Nicotinamide in Glaucoma (NAMinG): A Randomised, Placebo-controlled, Multi-centre, Phase III Trial

NCT05405868 | Recruiting Phase 3 DMC

• 1 other identifier: CTU/2020/365
• Study Type: interventional
• Target: 496
• Locations: 1 country
• Sites: 10

Brief Summary

Glaucoma is the leading cause of sight impairment and blindness worldwide. It is a long-term eye disease which can cause permanent loss of sight and sometimes blindness and affects 1 in 50 people over 50 years of age. Open-angle glaucoma (OAG) is the most common type of glaucoma. This tends to develop slowly over many years, caused by the drainage pathway in the eye gradually becoming blocked over time due to a build-up of fluid. This build-up causes pressure in the eye to increase (intra-ocular pressure (IOP)), which then damages the important nerve at the back of the eye called the optic nerve, resulting in vision loss. Current treatments offered for glaucoma (eye drops or laser surgery), aim to lower eye pressure and have shown to slow vision loss, however, visual disability and blindness rates remain unacceptably high and many patients continue to lose vision despite these treatments, suggesting that the optic nerve in some patients is more easily damaged. Recent research has looked at cells called 'mitochondria'. These cells produce most of the energy in the body, and the nerve cells in the eye need a lot of energy to function and survive. Nicotinamide (NAM) is a form of Vitamin B3 and evidence so far has shown that mitochondrial function can be improved with this treatment. The aim of this trial is to find out whether taking oral NAM when used with current standard treatment for lowering pressure in the eye, can reduce the amount of sight loss in recently diagnosed patients with OAG, and evaluate the long-term safety and effectiveness of NAM. The trial will use two groups of people recently diagnosed with glaucoma and who have normal care (drops or laser) to lower eye pressure. Using a method of randomisation (randomly allocated to each group using a computer system), one group will be given NAM and the other group will be given a placebo or 'dummy pill'. This is a double masked trial meaning the participant nor the Investigator will be told which treatment group patients have been allocated to.

Conditions

Glaucoma, Open-Angle

Keywords

Nicotinamide; Vitamin B3

Outcome Measures

Primary Outcomes (1)

• The difference between the treatment arms in change of Visual Field (VF) mean deviation (MD) at 27 months measured by the Humphrey Visual Field Analyser test

  The Humphrey Visual Field Analyser test is a diagnostic tool commonly used to assess the retina's ability to detect a light stimulus at specific points within the visual field, called retinal sensitivity. Participants will undergo visual field testing at Screening, Baseline, Months 3, 6,12,18, 24 and Month 27 using the Humphrey Visual Field analyser with the SITA Standard 24-2 programme. The results will be used to measure the progression of vision loss between the active arm (Nicotinamide) and the comparator (matching placebo) The primary endpoint will be analysed using a linear mixed model to estimate the difference between treatment groups in VF MD at 27 months. The model will include month 27 VF MD as the outcome and baseline VF MD, IOP-lowering treatment type (eye drops vs laser) and baseline serum NAM levels as covariates.

  Month 27; end of trial treatment

Secondary Outcomes (7)

• The difference in Visual Field (VF) mean deviation (MD) at 3 months (0-3 months - neuro-recovery) between the active treatment group and the placebo group, measured using the Humphrey Visual Field analyser test with the SITA Standard 24-2 programme

  From Baseline until Month 3

• Quality-of-Life outcome differences between the two treatment groups at baseline, month 3 and month 27, as measured by the descriptive system for health-related quality of life, EQ-5D-5L with additional vision specific questions.

  At Baseline, Month 3 and Month 27

• Quality-of-Life outcome differences between the two treatment groups at baseline, month 3 and month 27, as measured by the 15-item Glaucoma Quality of Life Questionnaire.

  At Baseline, Month 3 and Month 27

• The safety profile of high dose NAM, measured by liver function tests (LFTs) at Screening, Month 3 and Month 18

  At Screening, Month 3 and Month 18

• The safety profile of high dose NAM, measured from blood glucose test, HbA1c at Screening, Month 3 and Month 18

  At Screening, Month 3 and Month 18

Other Outcomes (22)

• The impact of NAM treatment on mitochondrial function in the active treatment group between baseline and month 27, measured using the Seahorse mitochondrial function test.

  From Baseline until end of trial treatment at Month 27

• The impact of NAM treatment on mitochondrial function in the placebo group between baseline and month 27, measured using the Seahorse mitochondrial function test.

