Oral glycoside supplement (triterpenoid saponins) for early and intermediate stage age-related macular degeneration (SAMADI trial): study protocol for a double masked randomised placebo-controlled feasibility trial

Abstract Background The primary aim of the SAMADI [SAponins for MAcular DIsease] trial is to establish whether treatment of age-related macular degeneration (AMD) with oral saponin supplements is feasible and acceptable to participants. AMD is a progressive disease, which results in the death and dysfunction of cells in the outer retina. One potential contributor to AMD progression is the reduced permeability of Bruch’s membrane underlying the retina. Saponins have a structure enabling them to assist dispersal of lipid deposits in Bruch’s membrane, providing a rationale for the proposed intervention in AMD. Secondary aims are to provide an estimate of the variability of a proposed future primary outcome, and to provide estimates of treatment effects of clinical outcomes. Methods SAMADI is a double masked randomised feasibility trial, which will recruit 60 participants with early or intermediate AMD in at least one eye. Participants will be randomly assigned into one of two groups, one receiving the oral saponin tablets and the other placebo tablets (indistinguishable in appearance), both to be taken daily for 4 months. Participants and research optometrists will be masked to the allocation. Clinical tests will be repeated at baseline, 4 months and 12 months. The primary outcome measures relate to feasibility of the following aspects of the intervention and study design: (1) recruitment and retention over 4 and 12 months; (2) adherence to treatment and acceptability of intervention; (3) the eligibility assessment process; (4) collecting the outcome data. The rate of serious adverse events will be an additional primary outcome measure. Secondary outcomes include dark adaptation metrics, best corrected visual acuity, contrast sensitivity, fundus imaging, low luminance questionnaire, standard electroretinograms according to International Society for Clinical Electrophysiology of Vision standard protocols, and imaging retinal densitometry (at one site only). Discussion The data will be used to determine the feasibility of the trial design, how well participants complied with taking the tablets, and the potential effectiveness of the treatment. If feasible, this information will be used to inform a larger trial, which will definitively assess how effective the treatment is in participants with AMD. Trial registration The trial is registered with EudraCT and ISRCTN registries. EudraCT ref: 2021–003045-38; Date of registration: 24/05/2021. ISRCTN ref: ISRCTN82949875; Date of registration: July 21, 2021. URL: https://www.isrctn.com/ISRCTN82949875 . Version and date: This report is based on Protocol V3, January 2024. Sponsor: Cardiff University, Research Governance Team, Research and Innovation Services, Cardiff University, 7th Floor, McKenzie House, 30–36 Newport Road, Cardiff CF24 0DE.