ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000809336

Ethics application status

Approved

Date submitted

30/05/2017

Date registered

2/06/2017

Date last updated

6/07/2021

Date data sharing statement initially provided

15/03/2019

Date results provided

15/03/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The Effect of Vitamin B3 Supplementation in Glaucoma

Scientific title

A Prospective Study on the Effect of Nicotinamide Supplementation on Ocular Function and Structure in Glaucoma

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1197-0197

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Glaucoma

Condition category

Condition code

Eye

Diseases / disorders of the eye

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

International Nonproprietary Name (INN): nicotinamide
Intervention: daily nicotinamide supplementation for 12 weeks
Dose: accelerated dose from 1.5 grams daily for 6 weeks to 3 grams daily for 6 weeks
Mode of administration: oral tablet

Study design: 2 participant groups with cross-over study design. Participants are randomly assigned to receive either nicotinamide or placebo for 12 weeks, followed by a cross-over (i.e. those on nicotinamide first will switch to placebo and those on placebo first will switch to nicotinamide) for a further 12 weeks.
A washout period will not be utilised as the effect of nicotinamide does not have a persistent effect after intake is ceased. As participants will be seen in 6-weekly intervals, we do not expect a nicotinamide-induced effect on our measurements in the group that receives nicotinamide first and placebo second. As for those that receive placebo first, then a washout period is also unnecessary as no intervention has been given.

Adherence monitoring: remaining tablets will be counted at each visit, participants will be asked to log each time they forget a dose. To improve adherence, weekly reminders via phone, e-mail or text message will be sent, and a daily alarm set on participant's phone (if they have a smartphone). A minimum 70% compliance rate will be deemed acceptable, which approximately equates to forgetting to take the intervention twice a week.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo control (sugar pill) will be given to participants

Control group

Placebo

Outcomes

Primary outcome [1]

Short-term changes in retinal function after intervention, specifically visual field sensitivity assessed using perimetry (visual field machine)

Timepoint [1]

12 weeks after commencement of intervention

Primary outcome [2]

Short-term changes in retinal function after intervention, specifically changes to the photopic (light-adapted) electroretinogram (ERG). As nicotinamide leads to NAD+ repletion, which can drive energy repletion in the cells of the retina, the ERG can be affected in different ways. Specific parameters include amplitude and timing changes to the a-wave (photoreceptor), b-wave (bipolar cell) and photopic negative response (PhNR, retinal ganglion cell).

Timepoint [2]

12 weeks after commencement of intervention

Secondary outcome [1]

Short-term changes to retinal structure after intervention, specifically changes to retinal nerve fibre layer thickness measuring using optical coherence tomography (OCT)

Timepoint [1]

6 and 12 weeks after commencement of intervention

Secondary outcome [2]

Short-term changes in retinal function after intervention, specifically visual field sensitivity assessed using perimetry (visual field machine)

Timepoint [2]

6 weeks after randomisation and commencement of intervention

Secondary outcome [3]

Composite secondary outcome: change to intraocular pressure and/or ocular perfusion pressure (OPP). OPP is the balance between blood pressure and intraocular pressure.
Intraocular pressure will be measured using a rebound tonometer (iCare tonometer).
Blood pressure will be measured using a digital sphygmomanometer with inflatable arm cuff.

Timepoint [3]

6 and 12 weeks after commencement of intervention

Secondary outcome [4]

Timepoint [4]

6 weeks after randomisation and commencement of intervention

Secondary outcome [5]

Changes to the spectral characteristics of the retinal tissue assessed by hyperspectral imaging. Hyperspectral imaging provides information on the spectral characteristics of the retinal tissue, and may allow for detection of minor alterations to retinal structure, in particular, the retinal nerve fibre layer, which may not be seen using optical coherence tomography.
As hyperspectral imaging of the retina is a novel technique, images are post-processed offline in Matlab to analyse the spectral information in order to detect structural changes in the retina that may manifest after nicotinamide supplementation.

Timepoint [5]

6 and 12 weeks after commencement of intervention

Eligibility

Key inclusion criteria

- Diagnosis of primary open angle glaucoma by an ophthalmologist
- Recent (last 6 months), reliable visual field with mean defect equal to or better than -6 dB

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- those who are currently or intending to be pregnant/breastfeeding during the study
- those unwilling to abstain from other vitamin B supplements during the study period
- history of severe allergies or allergic reaction to nicotinamide or niacin
- those diagnosed with cancer in the last 5 years (except treated basal or squamous cell carcinoma)
- those with a history of liver disease
- those who cannot commit to the follow-up visits which occur at 6-weekly intervals over 24 weeks
- those who cannot provide informed consent
- eyes with a history of intraocular surgery in the past 6 months (uncomplicated cataract surgery within the last 3 months)
- systemic/ocular disease that are known to affect retinal function (e.g. age-related macular degeneration, demyelinating diseases, diabetic retinopathy)