  From Baseline until end of trial treatment at Month 27

• The association between lymphocyte mitochondrial function, measured by the Seahorse mitochondrial function test, and rate of visual field loss in the placebo group between baseline and month 27.

  From Baseline until end of trial treatment at Month 27

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Participants will receive Nicotinamide for up to 27 months (treatment period) in addition to an initial treatment of Standard of Care IOP- lowering therapy (prior to randomisation and start of trial treatment) . They will receive 1.5g/day for the first 6 weeks, then dose increase to 3.0g/day for remainder of the treatment period.

Drug: Nicotinomide

Matching Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo for up to 27 months (treatment period) in addition to an initial treatment of Standard of Care IOP- lowering therapy (prior to randomisation and start of trial treatment) . They will receive 1.5g/day for the first 6 weeks, then dose increase to 3.0g/day for remainder of the treatment period.

Drug: Matching placebo

Interventions

Nicotinomide DRUG

Nicotinamide tablets (750mg)

Nicotinamide

Matching placebo DRUG

Matching placebo

Matching Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have been recently diagnosed (within the last 12 months) with early to moderate open-angle glaucoma (OAG) in at least one eye (including primary OAG, normal tension glaucoma (NTG) and pseudoexfoliation glaucoma)
• Open angle on gonioscopy
• Adults aged 18 years or over
• Snellen visual acuity 6/12 or better in at least one eye meeting the visual field (VF) criteria
• Visual Field (VF) mean deviation (MD) no worse than -12dB in either eye
• A negative pregnancy test result at the screening and baseline visit prior to randomisation for women of childbearing potential
• Ability to provide informed consent to participate
• Able and willing to attend trial visits and comply with trial procedures for the duration of the trial

You may not qualify if:

• Pigment dispersion glaucoma
• Pregnancy (or planned pregnancy during the trial) and/or breastfeeding
• Women of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraception for the duration of the trial treatment and for the time period specified following last trial treatment administration.
• Current treatment with either isoniazid, pyrazinamide, carbamazepine, phenobarbital or primidone
• Current liver disease or laboratory results with elevated levels of liver transaminases (AST or ALT \>3 x ULN) at screening visit.
• Renal failure (eGFR \<30mL/min/1.73m²) at screening visit.
• Conditions affecting both eyes which may affect the Visual Field test result:
• Diabetic retinopathy or any other retinal disease causing VF loss
• Clinically relevant cataract (likely to require cataract surgery within the next 2 years)
• Dementia or other non-glaucomatous neurological disease causing VF loss
• Adnexal conditions causing VF loss (including but not limited to blepharochalasis)
• Diagnosed with cancer in the last 5 years (with exception of non-melanoma skin cancer).
• Any clinical condition that, in the investigator's opinion would make the participant unsuitable for the trial.
• Concurrently enrolled in any other interventional trial or participation in previous clinical trial of glaucoma.
• Current use of, and unwilling to abstain from, over-the-counter additional vitamin B3/NAM oral supplements (including skin preparations such as ointments/emulsions), Ginkgo Biloba and/or Coenzyme Q10 supplements, throughout the duration of their participation in the trial.

Sponsors & Collaborators

• University College, London: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (10)

Belfast City Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

NOT YET RECRUITING

Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 OQQ, United Kingdom

NOT YET RECRUITING

Queen Victoria Hospital NHS Foundation Trust

East Grinstead, RH19 3DZ, United Kingdom

RECRUITING

Royal Liverpool Hospital

Liverpool, L7 8XP, United Kingdom

NOT YET RECRUITING

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

RECRUITING

Barnet Hospital, Royal Free London NHS Foundation Trust

London, EN5 3DJ, United Kingdom

NOT YET RECRUITING

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

RECRUITING

Manchester Royal Eye Hospital

Manchester, M13 9WL, United Kingdom

NOT YET RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

NOT YET RECRUITING

Queen Alexandra Hospital

Portsmouth, PO6 3LY, United Kingdom

RECRUITING

MeSH Terms

Conditions

Glaucoma, Open-Angle

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases

Study Officials

• David Garway-Heath

  UCL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NAMinG Trial Team

CONTACT

0203 108 6148; cctu.naming@ucl.ac.uk

Felicia Ikeji

CONTACT

020 7679 9506; f.ikeji@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-masked
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomised 1:1 to receive oral Nicotinamide 3g/day or matching Placebo

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: June 6, 2022
• Study Start: January 18, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (10)