Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial registered on ANZCTR
Registration number
ACTRN12618001719224
Ethics application status
Approved
Date submitted
5/10/2018
Date registered
18/10/2018
Date last updated
20/05/2021
Date data sharing statement initially provided
20/05/2021
Type of registration
Prospectively registered
Titles & IDs
Public title
The Effects of Brain Training Using Infraslow Neurofeedback on the Autonomic Nervous System
Query!
Scientific title
The Effects of Infraslow Neurofeedback on the Autonomic Nervous System in a Healthy Population: a randomised, double-blind, placebo-controlled, pilot study
Query!
Secondary ID [1]
296265
0
Nil known
Query!
Universal Trial Number (UTN)
U1111-1216-4452
Query!
Trial acronym
ISANS
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Dysautonomia
309944
0
Query!
Condition category
Condition code
Neurological
308717
308717
0
0
Query!
Studies of the normal brain and nervous system
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
20 healthy men and 20 healthy women between the ages of 18-60 will be recruited from the from the community. Recruitment will be via advertisement on notice boards and in local newspapers over a 6 months period with an invitation to participate in a potential therapeutic method to modulate the ANS. Individuals who contact the researchers will be emailed an information sheet to read over before meeting the investigators. Individuals who show an interest will be asked to attend a screening session at the clinic of the University Hospital of Otago, Dunedin. Initially, potential participants will be assessed to see if they meet the inclusion criteria and do not have any existing exclusion criteria. Recruitment of participants will continue until the sample size of 20 for both men and women is achieved.
Those who are eligible (n=20 men, n=20 women) will be randomised to either i) real infraslow neurfeedack (ISF; n=10 men, n=10 women) or ii) placebo ISF (P-ISF; n=10 men, n=10 women). Participants will receive a total of 6 sessions of ISF/P-ISF. An EEG and a battery of ANS assessments will be performed at screening (T0), prior to and following their first ISF/P-ISF session (T1) and last ISF/P-ISF session (T6), 1 week post ISF/P-ISF (T7), 1 month post ISF/P-ISF (T8) and 3 months post ISF/P-ISF (T9). In addition, all participants will fill out questionnaires and perform brief tests (i.e. Stroop tests) assessing various aspects of health including sleep, stress, well-being, affect and cognition (T0, T6, T7, T8 & T9). Furthermore, they will be asked to perform at-home collection of saliva samples on 2 consecutive weekdays following each ANS testing session (T0, T1, T6, T7, T8 & T9).
Infraslow neurofeedback (ISF) is a non-invasive technique that measures brain activity using electroencephalogram (EEG) and generate a sound when your brain exhibits the targeted infraslow brain activity. EEG uses small electrodes or metal discs placed on scalp to measure, track and record changes in the brain’s electrical activity. Participants will complete a total of 6 ISF/P-ISF sessions. Training will be administered in a hospital setting by a doctor/researcher with prior experience and training delivering Brainmaster Inc. ISF/P-ISF training. There will be 3 sessions a week for 2 weeks. Each session will be 20 minutes with the exception of the first session which will be only 10 minutes. sLORETA ISF/P-ISF will be implemented with a 24 channel DC coupled amplifier produced by Brainmaster Inc. Training will be administered with participants sitting in a comfortable chair with their eyes closed. After careful skin preparation, the appropriate Comby EEG cap (Ag/AgCl) will be placed on the participant’s head with reference electrodes at the mastoids. The impedances of the active electrodes will be kept below 5 kilo-ohms. Before the training period, participants will be instructed to relax and listen to the sound being played. A distinct tone will be used for ISF reinforcement at the dorsal anterior cingulate cortex (dACC). Reward threshold will be adjusted in real time at above 90%. In other words, for 90% of the time, a sound will be played (reward) when the participant’s brain activity meets the infraslow magnitude (threshold).
Prior to their first training session, a simple explanation will be given to participants. They will be informed that research has shown that attenuation of sympathetic nervous system activity may be of health benefit and that the sound they hear during ISF/P-ISF reflects whether they are doing well. There will be a total of 10 clinic visits in order to assess primary and secondary outcome measures both pre and post intervention. Sessions will run from 30 minutes to 2 hours depening on the assessments and interventions employed.
Researchers will maintain contact via email throughout the trial to help ensure protocol adherence. A Case Report Form (CRF) will be used for the purposes of recording participant specific data including the number of sessions attended. The researchers will compare baseline characteristics between those who complete the trial and those who do not in order to help inform strategies for improved compliance in the event larger trials are performed.
Query!
Intervention code [1]
312615
0
Treatment: Devices
Query!
