Major NIHR grant awarded to trial a form of vitamin B3 as a treatment for glaucoma

A team led by Professor Ted Garway-Heath at the UCL Institute of Ophthalmology (IoO) and Moorfields Eye Hospital has been awarded a £1.9 million grant for a major four-year clinical trial to test the effectiveness of nicotinamide (NAM), a form of vitamin B3, as a treatment for glaucoma.

The trial will eventually recruit 496 glaucoma patients across seven UK sites, with a pilot study starting at Moorfields and Kings College Hospital in London along with a third site yet to be confirmed. It will evaluate whether NAM, which replenishes molecules important for the functioning of mitochondria (the powerhouses of cells), protects glaucoma patients from progressive vision loss.

The trial builds on collaborative research at Moorfields, UCL IoO and the UCL Queen Square Institute of Neurology (IoN) showing that patients with both high- and low-tension glaucoma have lower mitochondrial function than healthy patients; and also that patients with ocular hypertension (higher than normal pressure inside the eye), but no signs of progression to glaucoma, have higher mitochondrial function.

Prof. Ted Garway Heath
Prof. Ted Garway-Heath leads the team for the new trial.
graph showing technical read out from the Seahorse Analyser
Graph showing a read-out from a Seahorse Analyzer, which will aid the researchers in this trial

The study will measure the impact of NAM on the capacity of mitochondria in peripheral blood lymphocytes (freely circulating white blood cells) to produce adenosine triphosphate (ATP), which provides energy to help cells function. The study will also investigate biomarkers (biological signs) that can predict disease progression for glaucoma.

Starting in August 2022, the trial will recruit a diverse group of patients recently diagnosed with glaucoma at NHS sites around the country. If treatment with NAM proves successful, it could significantly reduce the damage to vision caused by glaucoma and the cost of treatment for the NHS.

The trial has been funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme. The programme funds ambitious studies that evaluate interventions that have the potential to make a significant change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care. Within these studies, EME supports research in the mechanisms of diseases and treatments. EME is a partnership between the Medical Research Council and the NIHR.

The new study will be based primarily at UCL IoO, as it has recently acquired a Seahorse Analyzer (with funding from Moorfields Eye Charity), a machine that allows scientists to look at mitochondrial function within cells the basis for much of this study.

Seahorse Metabolic Analyser
A Seahorse Analyzer

About glaucoma

Glaucoma is a common eye condition in which the optic nerve, which connects the eye to the brain, becomes damaged. The most important risk factors are high pressure in the eye and older age. It is the world’s most common cause of irreversible blindness and affects 1 in 50 people aged over 50, rising to 1 in 20 in people aged over 80. Sometimes referred to as “the silent thief of sight”, glaucoma often has no symptoms until a considerable amount of vision has been permanently lost. Both eyes are usually affected.

Current treatment for glaucoma includes eye drops, laser treatment and surgery. These treatments aim to reduce pressure in the eye, thereby reducing damage to the optic nerve. Although we cannot cure glaucoma, current treatments can slow and sometimes halt its progression. However, many people’s condition worsens even with treatment, and some people develop glaucoma with normal eye pressure. Currently, doctors cannot identify who these people will be before treatment.

Prof. Ted Garway-Heath, lead applicant for the grant, said:

“We hope to find a treatment that isn’t directed at pressure in the eye, but that addresses the susceptibility of the patient to glaucoma. We also hope to identify a blood test to identify which patients will benefit from the new treatment.”

Leading the clinical trial alongside Prof. Garway-Heath is Gerassimos Lascaratos, consultant eye surgeon at King’s College Hospital. The other principal investigators are James Kirwan at Portsmouth Hospitals, David Broadway at Norfolk and Norwich University Hospitals, Rupert Bourne at the Cambridge Eye Research Centre (Cambridge University Hospitals), Anthony King at Nottingham University Hospitals and Augusto Azuara-Blanco at Queen’s University Belfast.

Background to the trial

In recent years, researchers have looked at how mitochondria – parts of cells that produce energy – affect how vison could be damaged by eye pressure. The nerve cells in the eye and other cells in the retina need a large amount of energy to function and survive. Older age is associated with mitochondria everywhere in the body working less well and producing less energy.

labelled diagram of an animal mitochondria
Diagram of a labelled mitochondria. Image from Wiki Commons

This new study is the result of a longstanding collaboration between UCL IoO and the UCL IoN, both part of the UCL Faculty of Brain Sciences. The co-applicants for the grant are Prof. Garway-Heath, Tony Schapira (Professor of Neurological Science at UCL IoN), and Gerassimos Lascaratos (whose PhD was jointly supervised by Profs. Garway-Heath and Schapira in 2011-14).

Pre-clinical models of glaucoma have looked at NAM and its effect on mitochondria. Two subsequent small, short-term clinical trials in patients given high doses of NAM showed some increased visual function for a quarter of the people with glaucoma who took part*.

In this new randomised trial, participants will receive standard care eye pressure lowering for their glaucoma. Half will then be given NAM and the other half will be given placebo (inactive substitute) pills. The results will also help to show:

1. If it is possible to predict how quickly glaucoma advances by looking at mitochondria

2. If NAM helps mitochondria work better

3. If NAM provides greater benefit to people with glaucoma whose mitochondria work poorly

We look forward to monitoring the trial over the coming years and reporting its outcomes, which may include a pathway to a safe, low-cost treatment to reduce blindness resulting from glaucoma and less reliance on costly eye drops.

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*Details of earlier trials of nicotinamide as a treatment for glaucoma:

i) Hui F, Tang J, Williams PA, McGuinness MB, Hadoux X, Casson RJ, Coote M, Trounce IA, Martin KR, van Wijngaarden P, Crowston JG. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial. Clin Exp Ophthalmol. 2020 Sep;48(7):903-914. doi: 10.1111/ceo.13818. Epub 2020 Jul 28. PMID: 32721104 -

ii) De Moraes CG, John SWM, Williams PA, Blumberg DM, Cioffi GA, Liebmann JM. Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2022 Jan 1;140(1):11-18. doi: 10.1001/jamaophthalmol.2021.4576. PMID: 34792559; PMCID: PMC8603231 -