Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000415909
Ethics application status
Approved
Date submitted
12/03/2020
Date registered
27/03/2020
Date last updated
27/03/2020
Date data sharing statement initially provided
27/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Testing brain stimulation for improving memory and function in early Alzheimer’s disease.
Scientific title
Effect of high definition transcranial infraslow pink noise stimulation on cognition and function in individuals with early Alzheimer’s disease: A pilot double-blind randomised controlled study.
Secondary ID [1] 300777 0
None
Universal Trial Number (UTN)
U1111-1244-5636
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Alzheimer's Disease 316626 0
Condition category
Condition code
Neurological 314864 314864 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial electrical stimulation will be administered three times a week (30 minutes/ session) for a total of 8 weeks (i.e. 24 sessions in total) using a 32 channel transcranial current stimulator (Starstim32 TES®, Neuroelectrics, Spain), by a researcher with health professional background and considerable experience in administering non-invasive neuromodulation techniques. The participants will be positioned comfortably and quietly in a seated/half lying position on a bed, and will wear a neoprene head cap with circular stimulation electrodes placed on it. For the active treatment group, the stimulation will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. For sham stimulation, to create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.
Intervention code [1] 317102 0
Treatment: Devices
Comparator / control treatment
Sham stimulation: To create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.
Control group
Placebo

Outcomes
Primary outcome [1] 323203 0
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 [1] 323203 0
During each intervention sessions (at intervals of 5 minutes), and immediately post-intervention phase.
Primary outcome [2] 323204 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.
Timepoint [2] 323204 0
Throughout the intervention period
Primary outcome [3] 323205 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] 323205 0
Baseline and Immediately post-intervention
Secondary outcome [1] 381173 0
Alzheimer's Disease Functional Assessment and Change Scale
Timepoint [1] 381173 0
Baseline and Immediately post-intervention
Secondary outcome [2] 381174 0
European Quality of Life–5 Dimensions
Timepoint [2] 381174 0
Baseline and Immediately post-intervention
Secondary outcome [3] 381175 0
Memory Assessment Clinics- family
Timepoint [3] 381175 0
Baseline and Immediately post-intervention
Secondary outcome [4] 381176 0
World Health Organisation- Five Well-Being Index
Timepoint [4] 381176 0
Baseline and Immediately post-intervention
Secondary outcome [5] 381177 0
State-Trait Anxiety Inventory
Timepoint [5] 381177 0
Baseline and Immediately post-intervention
Secondary outcome [6] 381178 0
Intolerance of Uncertainty Scale - Short Form
Timepoint [6] 381178 0
Baseline and Immediately post-intervention
Secondary outcome [7] 381179 0
Medical Outcomes Study-Sleep Scale
Timepoint [7] 381179 0
Baseline and Immediately post-intervention

Eligibility
Key inclusion criteria
• Capable of understanding and signing an informed consent form
• A diagnosis of ‘probable’ or ‘possible’ Alzheimer’s disease based on National Institute on Aging and Alzheimer’s Association (NIA-AA) guidelines
• A score of 0.5 in the Clinical Dementia Rating scale
• A score of 60 points or higher on the Cambridge Cognitive Examination (CAMCOG-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
• 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)
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)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive statistics will be used to analyse feasibility and safety measures. Linear mixed model regression analysis will be used to obtain estimates of the intervention effects on cognitive, functional, and quality of life outcome measures.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/05/2020
Actual
Date of last participant enrolment
Anticipated
29/10/2021
Actual
Date of last data collection
Anticipated
24/12/2021
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 22436 0
New Zealand
State/province [1] 22436 0
Otago

Funding & Sponsors
Funding source category [1] 305237 0
University
Name [1] 305237 0
University of Otago Research Grant
Country [1] 305237 0
New Zealand
Primary sponsor type
Individual
Name
Dr Divya Adhia
Address
PO BOX 56
University of Otago
Department of Surgical Sciences,
Dunedin School of Medicine.
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 305593 0
None
Name [1] 305593 0
Address [1] 305593 0
Country [1] 305593 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305580 0
Southern Health and Disability Ethics Committe
Ethics committee address [1] 305580 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 305580 0
New Zealand
Date submitted for ethics approval [1] 305580 0
Approval date [1] 305580 0
10/03/2020
Ethics approval number [1] 305580 0

Summary
Brief summary
The purpose of this study is to evaluate the safety and to explore the effect of a non-invasive external brain stimulation technique [Transcranial electrical stimulation (TES)] on cognition (e.g. memory, attention), function, and quality of life in individuals with early Alzheimer's disease. The activity in the brain region [posterior cingulate cortex
(PCC)] targeted in the current study have been demonstrated to be altered in the very early stages of AD and are associated with cognitive dysfunctions. The TES technique has considerable potential as a treatment for AD due to its relatively low cost, safety, portability, and ease of use compared with other brain stimulation methods. We propose to explore a novel TES technique [high definition transcranial infraslow pink noise stimulation (HD-tIPNS)] targeting the PCC. The HD-tIPNS technique has been specifically developed in our Otago Brai3n laboratory to modulate the infraslow electrical activity (0.01-0.1 Hz) in the brain. The infraslow electrical activity, a fundamental frequency range of the brain, re-organises neurons, regulate oscillatory patterns in the brain during awake and
sleep cycles, and improves the electrical connectivity of the brain-wide functional networks; thereby improve cognitive functioning. The evidence obtained from this study will thus help us to develop novel interventions to improve the health outcomes (cognition and function) in individuals with early AD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100846 0
Dr Divya Adhia
Address 100846 0
Department of Surgical Science,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 100846 0
New Zealand
Phone 100846 0
+64 211167594
Fax 100846 0
Email 100846 0
[email protected]
Contact person for public queries
Name 100847 0
Dr Divya Adhia
Address 100847 0
Department of Surgical Science,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 100847 0
New Zealand
Phone 100847 0
+64 211167594
Fax 100847 0
Email 100847 0
[email protected]
Contact person for scientific queries
Name 100848 0
Dr Divya Adhia
Address 100848 0
Department of Surgical Science,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 100848 0
New Zealand
Phone 100848 0
+64 211167594
Fax 100848 0
Email 100848 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.