Comparator / control treatment
P-ISF will be given to half of our healthy participants (n=10 men and n=10 womenn) who will act as our control groups. The instructions given to P-ISF participants will be identical to those who receive ISF, however, for P-ISF, the simulation protocol by Brainmaster Inc will be administered. The simulation protocol will play the distinct tone at random. thereby not reinforcing changes in infraslow activity.
Query!
Control group
Placebo
Query!
Outcomes
Primary outcome [1]
307692
0
Salivary cortisol (cortisol diurnal slope),
Salivary diurnal cortisol will be assessed on 2 consecutive weekdays following each ANS testing session through at-home collection of saliva upon waking and at bedtime using the passive drool method of saliva collection. Whole saliva samples will be collected with 0.5ml non-sterile microcentrifuge tubes (sourced from Interlab LTD, Wellington, NZ). Participants will receive written and verbal instructions regarding standard collection and storage protocol. All samples will be analysed in the Diabetes and Lipid Laboratory of the Department of Nutrition at the University of Otago (Dunedin, NZ).
Query!
Assessment method [1]
307692
0
Query!
Timepoint [1]
307692
0
Following T0(screening), T1 (1st ISF/P-ISF session), T6 (last ISF/P-ISF session), T7 (1 week post ISF/P-ISF; primary endpoint), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF). Saliva samples are collected on the first two consecutive weekdays following their clinic visit.
Query!
Primary outcome [2]
307693
0
Galvanic skin response {Primary Outcome]
Galvanic skin response (GSR) will be assessed with bipolar finger electrodes [MLT118F GSR finger electrodes; FE116 GSR Amplifier, ADInstruments]. A stimulus is required to stimulate sudomotor activity, therefore participants will be asked to perform an inspiratory gasp and the change in electrical conductance from baseline will be recorded.
Query!
Assessment method [2]
307693
0
Query!
Timepoint [2]
307693
0
T0(screening), T1 (immediately pre and post 1st ISF/P-ISF session), T6 (immediately pre and post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF; primary endpoint), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF).
Query!
Primary outcome [3]
307694
0
Cardiovascular autonomic nervous system function (heart rate/heart rate variability/blood pressure/heart rate recovery) [Primary Outcome]
Heart rate & blood pressure will be measured and their responses assessed at rest (6 minutes), during changes in breathing pattern (paced breathing at 15 breaths per minute for 6 minutes and deep breathing paced at 6 breaths per minute for 6-8 breaths), and during and following a Valsalva manoeuvre. Heart rate is measured with a standard limb lead (lead II) electrocardiogram, beat-to-beat blood pressure with finger-photoplethysmography [Finometer Midi (regularly calibrated with automated sphygmomanometer; Connex ProBP 3400 series Welch Allyn)], and respiratory rate with a respiratory belt transducer placed around the chest. The pressure and time of the strain during the Valsalva manoeuvre is recorded with a calibrated pressure transducer. Heart variability is calculated using the a commercially avaliable HRV module in Labchart 8 (ADInstruments,Dunedin, NZ) using standard frequency and time domain analysis. All cardiovascular primary outcome measures are collected simultaneously with an analogue-to-digital converter (Powerlab/3508/P).
To assess heart rate recovery, participants will perform a maximal incremental exercise test on a cycle ergometer (Model: E100 P, COSMED), while HR, BP, ECG and metabolic variables [VO2, VCO2, and R (i.e., VCO2/ VO2); Quark CPET, COSMED)] are monitored and measured at each stage. The protocol will start at 50w and increased at a magnitude of 25w or 50w (individualized for each participant) every 2 min, until volitional exhaustion. During recovery participants will remain quietly seated on the cycle while maintaining an upright posture as ECG, BP and respiration are monitored for 5-6 minutes.
Query!
Assessment method [3]
307694
0
Query!
Timepoint [3]
307694
0
T0(screening), T1 (immediately pre and post 1st ISF/P-ISF session), T6 (immediately pre and post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF; primary endpoint), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF). Note: heart-rate recovery will only be assessed at T0(screening), T7 (1 week post ISF/P-ISF; primary endpoint)
Query!
Secondary outcome [1]
352639
0
Resting-state brain activity
Resting state EEG will be sampled continuously at 500 Hz using a Mitsar-EEG 202 DC amplifier. Briefly, EEG will be recorded with 19 electrodes (Fp1, Fp2, F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4, P8, O1 O2) according to the 10-20 placement. Linked mastoids reference will be used and all electrode impedances kept below 5 kO. EEGs will be recorded with participants sitting upright in a comfortable chair with their eyes closed. All EEGs will be recorded for 6 minutes. Raw data will be resampled at 128 Hz, filtered from 0.001 Hz to 44 Hz, plotted, and carefully inspected for manual artefact rejection on EEGLAB. Subsequently, average cross-spectral matrices will be computed for bands infraslow (0.01-0.1 Hz), delta (2-3.5 Hz), theta (4-7.5Hz), alpha (8-12 Hz), beta (12.5-30Hz) and gamma (30.5-44 Hz).
