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Trial registered on ANZCTR
Registration number
ACTRN12617000034336
Ethics application status
Approved
Date submitted
3/01/2017
Date registered
9/01/2017
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Date results information initially provided
29/01/2019
Type of registration
Prospectively registered
Titles & IDs
Public title
An investigation into the effect of skin stimulation on smell function
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Scientific title
An investigation for the modulation of Olfactory (Smell) function using Non-Invasive Transcutaneous Electrical Nerve Stimulation in healthy adult male volunteers
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Secondary ID [1]
290830
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None
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Universal Trial Number (UTN)
U1111-1191-3010
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Trial acronym
MODOLF
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alzheimer disease
301504
0
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Parkinson's Disease
301535
0
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Dementia
301536
0
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Appetite disorders
301537
0
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Condition category
Condition code
Neurological
301214
301214
0
0
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Alzheimer's disease
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Neurological
301255
301255
0
0
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Parkinson's disease
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Neurological
301256
301256
0
0
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Dementias
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Transcutaneous Electrical Nerve Stimulation (TENS) will be applied under the pain threshold with CE approved home use TENS device by a researcher who is a medical doctor.
Different dilutions of smell sticks (scientifically validated and medically approved) will be used to determine the smell function of the participants before and after the TENS interventions by an odour researcher. The number of the smell sticks that will be used may differ 4 to 10 because of the interindividual smell threshold differences.
In all sessions, frontal cortex activation will be monitored for olfactory function responses with FDA approved near infrared monitoring device (NIRS). In each arm, there will be two streams: low(10Hz) and high frequency(80Hz) stimulation. 24 participants of each Arm will be allocated into two streams: 12 participants for low frequency stimulation stream and the other 12 participants for high frequency stimulation stream. Each stream will also have their own placebo group in which the same 12 participants will be enrolled. There is no evidence that 10 minutes of a single stimulation have prolonged effects. In addition, each session will be performed on a different day(active or placebo) so that the participants will be participating in different days for each session to eliminate the possible overlapping effects of the previous session. Each session duration will take 1 hour (baseline tests+stimulation+after stimulation tests) and each participant will be participating for a total of 2 hours in two different days(one day for active and one day for placebo session). All sessions will take place in the live human research/ultrasound room in Otago University, Department of Anatomy, Dunedin.
Arm1 : TENS will be applied to ear skin(direct vagus nerve stimulation) with ear specific TENS electrode under pain threshold to 24 healthy volunteers for 10 minutes. This is a within designed study, therefore each participant will be participating both to an active and a placebo. 12 of the participants will be allocated to low frequency active stimulation stream and the other 12 of the participants will be allocated to high frequency active stimulation stream.Each stream will also have their own placebo group in which the same 12 participants will be enrolled.
Arm2: TENS will be applied to wrist skin(indirect vagus nerve stimulation) with body specific TENS electrode under pain threshold to 24 healthy volunteers for 10 minutes. This is a within designed study, therefore each participant will be participating both to active and placebo groups. 12 of the participants will be allocated to low frequency active stimulation stream and the other 12 of the participants will be allocated to high frequency active stimulation stream. Each stream will also have their own placebo group in which the same 12 participants will be enrolled.
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Intervention code [1]
296751
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Treatment: Devices
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Comparator / control treatment
This is a within study on healthy volunteers. Each participant will be enrolled to both active and placebo control groups. In the placebo control group, the TENS electrodes will be placed on the same skin areas for 10 minutes as in the active group but there won't be an electrostimulation.
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Control group
Placebo
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Outcomes
Primary outcome [1]
300627
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Change in Sniff-stick threshold test results (statistical difference in detection odours based on detection of the same odour after the electrostimulation).
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Assessment method [1]
300627
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Timepoint [1]
300627
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before and after 10 minutes of Transcutaneous Electrical Nerve Stimulation or 10 minutes of Placebo session
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Secondary outcome [1]
330438
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% Change in Near Infrared Monitoring score of Frontal Cortex perfusion
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Assessment method [1]
330438
0
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Timepoint [1]
330438
0
before and after 10 minutes of Transcutaneous Electrical Nerve Stimulation or 10 minutes of Placebo session
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Eligibility
Key inclusion criteria
* 22-39 years old male
* NZ European
* In good health, and not on any regular medication
* A non-smoker
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Minimum age
20
Years
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Maximum age
39
Years
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Sex
Males
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
Have a history of allergies, any neurological disorder, cardiac disease or are on regular medication
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
numbered containers
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
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Intervention assignment
Crossover
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Other design features
Within design (same participants will be enrolled both active and placebo groups).
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Phase
Phase 1
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
There was no similar(non-invasive olfactory neuromodulation) study in humans. Therefore the minimum number of participants(n=48) was estimated on the basis of other non-invasive nerve stimulation study designs in humans. In addition, within design is preferred to improve the potential power of the study. T-test will be used to analyze the results.
