Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000348752
Ethics application status
Approved
Date submitted
22/02/2022
Date registered
25/02/2022
Date last updated
25/02/2022
Date data sharing statement initially provided
25/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Testing the effect of a new brain stimulation technique on memory and function in people with early Alzheimer’s disease and amnestic mild cognitive impairment.
Scientific title
Exploring the effect of a novel brain stimulation technique on cognitive function in people with early Alzheimer’s disease and amnestic mild cognitive impairment- A double-blinded randomised placebo-controlled delayed-start pilot study
Secondary ID [1] 306491 0
None
Universal Trial Number (UTN)
U1111-1274-7089
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Alzheimer's Disease
 325354 0
Amnestic Mild Cognitive Impairment 325355 0
Condition category
Condition code
Neurological 322738 322738 0 0
Alzheimer's disease
Neurological 322768 322768 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High definition transcranial infraslow grey noise stimulation (HD-tIGNS) will be administered four times a week (30 min/session) for a total of 10 weeks (i.e., 40 sessions) by the researcher experienced in administering neuromodulation techniques. There are two arms of the study, namely a delayed start group and an early start group. Participants in the delayed start group will receive 5 weeks of sham stimulation, followed by 5 weeks of active stimulation. Participants in the early start group will receive 10 weeks of active stimulation.

The Starstim32 TCS device (Neuroelectrics, Spain) will be used to deliver stimulation while participants are comfortably and quietly seated. Stimulation electrodes will be placed identically during both the active stimulation phase and the sham stimulation phase, to target the anti-correlated activity of the key hubs of the triple network model (the salience network, the default mode network, the central executive network).

For the active stimulation phase, the HD-tIGNS will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and the end of each stimulation session, with continuous stimulation in between.

Adherence to the intervention will be recorded by the treating therapist and will be summarized as the percentage of the total number of sessions.
Intervention code [1] 322917 0
Treatment: Devices
Comparator / control treatment
For the sham stimulation phase, to create an identical skin sensation to the active stimulation, the actisham waveform developed by the Neuroelectrics will be used. The current will be applied for a 60s ramp up and 60s ramp down at the beginning and the end of each stimulation session respectively, without any current for the remainder of the stimulation period. This actisham procedure has been used previously and is shown to effectively blind participants to the stimulation condition, as it can induce the same scalp sensations perceived during active stimulation, both in terms of intensity and localization, while preventing currents from reaching the cortex and causing changes in brain excitability.
Control group
Placebo

Outcomes
Primary outcome [1] 330541 0
Feasibility measures:
• Recruitment rate, i.e., number of participants per month
• Proportion of participants recruited from the total number screened (with reasons for exclusion) and expressed as a percentage.
• Adherence to intervention measured as number of treatment sessions attended by each participant and expressed as a percentage of the total number of sessions.
• Drop-out rates, measured as the number of participants who dropped-out in each group, and expressed as a percentage of the total number of participants enrolled in the study.

Feasibility measures will be recorded by PI on a weekly basis, since the release of the advertisements, and the number of advertisements will also be recorded.
Timepoint [1] 330541 0
Throughout the study period
Primary outcome [2] 330542 0
Safety measures: Any adverse events or side effects (e.g. tingling or burning under stimulation electrodes).


The following variables will be recorded:
•Qualitative description of each symptom
•The intensity of each symptom will be measured using a Likert scale ranging from 0 (none) to 10 (extreme)
•Relation of the symptom to the treatment, measured on a scale ranging from 1 (unrelated) to 5 (strongly related).
•Duration of each symptom and the time taken for resolution of each symptom, expressed in minutes.
•Worsening or improvement of symptoms compared to the status prior to the previous session.
•Any drop-outs due to adverse effects will also be recorded.
Timepoint [2] 330542 0
During each intervention sessions, and immediately post two intervention periods (i.e., at 5 weeks and at 10weeks).
Primary outcome [3] 330543 0
Cognitive tests:

Montreal Cognitive Assessment and Mini- Mental State Examination, and

CANTAB test battery for early AD
• Motor Screening Task
• Reaction Time
• Paired Associates Learning
• Spatial Working Memory
• Pattern Recognition Memory
• Delayed Matching to Sample
• Rapid Visual Information Processing
Timepoint [3] 330543 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and at 10 weeks)
Secondary outcome [1] 406567 0
Alzheimer's Disease Functional Assessment and Change Scale
Timepoint [1] 406567 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [2] 406568 0
European Quality of Life–5 Dimensions
Timepoint [2] 406568 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [3] 406569 0
World Health Organisation- Five Well-Being Index
Timepoint [3] 406569 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [4] 406570 0
State-Trait Anxiety Inventory
Timepoint [4] 406570 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [5] 406571 0
Intolerance of Uncertainty Scale - Short Form
Timepoint [5] 406571 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [6] 406572 0
Medical Outcomes Study-Sleep Scale
Timepoint [6] 406572 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)
Secondary outcome [7] 406574 0
Resting-state Electroencephalography (EEG) (Current source density and functional connectivity at the targeted triple network brain regions)
Timepoint [7] 406574 0
Baseline and immediately post two intervention periods (i.e., at 5 weeks and 10 weeks)