Query!
Assessment method [1]
352639
0
Query!
Timepoint [1]
352639
0
T0(screening), T1 (immediately pre and post 1st ISF/P-ISF session), T6 (immediately pre and post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF).
Query!
Secondary outcome [2]
352644
0
Perceived Stress Scale (PSS)
The PSS is a 10-item scale assessing the perception of stress.
Query!
Assessment method [2]
352644
0
Query!
Timepoint [2]
352644
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Secondary outcome [3]
352648
0
World Health Organization 5 (WHO-5) Well-being index
The WHO-5 has 5 items assessing aspects of wellbeing.
Query!
Assessment method [3]
352648
0
Query!
Timepoint [3]
352648
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Secondary outcome [4]
352649
0
Behavioural Inhibition and Activation Scale (BIS/BAS)
The BIS/BAS assesses aversive and appetative motives.
Query!
Assessment method [4]
352649
0
Query!
Timepoint [4]
352649
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Secondary outcome [5]
352650
0
Pittsburgh Sleep Quality Index (PSQI)
The PSQI is a 19-item questionnaire used to identify sleep disturbances
Query!
Assessment method [5]
352650
0
Query!
Timepoint [5]
352650
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Secondary outcome [6]
352651
0
Positive and Negative Affect Schedule (PANAS-GEN)
The PANAS-GEN consists of two 10-item scales to assess positive and negative affect
Query!
Assessment method [6]
352651
0
Query!
Timepoint [6]
352651
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Secondary outcome [7]
352652
0
Stroop Test
The Stroop Test assesses the ability to inhibit cognitive interference.
Query!
Assessment method [7]
352652
0
Query!
Timepoint [7]
352652
0
T0(screening), T6 (immediately post last ISF/P-ISF session), T7 (1 week post ISF/P-ISF), T8 (1 month post ISF/P-ISF), and T9 (3 months post ISF/P-ISF)
Query!
Eligibility
Key inclusion criteria
1. Men and women aged 18-60 years. With respect to our female participants, only women currently using monophasic hormonal contraception will be recruited as hormonal fluctuations that occur during the menstrual cycle are known to alter ANS function.
2..Right handedness as handedness affects EEG interpretation.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
60
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
Yes
Query!
Key exclusion criteria
1. Certain medications (e.g. antidepressants and other psychotic medications)
2. Recent significant head injuries. e.g. concussion where consciousness is lost or surgery
3. Psychiatric disorders with psychotic symptoms or manic symptoms
4. Other health problems – diabetes, cancer, heart disease, uncontrolled hypertension
5. History of epilepsy
6. Metal implants or implanted electronics (pacemaker)
7. Recurring headaches
8. Currently pregnant
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An independent researcher from the department will seal each allocation in a consecutively numbered opaque envelope before handing them to the enrolling researcher. During enrolment and randomisation of a new participant, the enrolling researcher will write the participant's ID before opening the sealed envelope and retrieving the allocation from inside.
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a validated randomisation program utilised by clinical trial researchers. To ensure balanced sample size across the placebo and ISF groups over time, block randomisation will be performed.
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Not Applicable
Query!
Type of endpoint/s
Safety
Query!
Statistical methods / analysis
Alterations in ANS with ISF/P-ISF be investigated and quantified from the aforementioned battery of tests. These dependent variables will then be statistically compared using mixed 2-way repeated measures ANOVA. The direction and the magnitude of change in the dependent variables will inform the underpinning change in ANS function and whether it is clinically meaningful.
sLORETA will be used to perform a voxel by voxel analysis for the different frequency bands of the current density distribution to identify potential differences in brain electrical activity between the two groups at baseline, after one, six sessions and one week follow-up. Non-parametric statistical analyses of functional sLORETA images (SnPM) will be performed for each contrast using sLORETA’s build-in voxel wise randomisation test (5000 permutations) and employing a log-F-ratio statistic for independent groups with a threshold of p<0.05.
To date, this is the first study examining the effect of ISF on the ANS in healthy individuals, thus no formal power calculations were made.
Query!
Recruitment
Recruitment status
Stopped early
Query!
Data analysis
No data analysis planned
Query!
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Query!
Date of first participant enrolment
Anticipated
1/11/2018
Query!
Actual
1/01/2019
Query!
Date of last participant enrolment
Anticipated
1/05/2019
Query!
Actual
1/06/2019
Query!
Date of last data collection
Anticipated
1/08/2019
Query!
Actual
1/06/2019
Query!
Sample size
Target
40
Query!
Accrual to date
Query!
Final
30
Query!
Recruitment outside Australia
Country [1]
20900
0
New Zealand
Query!
State/province [1]
20900
0
Otago
Query!
