Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000297628
Ethics application status
Approved
Date submitted
8/03/2023
Date registered
17/03/2023
Date last updated
29/02/2024
Date data sharing statement initially provided
17/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the potential of pupil-dilating and pupil-constricting eye drops as a treatment for presbyopia
Scientific title
Investigating the role of mainstream Pharmacological agents in the Regulation of the Optical Properties of the in vivo human ocular Lens (PROPeL) study
Secondary ID [1] 309145 0
Nil known
Universal Trial Number (UTN)
Nil known
Trial acronym
PROPeL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Presbyopia 329247 0
Condition category
Condition code
Eye 326205 326205 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eye drops that relax the ciliary muscle (i.e. pupil-dilating eye drops) will be instilled in young participants (those aged between 18 and 40 years old). These include: Tropicamide 10 mg/mL (1%) and/or Cyclopentolate hydrochloride 10 mg/mL (1%). Eye drops that contract the ciliary muscle (i.e. pupil-constricting eye drops) will be instilled in participants with presbyopia (those aged over 40 years old). These include: Pilocarpine hydrochloride 10 mg/mL (1%) or 12.5 mg/mL (1.25%).
The ability of the ciliary muscle to contract or relax is dependent on age, hence instillation of different eye drops to induce different ciliary muscle behaviour in young vs. middle-aged participants is required. Amongst the eye drops listed for each age group, which one a participant receives is personalised according to how pigmented their iris is, as iris pigmentation is a factor that influences the time to onset, duration of action, and recovery period of these eye drops. Grading of iris pigmentation and subsequent allocation of eye drops will be done by an NZ-registered optometrist who is a named study investigator at the initial study visit. Participants will have 1 drop of their allocated eye drops administered into each eye at two out of three study visits by an NZ-registered optometrist who is a named study investigator.
The first study visit involves an optometric examination and will be between 1 and 1.5 hours long. It includes a general assessment of vision and eye health, baseline measurements of study parameters, instillation of eye drops, and then repeat measurement of study parameters 30-60 min after eye drop administration.
The second and third study visits involve an MRI scan to obtain measures of study parameters. The first MRI scan (i.e. the second study visit) will be to obtain baseline measurements. The second MRI scan (i.e. the third study visit) will be performed 30-60 min after eye drop instillation to remeasure the same study parameters. Each MRI scan will take approximately 30-45 mins.
All study visits will be conducted on separate days but with no specific time interval between visits required. However, all 3 visits must be completed within 6 to 8 weeks of the first study visit.
Intervention code [1] 325594 0
Prevention
Intervention code [2] 325636 0
Treatment: Drugs
Comparator / control treatment
Participants serve as their own control. We will conduct a comparison of outcome measures between without and with instillation of eye drops.
Control group
Active

Outcomes
Primary outcome [1] 334081 0
Change in the lens gradient of refractive index (GRIN), obtained with magnetic resonance imaging (MRI). The lens GRIN can be characterised by the following parameters: the magnitude of the central lens refractive index, the magnitude of the peripheral lens refractive index, and the shape exponent describing the rate of refractive index variation going from the lens centre to the periphery.
Timepoint [1] 334081 0
1 hr after instillation of eye drops
Primary outcome [2] 334082 0
Change in the lens water distribution, measured by magnetic resonance imaging (MRI). The lens water distribution can be characterised by the following parameters: the amount of water at the lens centre, the amount of water at the peripheral lens, and the shape exponent describing the rate of water variation going from the lens centre to the periphery.
Timepoint [2] 334082 0
1 hr after instillation of eye drops
Primary outcome [3] 334083 0
Change in the geometric and volumetric parameters of the lens, measured by magnetic resonance imaging (MRI). These include: the axial lens thickness, lens equatorial diameter, anterior and posterior lens surface radii of curvature, lens cross-sectional area, lens surface area and lens volume. These parameters will be analysed together as a composite primary outcome.
Timepoint [3] 334083 0
1 hr after instillation of eye drops
Secondary outcome [1] 419306 0
Change in the lens refractive properties, namely the optical power and spherical aberration, calculated by optical modelling. The optical models used to calculate these outputs will be constructed using the various parameters obtained from MRI scans of the lens in combination with measures of vision performance obtained clinically.
Timepoint [1] 419306 0
1 hr after instillation of eye drops
Secondary outcome [2] 419471 0
Change in vision performance at the level of the whole eye, such as distance and near visual acuity and refraction, amplitude of accommodation and depth-of-focus. These will be measured using standard optometric tests by a NZ-registered optometrist. Distance (6 m) and near (40 cm) visual acuity will be measured using a logMAR eye chart under photopic (~251 lux) lighting conditions. Distance and near refraction will be measured using noncycloplegic subjective refraction in photopic lighting. Amplitude of accommodation will be measured objectively using the minus lens to blur method in conjunction with autorefraction. Depth-of-focus will be measured in photopic lighting using a phoropter as well as by obtaining pupil diameter measurements with a pupillometer. Lenstar optical biometer will also be used to obtain ocular biometry parameters that will be used to construct the optical models.
Timepoint [2] 419471 0
1 hr after instillation of eye drops