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Participants will be randomly assigned to a numbered container which will contain either placebo or nicotinamide tablets.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Participants will be randomly assigned to receive either placebo or nicotinamide first by simple randomisation, using Microsoft Excel for random number generation

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample size calculation: Based on pilot data using the electroretinogram to detect functional changes in eyes after glaucoma surgery, an effect size of 0.56 was derived. A power calculation estimates that 48 eyes are required (power 80%, alpha = 0.05). To account for an attrition rate of 20%, we see to recruit 60 eyes all together with early glaucoma to effectively characterise the functional changes associated with NAD+ repletion with nicotinamide.

Statistics: Two-way repeated measures analysis of variance (RM-ANOVA) will be used to assess changes in the electroretinogram with nicotinamide, and the interaction nested within stimulus intensity. Two-way RM-ANOVA will also be used to assess the effect of nicotinamide on the electroretinogram, and the interaction nested within treatment change. Dunnett’s multiple comparisons tests will be used for post-hoc analysis to compare changes should they arise, between follow-up visits and baseline. One-way RM-ANOVA will be used to assess changes in individual locations on the 24-2 visual field. Correlations between the change in intraocular pressure and visual function will also be made in both nicotinamide and placebo groups.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

2/10/2017

Actual

9/10/2017

Date of last participant enrolment

Anticipated

27/04/2018

Actual

19/07/2018

Date of last data collection

Anticipated

31/10/2018

Actual

31/01/2019

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Victorian Eye and Ear Hospital - East Melbourne

Recruitment hospital [2]

Melbourne Eye Specialists - Fitzroy

Recruitment postcode(s) [1]

3002 - East Melbourne

Recruitment postcode(s) [2]

3065 - Fitzroy

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Centre for Eye Research Australia

Address [1]

32 Gisborne Street, East Melbourne, Victoria 3002

Country [1]

Australia

Primary sponsor type

Other

Name

Centre for Eye Research Australia

Address

32 Gisborne Street, East Melbourne, Victoria 3002

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Victorian Eye and Ear Hospital Human Research Ethics Committee

Ethics committee address [1]

32 Gisborne Street, East Melbourne, Victoria 3002

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/05/2017

Approval date [1]

29/06/2017

Ethics approval number [1]

17/1339H

Summary

Brief summary

This project aims to translate into the clinic a recently published study, demonstrating the protective role of vitamin B3 supplements (nicotinamide) in a mouse model of glaucoma. Glaucoma causes progressive loss of nerve tissue in the eye, and irreversible vision loss. This study investigates the short-term effect of taking nicotinamide supplements on the eye’s structure and function compared to placebo. 
Primary aims of this study include: 1) determining whether nicotinamide supplements in participants with glaucoma leads to short-term improvement in visual function measured using visual fields and the electroretinogram (ERG) and 2) determining whether nicotinamide leads to structural changes to the nerve tissue, imaged using hyperspectral imaging and optical coherence tomography. 
Participants diagnosed with glaucoma by an ophthalmologist will be invited to undertake the 24-week study with crossover design. They will be randomly assigned to take nicotinamide or placebo daily for 12 weeks. The ERG, visual fields and imaging are performed at baseline, 6 and 12-weeks post-intervention. Participants then crossover to take placebo or nicotinamide for another 12 weeks and the same measurements are repeated at 6 and 12-weeks post-intervention.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Jonathan Crowston

Address

Centre for Eye Research Australia
Level 7, Peter Howson Wing
32 Gisborne Street, East Melbourne, Victoria 3002

Country

Australia

Phone

+61 3 9929 8429

Fax

crowston@unimelb.edu.au

Contact person for public queries

Name

Flora Hui

Address

Centre for Eye Research Australia
Level 7, Peter Howson Wing
32 Gisborne Street, East Melbourne, Victoria 3002

Country

Australia

Phone

+61 3 99298114

Fax

f.hui@unimelb.edu.au

Contact person for scientific queries

Name

Jonathan Crowston

Address

Centre for Eye Research Australia
Level 7, Peter Howson Wing
32 Gisborne Street, East Melbourne, Victoria 3002

Country

Australia

Phone

+61 3 9929 8429

Fax

crowston@unimelb.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Neuroprotection in glaucoma: recent advances and clinical translation	2018	https://doi.org/10.1111/ceo.13336
Embase	Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.	2020	https://dx.doi.org/10.1111/ceo.13818

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically