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Trial registered on ANZCTR


Registration number
ACTRN12621001187831
Ethics application status
Approved
Date submitted
5/11/2020
Date registered
3/09/2021
Date last updated
3/09/2021
Date data sharing statement initially provided
3/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical utility of Quantum Molecular Resonance treatment for dry eye disease
Scientific title
Clinical utility of Quantum Molecular Resonance treatment for dry eye disease
Secondary ID [1] 302715 0
None
Universal Trial Number (UTN)
U1111-1260-5951
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Meibomian gland dysfunction 319630 0
Aqueous deficiency dry eye 319631 0
Evaporative dry eye 319632 0
Condition category
Condition code
Eye 317571 317571 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Rexon-Eye (Telea Electronic Engineering, Italy) is a commercially available device that generates Quantum Molecular Resonance (QMR) by high-frequency (4–64 MHz) and low-power (60–120 mJ/cm2/s) electrical currents. Each session of stimulation consists of electrodes being placed in the periorbital area of both eyes via a ‘goggle like’ device. Its proposed mechanism of action is based on the resonance effect, which is the delivery of energy to biological tissues by oscillating electric fields without significantly increasing the temperature, and eliciting biological responses to achieve both pathophysiological and potentially therapeutic benefits.

In this prospective, double-masked, placebo-controlled trial, participants will receive either 4 x weekly Rexon-Eye treatments or 4 weekly sham treatments (with heat to mimic QMR application, but omitting the application of the low power, high frequency stimulation), over the course of one month. Treatment will be applied by a trained individual uninvolved in collecting study outcomes. Three ‘follow-up’ visits are arranged at 1 month, 2 months, and 3 months after the fourth treatment session, to measure clinical outcomes only.
Intervention code [1] 318993 0
Treatment: Devices
Comparator / control treatment
Goggles which appear similar to the intervention (with low heat to mimic QMR application, but omitting the application of the low power, high frequency stimulation).
Control group
Placebo

Outcomes
Primary outcome [1] 325613 0
Change in non-invasive tear breakup time (NIBUT) as measured by the Oculus Keratograph 5M.
Timepoint [1] 325613 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed weekly over a month period).

Primary timepoint is the 3 month follow-up visit.
Secondary outcome [1] 388566 0
Change in lipid layer thickness as graded from interference patterns observed on imaging by the Oculus Keratograph 5M.
Timepoint [1] 388566 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed one week apart, over a one month period).

Secondary timepoint is the 3 month follow-up visit.
Secondary outcome [2] 388567 0
Change in tear meniscus (tear fluid adjacent to the lower eyelid) will be digitally analysed to determine the exact tear meniscus height by the Oculus Keratograph 5M.
Timepoint [2] 388567 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed one week apart, over a one month period).

Secondary timepoint is the 3 month follow-up visit.
Secondary outcome [3] 388568 0
Change in Symptom Assessment in Dry Eye (SANDE) questionnaire score, which comprises of two questions that use a 100 mm horizontal linear visual analogue scale to quantify both severity and frequency of dry eye symptoms.
Timepoint [3] 388568 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed one week apart, over a one month period).

Secondary timepoint is the 3 month follow-up visit.
Secondary outcome [4] 388569 0
Change in Ocular Surface Disease Index (OSDI) questionnaire score.
Timepoint [4] 388569 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed one week apart, over a one month period).

Secondary timepoint is the 3 month follow-up visit.
Secondary outcome [5] 388570 0
Evaluation of meibomian gland expressibility with slit lamp biomicroscopy and a diagnostic expression instrument (Korb Meibomian Gland Evaluator).
Timepoint [5] 388570 0
Measurements will be recorded at baseline, then on 1 month, 2 month, and 3 month follow-up visits after the conclusion of the intervention treatment course (4 treatments performed one week apart, over a one month period).

Secondary timepoint is the 3 month follow-up visit.

Eligibility
Key inclusion criteria
Participants with symptomatic dry eye caused by evaporative causes (e.g. meibomian gland dysfunction) or aqueous deficient causes (e.g. Sjögren's syndrome).

