NicotinAMide in Glaucoma (NAMinG): a randomised, placebo-controlled, multi-centre, Phase III trial

Plain English Summary

Background and study aims
Glaucoma is a long-term eye disease which can cause permanent loss of sight and sometimes blindness. It is the world’s most common cause of irreversible blindness. Vision loss happens because of damage to the important nerve at the back of the eye called the optic nerve. Most people receiving current glaucoma treatments (eye drops or laser therapy) do not experience noticeable vision loss. However, a significant minority do lose vision. We cannot cure glaucoma, but we can treat it so that the damage is slowed down or stopped, so more vision is kept for longer. There are 2 big risk factors of Glaucoma - being an older person and having high pressure inside the eye. High pressure damages the optic nerve and being older makes this damage more likely. Some people get glaucoma even if they have normal eye pressure so we think that the optic nerve in some people is more easily damaged. At the moment, we cannot tell who these people are. Recent research has looked at parts of cells called ‘mitochondria’. These produce energy and might affect how likely it is that vision could be damaged by eye pressure. The nerve cells in the eye need a great deal of energy to function and survive. Vitamin B3, also known as nicotinamide (NAM), may improve the way mitochondria work. This research study wants to know if NAM treatment can protect against people losing sight because of glaucoma getting worse.

Who can participate?
Patients aged 18 years or older, who have been recently diagnosed (within the last 12 months) with early to moderate open-angle glaucoma (OAG) in at least one eye.

What does the study involve?
There will be two groups, but all will receive normal care to lower eye pressure (drops or laser); one group will receive NAM and the other group will receive dummy treatment (placebo). The trial will be randomised. Vision will be monitored through standard of care eye tests, questionnaires will be completed, blood tests will be required and there will be more visits to the hospital (3 extra than normal over 30 months). A successful outcome would lead to greatly reduced sight loss in glaucoma. Treatment with pills may also be easier for patients and would significantly reduce cost to NHS.
There is a total of 8 clinic visits, so 3 extra visits in addition to the participants routine visits. This has been reduced from the original concept so as not to be too onerous based on the feedback received from a patient web focus group. The visits, where possible, have been kept in line with normal routine care. Participants will be reimbursed (up to £30) for the travel costs incurred in attending the additional visits.

What are the possible benefits and risks of participating?
Benefits:
There is no guarantee that the Nicotinamide treatment will benefit patients however, the information we get from the trial will help the trial team find out if Nicotinamide provides better outcomes for people with glaucoma and therefore, will improve treatment for all glaucoma patients in the future.
Risks:
Adverse Events/Side Effects:
Nicotinamide (NAM) is known to be well-tolerated and the great majority of people taking NAM at the doses prescribed in the trial have no side effects. A patient attendee from the web focus group mentioned that the trial is particularly attractive as the treatment is non-invasive with a low risk of side effects. However, in any clinical trial, there is a chance of experiencing side-effects from the trial medications. The possible (including very rare) side effects of NAM are: flushing, gastro-intestinal symptoms, liver function test abnormalities, eye symptoms, fatigue, headaches, and low insulin sensitivity. Participants will be informed of the risks during the informed consent process and they will be asked to record in their dosing dairy any side effects they experience, which will be reviewed regularly at each clinic visit. The research team will also be in constant contact with the participants via telephone calls scheduled in between the clinic visits. Participants will also be informed to notify the research team should they experience any serious side effects/serious adverse events or if they are hospitalised. Participants will be provided with an alert card, which they will carry with them at all times and it will contain contact details of the trial team during in-office/out-of-office hours.

Interactions with other medications:
There are some medications that can cause side-effects when taken with NAM. Participants will be asked to take all their medications, including supplements to their Screening visit so that the research team can review their concomitant medication before entering the trial. Participants will be instructed to inform the research team of all medications (prescribed and non-prescribed) that they take during the course of trial and this will be reviewed at each clinic visit. There are some medications that preclude the participant from entering the trial and the research team will inform the participant of this and this information will be detailed in the Participant Information Sheet (PIS). A Participant Medication Checklist Letter will also be provided to participants, alongside their appointment letter for their Screening visit as a reminder to bring all their medication and those medications that are not permitted in the trial.

Pregnancy:
We do not know if NAM is a risk for a pregnant woman, an unborn baby, or a breastfeeding child, so pregnant and breastfeeding women will not be allowed to take part in the trial. Male and female participants will be asked to take highly effective contraceptive measures during the course of the trial starting from the time of informed consent and for 30 days after their last administration of the trial drug. Urine pregnancy tests for women of child bearing potential (WOCBP) will be performed at each clinic visit.

Blood samples:
The collection of blood samples can be uncomfortable, but rarely results in any serious problems. Reported side effects include feeling light-headed or faint, bruising and/or discomfort around the needle site. Every effort will be made by the research team to minimise this.

Visual field assessment:
Visual field assessments occur during clinic visits as part of standard of care, however there are some trial visits where the visual field assessment is required to be repeated twice. A 30 minute break will be given in between these repeated tests to avoid long durations of assessing the eyes and to ensure the correct visual field tests are performed, a participant visual field reminder card will be supplied to the participant by the research team, which they can bring to each clinic visit and hand to the technician performing the visual field assessment.

Where is the study run from?
UCL Comprehensive Clinical Trials Unit (UK)

When is the study starting and how long is it expected to run for?
July 2023 to November 2026

Who is funding the study?
NIHR

Who is the main contact?
Prof. David Garway-Heath, d.garway@ucl.ac.uk

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• United Kingdom

Study participating centres

Sponsor information

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN16435278_PIS_V2.0_04Aug23.pdf

ISRCTN16435278_PROTOCOL_V2.0_05Sep23.pdf

Editorial Notes

30/12/2024: The following changes were made to the study record:
1. The recruitment start date was changed from 31/08/2023 to 18/01/2024.
2. The recruitment end date was changed from 31/12/2024 to 31/05/2025.
3. The intention to publish date was changed from 30/11/2027 to 31/01/2028.
01/03/2024: The following changes were made to the study record:
1. The public title was changed from 'Nicotinamide in Glaucoma' to 'NicotinAMide in Glaucoma (NAMinG): a randomised, placebo-controlled, multi-centre, Phase III trial'.
2. The scientific title was changed from 'Nicotinamide in Glaucoma (NAMinG); A randomised, placebo-controlled, multi-centre, Phase III trial' to 'A Phase III, double-masked, randomised, placebo-controlled trial investigating the safety and efficacy of nicotinamide (NAM) to slow visual field loss in adults with open-angle glaucoma'.
3. EudraCT number and ethics approval details added.
4. Participant information sheet uploaded.
01/12/2023: Internal review.
14/07/2023: Trial's existence confirmed by NHS HRA.