Eligibility
Key inclusion criteria
Healthy adults who are willing and able to provide written informed consent for study participation.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Significant refractive error, defined as over 6 Dioptres of myopic or hyperopic mean sphere refractive error
- History of ocular pathology or intraocular surgery that has the potential to affect the participant’s vision at the time of study participation
- A personal or family history of epilepsy or seizures, neurological disorders/ disease, or serious head injury and/or skull fracture, as these may affect performance in MRI procedures involving viewing flickering visual patterns (e.g. epilepsy) and/or lying still for an extended period of time (e.g. claustrophobia)
- Having metal implants (e.g. a cardiac pacemaker) or other contraindications that would put the safety of the participant at risk when undergoing an MRI scan
- Pregnant or breastfeeding women, as safety of the eye drops used in this study has not been established for use in pregnancy and lactation. For this reason, participants who become pregnant during the study will also not be able to continue participation.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
GraphPad Prism (GraphPad Software, San Diego, CA) and/or SPSS Statistics (IBM, Armonk, NY) will be used for conducting statistical analyses. All statistical tests will be two-tailed and at 5% significance level throughout the analyses. Summaries of continuous variables which are normally distributed will be presented as means and standard deviations or medians and inter-quartiles for skewed data, while categorical variables will be presented as frequencies and percentages. Paired t-test will be used to test for differences in endpoint measures without and with the instillation of eye drops. The assumption of normality of data will be assessed by visual inspection of Normal Q-Q plots and/or Shapiro-Wilk test of normality. Upon violation of the assumption of normality, a nonparametric Wilcoxon signed-rank test will be conducted instead of a paired t-test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/03/2023
Actual
13/06/2023
Date of last participant enrolment
Anticipated
4/03/2024
Actual
30/09/2023
Date of last data collection
Anticipated
1/04/2024
Actual
3/11/2023
Sample size
Target
20
Accrual to date
Final
19
Recruitment outside Australia
Country [1] 25311 0
New Zealand
State/province [1] 25311 0
Auckland

Funding & Sponsors
Funding source category [1] 313346 0
Government body
Name [1] 313346 0
National Institute of Health
Country [1] 313346 0
United States of America
Funding source category [2] 313348 0
University
Name [2] 313348 0
The University of Auckland
Country [2] 313348 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 90210
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 315094 0
None
Name [1] 315094 0
Address [1] 315094 0
Country [1] 315094 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312568 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 312568 0
Ethics committee country [1] 312568 0
New Zealand
Date submitted for ethics approval [1] 312568 0
10/10/2022
Approval date [1] 312568 0
31/01/2023
Ethics approval number [1] 312568 0
2023 EXP 13538

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

Contacts
Principal investigator
Name 125122 0
Dr Alyssa Lie
Address 125122 0
School of Optometry and Vision Science
The University of Auckland
85 Park Road, Grafton
Auckland 1023
Country 125122 0
New Zealand
Phone 125122 0
+64 21 0266 4662
Fax 125122 0
Email 125122 0
[email protected]
Contact person for public queries
Name 125123 0
Alyssa Lie
Address 125123 0
School of Optometry and Vision Science
The University of Auckland
85 Park Road, Grafton
Auckland 1023
Country 125123 0
New Zealand
Phone 125123 0
+64 9 923 6483
Fax 125123 0
Email 125123 0
[email protected]
Contact person for scientific queries
Name 125124 0
Alyssa Lie
Address 125124 0
School of Optometry and Vision Science
The University of Auckland
85 Park Road, Grafton
Auckland 1023
Country 125124 0
New Zealand
Phone 125124 0
+64 21 0266 4662
Fax 125124 0
Email 125124 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
There is no provision for sharing IPD in the ethical approval and therefore no provision for obtaining informed consent from participants to share IPD on the participant information sheet and consent form.


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.