Eligibility
Key inclusion criteria
To be included in the study, participants must meet all of the following inclusion criteria:
• Capable of understanding and signing an informed consent form, as assessed by the informed consent questionnaire.
• A diagnosis of ‘probable’ or ‘possible’ Alzheimer’s disease based on National Institute on Aging and Alzheimer’s Association (NIA-AA) guidelines or a diagnosis of amnestic mild cognitive impairment
• A score of 0.5-1 in the Clinical Dementia Rating scale
• A score of 72 points or higher on the Addenbrooke’s Cognitive Examination (ACE-III, a screening instrument for dementia)
• A score higher than 18 points in the Mini-Mental State Exam (MMSE)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following conditions will be excluded:
• History of epilepsy or seizures
• History of stroke or tumour
• Unstable medical or psychiatric conditions
• Presence of any pacemaker or defibrillator
• Presence of any metal implant in the body
• Alcohol or substance abuse
• Dyslipidaemia
• History of uncontrolled/untreated hypertension
• Participants who, in the opinion of the investigators, do not understand the information and procedures of the study, or would not be compliant with them.
• Any participant for whom the investigators believe, for any reason, that participation would not be an acceptable risk.

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)
A research administrator, not involved in the treatment or assessment procedures, will randomise eligible volunteers using an open-access randomization software program, to start with either: a) HD-tIGNS, or b) Sham stimulation.

The randomisation schedule will be concealed in a number sealed and opaque envelopes and provided to the participants at their baseline measurements.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
This pilot study is a delayed-start double-blinded (participant and assessor) randomized sham-controlled trial, with two arms (Early start and Delayed start) and the outcome measures recorded at baseline (T0), and after the two intervention periods (T1 i.e., at 5 weeks and T2 i.e., at 10 weeks).

Participants in the delayed start group will receive 5 weeks of sham stimulation, followed by 5 weeks of active stimulation. Participants in the early start group will receive 10 weeks of active stimulation.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
SPSS version 22.0 will be used for all statistical analyses. Descriptive statistics will be used to analyse feasibility and safety measures. Percentage change to baseline will be calculated for the primary and secondary measures. Simple statistical analysis (student’s t-test) will be used to obtain estimates of the intervention effects on cognitive, functional, quality of life and secondary outcome measures.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/03/2022
Actual
Date of last participant enrolment
Anticipated
29/09/2023
Actual
Date of last data collection
Anticipated
29/12/2023
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 24598 0
New Zealand
State/province [1] 24598 0
Otago

Funding & Sponsors
Funding source category [1] 310836 0
University
Name [1] 310836 0
University of Otago
Country [1] 310836 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
PO BOX 56
University of Otago
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 312090 0
None
Name [1] 312090 0
Address [1] 312090 0
Country [1] 312090 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310401 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 310401 0
Ethics committee country [1] 310401 0
New Zealand
Date submitted for ethics approval [1] 310401 0
Approval date [1] 310401 0
11/02/2022
Ethics approval number [1] 310401 0
2021 FULL 11864

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117530 0
Dr Divya Adhia
Address 117530 0
201 Great King Street, Dunedin hospital, 6th floor, Room 607,
Department of Surgical Sciences, Otago Medical School, University of Otago.
Dunedin
9013
New Zealand
Country 117530 0
New Zealand
Phone 117530 0
+64 211167594
Fax 117530 0
Email 117530 0
[email protected]
Contact person for public queries
Name 117531 0
Divya Adhia
Address 117531 0
201 Great King Street, Dunedin hospital, 6th floor, Room 607,
Department of Surgical Sciences, Otago Medical School, University of Otago.
Dunedin
9013
New Zealand
Country 117531 0
New Zealand
Phone 117531 0
+64 211167594
Fax 117531 0
Email 117531 0
[email protected]
Contact person for scientific queries
Name 117532 0
Divya Adhia
Address 117532 0
201 Great King Street, Dunedin hospital, 6th floor, Room 607,
Department of Surgical Sciences, Otago Medical School, University of Otago.
Dunedin
9013
New Zealand
Country 117532 0
New Zealand
Phone 117532 0
+64 211167594
Fax 117532 0
Email 117532 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.