Saponins for macular disease
| ISRCTN | ISRCTN82949875 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82949875 |
| EudraCT/CTIS number | 2021-003045-38 |
| IRAS number | 1004543 |
| Secondary identifying numbers | SPON1833-20, IRAS 1004543, CPMS 58443 |
- Submission date
- 15/04/2023
- Registration date
- 02/04/2024
- Last edited
- 01/10/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Eye Diseases
Plain English summary of protocol
Background and study aims
Photoreceptor cells in the retina of the eye detect light and their death results in blindness. These cells are supported by the delivery of nutrients from the blood, across Bruch’s membrane and the retinal pigment epithelium (RPE), and the removal of toxic waste products in the opposite direction. In the young, Bruch’s membrane is fairly porous allowing an efficient exchange of nutrients and waste products, but with age, there is an accumulation of deposits resulting in a decrease in the ease with which these products are transported. In age-related macular degeneration (AMD), these ageing changes in Bruch’s membrane are advanced, compromising metabolic support to the photoreceptors and leading to blindness. The obvious intervention in the disease would be to remove the deposits and restore the metabolic support to the photoreceptor cells. This study aims to establish whether treatment of AMD with oral saponins or glycoside supplements, which can remove some of the waste products from Bruch's membrane, is feasible and acceptable to participants.
Who can participate?
Patients aged 60-85 years with AMD in both eyes and early or intermediate-stage AMD in at least one eye
What does the study involve?
Participants are randomly allocated to take an oral glycoside supplement (triterpenoid saponins) or matched placebo (dummy) tablets daily after a meal for 4 months. Participants attend the optometry centre for six visits over 12 months.
What are the possible benefits and risks of participating?
There were no adverse effects in any of the many clinical trials with saponins. Rare cases of mild insomnia, diarrhoea, nausea, headache and gastric discomfort have been reported but were only transitory. Some controversy remains as to whether saponins interfere with warfarin anticoagulant treatment. Participants being treated with warfarin (and vitamin K antagonists [phenindione, acenocoumarol]) will be excluded from this trial. Breathing problems, tightness in the throat, chest pain, skin hives, rash or itchy or swollen skin may mean a participant is allergic to sea cucumber products and should stop taking them immediately. Therefore, people with a known or suspected seafood allergy cannot participate.
Where is the study run from?
Cardiff University Optometry Centre and City Sight Optometry Centre, City, University of London (UK)
When is the study starting and how long is it expected to run for?
October 2020 to September 2025
Who is funding the study?
AltRegen Co. Ltd (South Korea)
Who is the main contact?
Prof. Tom Margrain, margrainth@cardiff.ac.uk
Contact information
Scientific
School of Optometry and Vision Sciences
Cardiff University
Maindy Road
Cardiff
CF24 4HQ
United Kingdom
| Phone | +44 (0)29 2087 6118 |
|---|---|
| margrainth@cardiff.ac.uk |
Principal Investigator
School of Optometry and Vision Sciences
Cardiff University
Maindy Road
Cardiff
CF24 4HQ
United Kingdom
| Phone | +44 (0)29 2087 6118 |
|---|---|
| margrainth@cardiff.ac.uk |
Study information
| Study design | Multicentre double-masked individually randomized placebo-controlled feasibility trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | University/medical school/dental school |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet: SAMADI@cardiff.ac.uk |
| Scientific title | Oral glycoside supplement (triterpenoid saponins) for early and intermediate stage age-related macular degeneration: an exploratory randomised placebo-controlled trial |
| Study acronym | SAMADI |
| Study objectives | To establish whether treatment of age-related macular degeneration (AMD) with oral glycoside supplements is feasible and acceptable to participants. |
| Ethics approval(s) |
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 |
| Health condition(s) or problem(s) studied | Men and women with early or intermediate stage age-related macular degeneration (AMD) in the trial eye and any stage of AMD in the non-trial eye |
| Intervention | Randomisation will take place at baseline visit 2 (up to 3 weeks after baseline visit 1) when eligibility has been confirmed. Randomisation will be by blocked randomisation stratified by site and age-related macular degeneration (AMD) severity. Oral glycoside supplement (triterpenoid saponins) versus matched placebo, 4 tablets (117 mg saponins total daily dose) daily, orally, after a meal for 4 months. Follow up 4 months after baseline (after treatment has ended): Month 4, visit 1, followed by Month 4, visit 2 (up to 4 weeks after visit 1). Month 12, visit 1 followed by Month 12 visit 2 (up to 4 weeks after visit 1). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Triterpenoid saponins |
| Primary outcome measure | 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 |
| Secondary outcome measures | 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 |
| Overall study start date | 31/10/2020 |
| Completion date | 30/09/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 60 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | 60 |
| Key inclusion criteria | Current participant inclusion criteria as of 25/07/2024: 1. Aged 60 to 85 years old (inclusive) 2. Able to provide informed consent and comply with the trial visit schedule 3. AMD in both eyes (of any stage) 4. Early or intermediate stage AMD (Beckman classification) in at least one eye Previous participant inclusion criteria: 1. Aged 55 to 85 years old (inclusive) 2. Able to provide informed consent and comply with the trial visit schedule 3. AMD in both eyes (of any stage) 4. Early or intermediate stage AMD (Beckman classification) in at least one eye |