Funding & Sponsors
Funding source category [1]
300859
0
Charities/Societies/Foundations
Query!
Name [1]
300859
0
Neurological Foundation
Query!
Address [1]
300859
0
66 Grafton Road, Grafton
PO Box 110022
Auckland Hospital
Auckland, New Zealand
1148
Query!
Country [1]
300859
0
New Zealand
Query!
Primary sponsor type
Individual
Query!
Name
Professor Dirk De Ridder
Query!
Address
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country
New Zealand
Query!
Secondary sponsor category [1]
300412
0
Individual
Query!
Name [1]
300412
0
Dr Tyson Perez
Query!
Address [1]
300412
0
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country [1]
300412
0
New Zealand
Query!
Other collaborator category [1]
280382
0
Individual
Query!
Name [1]
280382
0
Dr Luke Wilson
Query!
Address [1]
280382
0
University of Otago
Department of Medicine
201 Great King St
Dunedin, 9016
Query!
Country [1]
280382
0
New Zealand
Query!
Other collaborator category [2]
280391
0
Individual
Query!
Name [2]
280391
0
Dr Sook Ling Leong
Query!
Address [2]
280391
0
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country [2]
280391
0
New Zealand
Query!
Other collaborator category [3]
280392
0
Individual
Query!
Name [3]
280392
0
Assoc. Professor Sven Vanneste
Query!
Address [3]
280392
0
University of Texas at Dallas
School of Behavioral and Brain Sciences,
800 W Campbell Rd, Richardson, TX 75080,
Query!
Country [3]
280392
0
United States of America
Query!
Other collaborator category [4]
280393
0
Individual
Query!
Name [4]
280393
0
Mark Smith
Query!
Address [4]
280393
0
Neurofeedback Services of New York,
140 West 79th Street, #2B
New York, NY 10024
Query!
Country [4]
280393
0
United States of America
Query!
Ethics approval
Ethics application status
Approved
Query!
Ethics committee name [1]
301634
0
Southern Health and Disability Ethics Committee
Query!
Ethics committee address [1]
301634
0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Query!
Ethics committee country [1]
301634
0
New Zealand
Query!
Date submitted for ethics approval [1]
301634
0
17/09/2018
Query!
Approval date [1]
301634
0
04/10/2018
Query!
Ethics approval number [1]
301634
0
18/STH/187
Query!
Summary
Brief summary
The autonomic nervous system is vital for regulating ‘automatic’ functions of your body such as heart rate, blood pressure and the release of hormones. It is generally composed of two main branches; the sympathetic (fight or flight) and parasympathetic (rest and digest) systems. An imbalance in these two systems is termed 'dysautonomia' and is associated with numerous diseases.
Our research group is undertaking a clinical trial in healthy adults that will investigate the effectiveness of a novel type of therapy known as infraslow neurofeedback in the regulation of the autonomic nervous system. Infraslow neurofeedback is a completely non-invasive therapy whereby we monitor the brain’s electrical activity with a device called an EEG. Through real-time feedback, participants essentially learn to self-regulate their brain activity with the aid of ‘rewards’ in the form of pleasant sounds given when their brain displays the desired activity (i.e. less or more infraslow activity). This type of learning which incorporates immediate feedback and positive reinforcement is known as operant conditioning. By teaching people to self-regulate the activity of very specific regions of the brain involved in controlling their autonomic nervous system, our hope is that we will see an improvement in the balance between the sympathetic and parasympathetic branches. As far as we know, we are the first in the world to study the potential effects of infraslow training on the autonomic nervous system.
Query!
Trial website
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
87606
0
Prof Dirk De Ridder
Query!
Address
87606
0
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country
87606
0
New Zealand
Query!
Phone
87606
0
+64 3 470 9337
Query!
Fax
87606
0
Query!
Email
87606
0
[email protected]
Query!
Contact person for public queries
Name
87607
0
Dr Tyson Perez
Query!
Address
87607
0
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country
87607
0
New Zealand
Query!
Phone
87607
0
+64 03 474 0999 (ext 58847)
Query!
Fax
87607
0
Query!
Email
87607
0
[email protected]
Query!
Contact person for scientific queries
Name
87608
0
Prof Dirk De Ridder
Query!
Address
87608
0
University of Otago
Department of Surgical Sciences, Neurosurgery
201 Great King St
Dunedin, 9016
Query!
Country
87608
0
New Zealand
Query!
Phone
87608
0
+64 3 470 9337
Query!
Fax
87608
0
Query!
Email
87608
0
[email protected]
Query!
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Doc. No.
Type
Citation
Link
Email
Other Details
Attachment
11731
Ethical approval
376137-(Uploaded-09-11-2018-08-25-52)-Study-related document.pdf
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
No additional documents have been identified.
Download to PDF