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
1/02/2017
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Actual
7/02/2017
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Date of last participant enrolment
Anticipated
1/03/2018
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Actual
28/02/2018
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Date of last data collection
Anticipated
2/03/2018
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Actual
28/02/2018
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Sample size
Target
48
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Accrual to date
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Final
40
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Recruitment outside Australia
Country [1]
8540
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New Zealand
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State/province [1]
8540
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OTAGO
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Funding & Sponsors
Funding source category [1]
295254
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University
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Name [1]
295254
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Otago University
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Address [1]
295254
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Department of Anatomy
Otago School of Medical Sciences
University of Otago
PO bOX 913, Dunedin 9054
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Country [1]
295254
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New Zealand
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Primary sponsor type
Individual
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Name
Yusuf Ozgur Cakmak
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Address
Department of Anatomy
Otago School of Medical Sciences
University of Otago
PO bOX 913, Dunedin 9054
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Country
New Zealand
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Secondary sponsor category [1]
294082
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University
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Name [1]
294082
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Otago University
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Address [1]
294082
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Department of Anatomy
Otago School of Medical Sciences
University of Otago
PO bOX 913, Dunedin 9054
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Country [1]
294082
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New Zealand
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
296592
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University of Otago, Human Ethics Committee(Health)
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Ethics committee address [1]
296592
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Room G22 Clocktower Building
University of Otago, Dunedin 9054
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Ethics committee country [1]
296592
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New Zealand
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Date submitted for ethics approval [1]
296592
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09/12/2016
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Approval date [1]
296592
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12/12/2016
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Ethics approval number [1]
296592
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H16/148
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Summary
Brief summary
It has been shown that at the olfactory bulb, where smell is processed, neurons show pathological changes at (smell) olfaction-related neuronal system. Alzheimer disease(AD) and Parkinson's disease(PD) patients show a significant loss of olfactory performance. In sum, the functional regression of the smell function contributes to numerous neurological diseases and therefore, regaining the olfactory function is crucially important for a potential treatment for AD, PD, Dementia and appetite disorders.
Hypothesis: Vagal nerve fibers convey the visceral information to the olfactory bulb. Invasive Vagal Nerve Stimulation (VNS), using surgery, has been shown to decrease thresholds of the olfactory bulb neurons. This is directly associated with a lower detection threshold for the smell. It is also reported that invasive VNS increases the glucose uptake in the olfactory bulb. In a human study using invasive VNS, devices were implanted at vagal nerve sites in the neck region. Olfactory information processing was influenced and modulated with neck-implanted VNS devices. Results affirm the postulation that there is a strong correlation between VNS and olfactory bulb activity.
To date, Olfactory bulb activity modulation with VNS stimulation has only been achieved using invasive VNS techniques. If VNS stimulation could be achieved using a non-invasive technique, this has the potential to be a safe and effective treatment to improve olfactory bulb function for AD, PD Dementia and Appetite disorder patients. To date, there has been no study on the non-invasive VNS effects on olfactory function. In the present trial, we will investigate the efficacy of the non-invasive VNS (pain-free, electrical stimulation of the skin) on altering the olfactory function in healthy humans. Data collection and subsequent assessment will (i) achieve clarification of the efficacy of non-invasive direct and indirect VNS to modulate olfactory function, and (ii) distinguish the two distinct frequency effects on modulation of the olfactory threshold, olfactory discrimination and olfactory memory functions in humans.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
71414
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Dr Yusuf Ozgur Cakmak
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Address
71414
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Department of Anatomy
School of Biomedical Sciences
University of Otago
PO BOX 913, DUNEDIN 9054
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Country
71414
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New Zealand
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Phone
71414
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+64-03-479-4030
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Fax
71414
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Email
71414
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[email protected]
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Contact person for public queries
Name
71415
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Dr Yusuf Ozgur Cakmak
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Address
71415
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Department of Anatomy
School of Biomedical Sciences
University of Otago
PO BOX 913, DUNEDIN 9054
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Country
71415
0
New Zealand
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Phone
71415
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+64 3 479 4030
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Fax
71415
0
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Email
71415
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[email protected]
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Contact person for scientific queries
Name
71416
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Dr Yusuf Ozgur Cakmak
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Address
71416
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Department of Anatomy
School of Biomedical Sciences
University of Otago
PO BOX 913, DUNEDIN 9054
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Country
71416
0
New Zealand
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Phone
71416
0
+64 3 479 4030
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Fax
71416
0
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Email
71416
0
[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
We published the results and the method/data/results/outcome is open access.
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
Type
Is Peer Reviewed?
DOI
Citations or Other Details
Attachment
Study results article
Yes
https://www.frontiersin.org/articles/10.3389/fnins...
[
More Details
]
372089-(Uploaded-28-01-2019-13-13-06)-Journal results publication.pdf
Study results article
Yes
https://www.frontiersin.org/articles/10.3389/fnhum...
[
More Details
]
372089-(Uploaded-28-01-2019-13-14-01)-Journal results publication.pdf
Plain language summary
No
In non-invasive vagal nerve stimulation, ear skin ...
[
More Details
]
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
Improvement of olfactory function with high frequency non-invasive auricular electrostimulation in healthy humans.
2018
https://dx.doi.org/10.3389/fnins.2018.00225
Dimensions AI
Non-invasive High Frequency Median Nerve Stimulation Effectively Suppresses Olfactory Intensity Perception in Healthy Males
2019
https://doi.org/10.3389/fnhum.2018.00533
N.B. These documents automatically identified may not have been verified by the study sponsor.
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