Participants will be required to:
• Meet TFOS DEWS II criteria for dry eye diagnosis
• Be willing and able to follow the protocol accurately
• Be willing to minimise application of dry eye treatments beyond the study treatment

TFOS DEWS II dry eye diagnosis:
Adult participants meeting the criteria for dry eye disease according to the TFOS DEWS II diagnostic criteria (symptoms: OSDI greater or equal to 13, DEQ-5 greater or equal to 6; plus one or more signs: non-invasive breakup time (NIBUT) less than 10s, osmolarity greater than 308 or interocular diff of greater or equal to 8; greater than 5 spots corneal staining with NaFl, greater than 9 spots conjunctival staining with lissamine green, lid margin staining (lid wiper epitheliopathy) of greater or equal to 2mm in length and greater or equal to 25% lid margin width will be recruited.

Subclassification according to dry eye status (ADDE, EDE or mixed) and severity (mild-moderate vs moderate-severe) will be determined according to established cut-offs.

For EDE: Clinically significant signs of MGD: (eyelid margin or mucocutaneous junction abnormalities, meibomian gland orifice capping, and/or decreased expressed meibum quality).

For ADDE: reduced tear meniscus height (less than 0.2mm).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
• OPAS score greater than 70% on questions 1, 4 or 7 indicating possible ocular neuropathic pain that may be unresponsive to treatment
• Contact lens wear, or application of topical therapies other than dry eye drops within two weeks of the eligibility assessment or during the trial
• Use of systemic medications known to affect the ocular surface or tear production
• Current or planned pregnancy or lactation during the study
• History of major systemic, dermatologic or ocular conditions
• Ocular surgery or dermatologic treatments in the previous three months or planned during the treatment period.
• Unwillingness to refrain from dye drop application on study visit days
• Use of warm compresses or lid hygiene unless applied regularly as part of a stable regime for greater than 3 months and continued throughout trial, but not within 24 hours of study visits
• LipiFlow, IPL (Intense Pulsed Light) or investigational treatment for dry eye disease within 6 months of study start
• Lid debridement or therapeutic meibomian gland expression within 1 month of study start

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)
This study is a randomised, double-masked, placebo-controlled clinical trial. The interventional treatment (QMR or placebo) will be applied by a second, independent researcher. Allocation to treatment (active or sham) will be derived by computer-generated random number allocation and applied to sequentially enrolled participants at each site. The randomisation schedule will be pre-determined prior to patient recruitment, such that the investigator involved in baseline participant assessment will have no influence in treatment allocation.
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
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size:
Non-parametric adjusted power calculations were conducted using NCSS PASS 2002 (Utah, USA), with non-invasive tear film break-up time as the designated outcome, and showed that a minimum of 29 participants per group was required, to detect a clinically significant difference of 4 seconds in pairwise comparisons, with 80% power (ß equal 0.2) at a two-sided statistical significance, and the SD estimated to be 5 seconds.

Statistical analysis:
Data will be analysed statistically to evaluate treatment and time effects, using parametric and non-parametric tests as appropriate, for normally and non-normally distributed data, respectively.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2021
Actual
Date of last participant enrolment
Anticipated
1/01/2022
Actual
Date of last data collection
Anticipated
1/04/2022
Actual
Sample size
Target
58
Accrual to date
Final
Recruitment outside Australia
Country [1] 23093 0
New Zealand
State/province [1] 23093 0
Auckland

Funding & Sponsors
Funding source category [1] 307145 0
Commercial sector/Industry
Name [1] 307145 0
Resono Ophthalmic
Country [1] 307145 0
Italy
Primary sponsor type
University
Name
The University of Auckland
Address
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 307729 0
None
Name [1] 307729 0
Address [1] 307729 0
Country [1] 307729 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307258 0
The Auckland Health Research Ethics Committee (AHREC)
Ethics committee address [1] 307258 0
Ethics committee country [1] 307258 0
New Zealand
Date submitted for ethics approval [1] 307258 0
21/06/2021
Approval date [1] 307258 0
26/07/2021
Ethics approval number [1] 307258 0
AH22938

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

Contacts
Principal investigator
Name 106594 0
Prof Jennifer P. Craig
Address 106594 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 106594 0
New Zealand
Phone 106594 0
+64 09 923 8173
Fax 106594 0
Email 106594 0
jp.craig@auckland.ac.nz
Contact person for public queries
Name 106595 0
Jennifer P. Craig
Address 106595 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 106595 0
New Zealand
Phone 106595 0
+64 09 923 8173
Fax 106595 0
Email 106595 0
jp.craig@auckland.ac.nz
Contact person for scientific queries
Name 106596 0
Jennifer P. Craig
Address 106596 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 106596 0
New Zealand
Phone 106596 0
+64 09 923 8173
Fax 106596 0
Email 106596 0
jp.craig@auckland.ac.nz

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.