| Key exclusion criteria | Current participant exclusion criteria as of 25/07/2024: 1. Ocular pathology in the study eye (or in either eye for genetic conditions or glaucoma), other than age-related macular degeneration, which may affect visual function 2. Intraocular pressure of 24 mmHg or greater 3. Grade <2 van Herick or history of allergic reaction to dilating eye drops 4. Unable to classify AMD grade 5. Lens opacity greater than grade 2 on any Lens Opacities Classification System III (LOCS III) criterion, or other media opacity/nystagmus that might interfere with quality retinal imaging 6. Diabetes 7. Vitamin A deficiency 8. Other significant systemic disease or medication known to affect visual or retinal function 9. Systemic illness that would compromise participation in a 1-year trial 10. Actively under treatment for cancer 11. Diagnosed with cancer with ocular involvement 12. Insufficient English language comprehension 13. A possible cognitive impairment as determined using an abridged Mini-Cog. This is defined as a score of less than 3. 14. Known or suspected seafood allergy 15. Photosensitive epilepsy 16. Currently treated with warfarin or other vitamin K antagonist 17. Participation in any other interventional trial within 30 days prior to entering this trial 18. Men who are planning a pregnancy with their partner or have partners who are women of childbearing potential 19. Taking supplements containing saponins (e.g. ginseng) 20. Unable to consume the IMP or placebo for a period of longer than 24 hours during the treatment window (for example a prolonged fast or repeated 24-hour fast) 21. Participants undergoing planned, forthcoming major surgical interventions Previous participant exclusion criteria: 1. Ocular pathology in the study eye (or in either eye for genetic conditions or glaucoma), other than age-related macular degeneration, which may affect visual function 2. Intraocular pressure of 24 mmHg or greater 3. Grade <2 van Herick or history of allergic reaction to dilating eye drops 4. Unable to classify AMD grade 5. Lens opacity greater than grade 2 on any Lens Opacities Classification System III (LOCS III) criterion, or other media opacity/nystagmus that might interfere with quality retinal imaging 6. Diabetes 7. Vitamin A deficiency 8. Other significant systemic disease or medication known to affect visual or retinal function 9. Systemic illness that would compromise participation in a 1-year trial 10. Actively under treatment for cancer 11. Diagnosed with cancer with ocular involvement 12. Insufficient English language comprehension 13. A possible cognitive impairment as determined using an abridged Mini-Cog. This is defined as a score of less than 3. 14. Known or suspected seafood allergy 15. Photosensitive epilepsy 16. Currently treated with warfarin or other vitamin K antagonist 17. Participation in any other interventional trial within 30 days prior to entering this trial 18. Women who are pregnant, lactating or planning a pregnancy, or men who have a partner who is planning a pregnancy 19. Taking supplements containing saponins (e.g. ginseng) 20. Unable to consume the IMP or placebo for a period of longer than 24 hours during the treatment window (for example a prolonged fast or repeated 24-hour fast) 21. Participants undergoing planned, forthcoming major surgical interventions |
| Date of first enrolment | 15/11/2024 |
| Date of final enrolment | 01/09/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Maindy Road
Cardiff
CF24 4HQ
United Kingdom
London
EC1V 0HB
United Kingdom
Sponsor information
University/education
Research and Innovation Services
7th Floor, McKenzie House
30-36 Newport Road
Cardiff
CF24 0DE
Wales
United Kingdom
| Phone | +44 (0)29 208 79130 |
|---|---|
| shawc3@cardiff.ac.uk | |
| Website | http://www.cardiff.ac.uk/ |
"ROR" |
https://ror.org/03kk7td41 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Standard principles in accordance with the policy of the International Committee of Medical Journal Editors will be followed. The Chief Investigator (CI) will coordinate the dissemination and writing of data from the main trial. Authorship at the head of the primary results paper will be the CI as the main author followed by the other authors in alphabetical order. Or, if the CI is not the main author, the main author will be first with the CI as the last and corresponding author and other authors arranged alphabetically. All other contributors will be listed at the end of the main paper, with their contribution identified. All publications and presentations relating to the trial will be authorised by the Trial Management Group in accordance with the trial publication policy. The results of the trial will be disseminated regardless of the magnitude or direction of effect, via a full report to the funder and in peer-reviewed journal publications. Participants will be able to view a summary of trial publications if they wish, which will contain full references on the trial website. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
01/10/2024: The recruitment start date was changed from 01/09/2024 to 15/11/2024.
25/07/2024: The following changes were made:
1. The recruitment start date was changed from 01/08/2024 to 01/09/2024.
2. The recruitment end date was changed from 31/08/2024 to 01/09/2025.
3. The participant inclusion and exclusion criteria were changed.
4. The lower and upper age limit numbers and units were added.
5. The intention to publish date was changed from 31/03/2026 to 30/06/2027.
02/05/2024: Internal review.
17/04/2023: Trial's existence confirmed by Health Research Authority (HRA) (UK).
