced moderate to severe pain, with serious consequences for their social and working lives. The exorbitant medical treatment costs paid by governments and individuals can be decreased by better therapeutic approaches.
Parallel areas of brain are involved in experience of Pain which make it a  complex issue to manage. Lateral parallel nuclei and somatosensory cortex (S1) are responsible for discrimination of quality, location, and intensity of pain, whereas medical thalamic nuclei, dorsolateral prefrontal cortex (DLPFC), and limbic system have been proposed to subserve emotional dimensions of pain. Furthermore, it is suggested that neural communications between S1 and primary motor cortex (M1) may leads to motor cortex neuroplastisity  to reduce movement in order to prevent further injuries.
Non-invasive therapeutic approaches, including medication, electrotherapy, and manual therapy, can provide satisfactory pain control in only 20%-30% of cases of pain syndromes. In order to develop a more effective treatment method, it is therefore, needed to test other efficient methods. Transcranial direct current stimulation (tDCS), including anodal and cathodal tDCS, is one of the novel painless techniques used by neuroscientists to relieve pain. The optimal parameters, stimulation site and current density, for effective application of tDCS,  have not been studied yet. The findings of current study will be used to optimise the effects of new therapeutic approaches for pain relief.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Ms Bita Vaseghi

Address

School of Primary Health Care
Faculty of Medicine, Nursing and Health Sciences
Monash University Peninsula Campus
Building B
PO BOx 527
Frankston 3199, VIC

Country

Australia

Phone

+61 3 9904 4827

Fax

+61 3 9904 4812

[email protected]

Contact person for public queries

Name

Bita Vaseghi

Address

School of Primary Health Care
Faculty of Medicine, Nursing and Health Sciences
Monash University Peninsula Campus
Building B
PO BOx 527
Frankston 3199, VIC

Country

Australia

Phone

+61 3 9904 4816

Fax

[email protected]

Contact person for scientific queries

Name

Bita Vaseghi

Address

School of Primary Health Care
Faculty of Medicine, Nursing and Health Sciences
Monash University Peninsula Campus
Building B
PO BOx 527
Frankston 3199, VIC

Country

Australia

Phone

+61 3 9904 4816

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Differential effects of cathodal transcranial direct current stimulation of prefrontal, motor and somatosensory cortices on cortical excitability and pain perception - a double-blind randomised sham-controlled study.	2015	https://dx.doi.org/10.1111/ejn.13043
Embase	How does anodal transcranial direct current stimulation of the pain neuromatrix affect brain excitability and pain perception? A randomised, double-blind, sham-control study.	2015	https://dx.doi.org/10.1371/journal.pone.0118340
Embase	The effects of anodal-tDCS on corticospinal excitability enhancement and its after-effects: Conventional vs. unihemispheric concurrent dual-site stimulation.	2015	https://dx.doi.org/10.3389/fnhum.2015.00533
Embase	Unihemispheric concurrent dual-site cathodal transcranial direct current stimulation: The effects on corticospinal excitability.	2016	https://dx.doi.org/10.1111/ejn.13229

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically