Saponins for macular disease

Approved 21/03/2024, Health and Social Care Research Ethics Committee A (HSC REC A) (Office for Research Ethics Committee Northern Ireland (ORECNI), Lissue Industrial Estate West, 5 Rathdown Walk, Lisburn, BT28 2RF, United Kingdom; +44 (0)28 95 361400; reca@hscni.net), ref: 23/NI/0060

The feasibility of a subsequent fully powered trial, assessed using:
1. Recruitment: the proportion of those contacted who are randomised will be tabulated to give an idea of the feasibility of recruitment into a trial in this population
2. Retention: to assess retention over 4 and 12 months. Participants will be contacted by the researchers monthly during the 4-month treatment period. Participants will be sent reminders prior to their 4- and 12-month appointments. The proportion of those randomised who provide complete follow-up clinical data at each timepoint by arm will be tabulated.
3. Adherence to treatment. Participants will be given a tablet diary to complete over the 4-month treatment period (from baseline) and will receive monthly ‘compliance’ phone calls from the researchers to be ‘reminded’ to take their medication. The diary will be returned at 4 months, visit 1. The proportion of participants who adhered to the treatment regimen will be tabulated. The proportion of tablets taken per patient will also be tabulated by arm, assessed from tablet counts.
4. Acceptability of the intervention: an end-of-trial participant questionnaire at 12 months, visit 1, to assess the acceptability of the IMP and trial procedures and for participants to be able to speak about their experiences whilst taking part in the trial
5. Feasibility of the eligibility assessment process: the proportion of participants with all required information to determine eligibility from baseline visit 1 to baseline visit 2: the time taken and the percentage of people who the researchers think are eligible, i.e. who complete baseline visit 1, but who are, on the basis of GP feedback, later ruled out from baseline visit 2 and the study
6. Feasibility of collecting the outcome data: levels of data completeness will be tabulated for each follow-up timepoint for each outcome measure with confidence intervals by arm
7. Serious adverse events (SAEs) including comparative rates between arms. The number of SAEs in each arm will be monitored and tabulated during the intervention and throughout follow up

Measured at baseline, 4 and 12 months:
1. Dark adaptation with calculation of cone tau(s), rod cone break time (s) and the slope of the S2 component of the rod dark adaptation function (log cdm-2 per s)
2. Visual acuity measured using a standard Early Treatment Diabetic Retinopathy Study (ETDRS) test in both eyes and binocularly with their distance refractive error in place (number of letters)
3. Contrast sensitivity measured using a Pelli Robson letter chart in both eyes and binocularly with participant’s habitual distance refractive error in place
4. Patient-reported outcome measure (PROM) (Low Luminance Questionnaire) score
5. International Society for Clinical Electrophysiology of Vision (ISCEV) electrophysiology protocol recorded using an Espion E3 Electroretinography System. The standard ISCEV ERG protocol for both eyes includes the following individual tests: dark-adapted 0.01 ERG; dark-adapted 3 ERG; dark-adapted 10 ERG; light-adapted 3.0 ERG; light-adapted 30 Hz flicker ERG. The parameters (amplitudes and implicit times) for each test will be calculated.
6. Beckman AMD clinical grading based on colour fundus photography of the posterior pole from both eyes (45° photographs) and augmented by evaluation of optical coherence tomography macular images (20° x 20°)
7. Retinal and intra-retinal layer thickness derived from automated segmentation of optical coherence tomography macular images (20° x 20°)
8. Near infra-red confocal scanning laser ophthalmoscopy (NIR cSLO) and optical coherence tomography macular images obtained using a Heidelberg Spectralis and colour retinal photography to provide a visual record of ocular/retinal health and assess eligibility