The Glaucoma Nicotinamide Trial (TGNT)

The Glaucoma Nicotinamide Trial - A Prospective, Randomized, Placebo-controlled, Double-masked Trial

The Glaucoma Nicotinamide Trial (TGNT) is a prospective, randomized, placebo-controlled double-masked clinical trial composed of two cohorts; The Swedish Glaucoma Nicotinamide Trial (SGNT) and the Vitamin B3 In Glaucoma Study (VBIGS). Patients with open-angle glaucoma (OAG) will be randomized to receive either Nicotinamide or placebo through block randomization stratified by glaucoma subtype with a 1:1 allocation.

Study Overview

• Status: Recruiting
• Conditions: Glaucoma
• Intervention / Treatment: Dietary supplement: Nicotinamide; Other: Placebo

Detailed Description

The treatment arms that included patients will be randomized into are either Nicotinamide tablets 1.5g for 6 weeks and then 3.0g onwards or true placebo tablets. A major difference between the SGNT and VBIGS is that in SGNT untreated newly diagnosed glaucoma patients will be included whereas in VBIGS glaucoma patients with intraocular pressure lowering treatment will be included. Also, in SGNT an additional non-blinded arm with healthy subjects will receive Nicotinamide tablets 1.5g for 6 weeks and then 3.0g onwards. For participants where both eyes are eligible, both will be included.

The primary endpoint is visual field progression change over two years.

• Study Type: Interventional
• Enrollment (Estimated): 660
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gauti Jóhannesson; Phone Number: +46907850000; Email: gauti.johannesson@umu.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • S:t Eriks Eye Hospital
    • Contact: Amelie Botling Taube
  • Umeå, Sweden
    • Recruiting
    • Umea University
    • Contact: Gauti Johannesson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

SGNT:

Inclusion Criteria:

• Adult participants (>18 years) with newly-diagnosed and previously untreated POAG or PEXG in one or both eyes. Glaucoma is defined as reproducible visual field (VF) defects that cannot be explained by other disease or damage, and a suspect/abnormal optic nerve head and/or nerve fibre layer defect.
• Participants need to have visual acuity of Snellen ≥ 6/12 (0.5) or better.
• Have performed at least two reliable VFs (SITA-Fast 24-2), with <33% fixation losses and <15% false positives

Exclusion Criteria:

• VF damage worse than -10dB in the best eye and -16dB in the worse eye or a paracentral spot with -10dB or less in any eye),
• IOP >35mmHg in any eye or a mean IOP of 30mmHg or higher (two measurements), •inability to perform VFs,
• pregnancy/breastfeeding,
• those unwilling to abstain from NAM supplements,
• allergic to NAM/niacin,
• diagnosed with cancer in the last 5 years (except treated basal or squamous cell carcinoma),
• a history of liver disease or stomach ulcers,
• disease that prevents long-term follow-up,
• neurologic or other non-glaucomatous conditions apart from cataract that may affect the VF, •inability to understand and speak Swedish or English,
• a history of intraocular surgery (apart from uncomplicated cataract surgery) and
• diseases that are known to affect retinal function (e.g. > mild age-related macular degeneration, > stage I diabetic retinopathy).

VBIGS:

Inclusion Criteria:

• Patients aged 18 years or older, with definitive, treated POAG including normal tension glaucoma, PEXG in both eyes
• Best-corrected visual acuity ≥ 6/18
• Severity of visual field loss, MD between -3 and -18 dB. This range includes people with moderate disease which optimises detection of progression.
• Patient must have performed at least two reliable VFs (24-2), with <33% fixation losses and <15% false positives.
• Previous selective laser trabeculoplasty is acceptable (IOP-lowering laser treatment) if 3 or more months prior, and normal liver function tests.
• Those taking NAM already will undergo a 1-month washout period before commencing the study.

Exclusion Criteria:

• Patients with a history of hepatic disease, gout, visually significant cataracts, other conditions that can affect VF results, cataract surgery in the last 3 months or glaucoma filtration surgery in last 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicotinamide; Participants will receive 750mg nicotinamide tablets 1+1 per day (1.5g) for 6 weeks and after that 2+2 per day (3.0g).	Dietary supplement: Nicotinamide; Study tablets for nicotinamide are produced by Blackmores Ltd.
Placebo Comparator: Placebo; Participants will receive 750mg placebo tablets 1+1 per day for 6 weeks and after that 2+2 per day.	Other: Placebo; Study tablets for placebo are produced by Blackmores Ltd.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual field progression	Change in rate of progression between the two study arms	Two years

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Karolinska Institutet; Lund University; Göteborg University; Linkoeping University; University of Adelaide; University of Melbourne; Singapore National Eye Centre; Duke-NUS Graduate Medical School; Centre for Eye Research Australia

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Glaucoma; Neuroprotection; Nicotinamide
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: TGNT; SGNT (Other Identifier: Umeå University); VBIGS (Other Identifier: Centre for Eye Research Australia)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No