Nicotinamide Riboside Oral Supplementation in Macula Off Retinal Detachment

Официальное название

A Randomised Double-Masked Placebo-Controlled Trial of Nicotinamide Riboside Oral Supplementation in Macula Off Retinal Detachment

Обзор

Retinal detachment occurs when fluid separates the retina (a thin, light sensing tissue) from its usual attachment at the back of the eye. If detached, these retinal cells lose their normal blood supply and begin to die, which is the primary cause of vision loss in retinal detachment. The 'macula' refers to the very centre of the retina, with the highest density of retinal cells, most responsible for vision. Significant vision loss occurs when this part of the retina becomes separated (termed a 'macula-off retinal detachment'). Typically, surgery is required to repair the retinal detachment. Supporting the health of retinal cells at the macula may prolong their survival after detachment and their recovery postoperatively. Recent evidence has shown that boosting our nicotinamide adenine dinucleotide (NAD+) levels may improve the health of these cells and prolong their survival if detached. Oral Nicotinamide Riboside (NR) is converted into NAD+, and while not studied for macula-off retinal detachments, has been safely used in a range of other conditions. This study is designed to help evaluate the safety and tolerability of NR to help preserve vision in people diagnosed with macula-off retinal detachment. This study drug is given as an oral supplement (tablet) at the time of retinal detachment diagnosis, and daily for 20 weeks thereafter. The drug aims to prolong survival of cells in the retina (and macula) and their recovery after surgery. The long-term goal of this treatment is to reduce loss of vision after retinal detachment. The researchers will compare NR to a placebo (a look-alike substance that contains no drug) to see if NR has a positive effect on photoreceptor survival and quality of vision postoperatively. NR has been approved by the Therapeutic Goods Administration in Australia for many purposes but has not been approved for use in retinal detachment treatment.

Вмешательства

• Пищевая добавка Nicotinamide Riboside
  Oral Nicotinamide Riboside, 2g daily for 4 weeks followed by 1g daily for 16 weeks
• Другое Placebo
  Matched placebo
• Процедура Vitrectomy and Gas tamponade
  Standard of care Vitrectomy surgery for retinal reattachment

Первичные конечные точки

• Best-corrected Visual Acuity [Срок оценки: 20 weeks postoperatively]
• Microperimetry [Срок оценки: 20 weeks postoperatively]
• Contrast sensitivity [Срок оценки: 20 weeks postoperatively]

Вторичные конечные точки (1)

• Integrity of the photoreceptor layer on optical coherence tomography [Срок оценки: 20 weeks postoperatively]

Критерии участия

Критерии включения

• Age ≥ 18 years old
• Able to give informed consent and comply with all study visits and procedures.
• Present within 10 days of macula-off retinal detachment (based on patient-reported history of loss of central vision)
• Present to the hospital with a visual acuity of hand motion or better in the study eye
• Have had previous cataract surgery in the study eye
• Have clinical indication for standard retinal reattachment surgery by means of a pars plana vitrectomy and gas tamponade
• In the opinion of the investigator, be able to safely undergo all study procedures.

Критерии исключения

• Any known significant ocular disease in the study eye (e.g., cornea opacity) which, in the opinion of the investigator, would preclude a visual acuity of at least 6/7.5 (20/25) following successful vitrectomy or limit adequate visibility of the retina.
• Any other ocular pathology in the study eye requiring treatment with topical ophthalmic drops or intravitreal injection.
• History of previous ocular surgery in the study eye other than uncomplicated cataract surgery with posterior chamber intraocular lens and intact posterior capsule or a refractive surgery (surgery must have occurred at least 3 months prior to the baseline visit).
• Participation in other clinical trials or use of any other investigational drugs or devices within 3 months prior to study participation.
• Females who are pregnant or lactating and women of childbearing potential.
• Known retinopathy, known hepatic disease (or history of significant chronic liver disease), or known renal disease. Patients Participants with diabetes and no known retinopathy may be enrolled.
• History of uncontrolled hypertension.
• History of stroke, transient ischemic attack, or major cardiac surgery within 3 months prior to study, or current treatment for systemic infection.
• Any ocular or systemic condition that in the opinion of the investigator could compromise the safety of the patientparticipant, or may interfere with the safety and tolerability assessments or study procedures of the trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 5 центров

• Centre for Eye Research Australia — East Melbourne
• Cerulea — East Melbourne
• The Royal Victorian Eye and Ear Hospital — East Melbourne
• Dr David Fabinyi — Geelong
• Dr David Sousa — Geelong

Публикации

• Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7. PMID 29599478
• Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015 Oct 22;373(17):1618-26. doi: 10.1056/NEJMoa1506197. PMID 26488693
• Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948. PMID 27721479
• Bai S, Sheline CT. NAD(+) maintenance attenuates light induced photoreceptor degeneration. Exp Eye Res. 2013 Mar;108:76-83. doi: 10.1016/j.exer.2012.12.007. Epub 2012 Dec 26. PMID 23274583
• Zhang X, Henneman NF, Girardot PE, Sellers JT, Chrenek MA, Li Y, Wang J, Brenner C, Nickerson JM, Boatright JH. Systemic Treatment With Nicotinamide Riboside Is Protective in a Mouse Model of Light-Induced Retinal Degeneration. Invest Ophthalmol Vis Sci. 2020 Aug 3;61(10):47. doi: 10.1167/iovs.61.10.47. PMID 32852543

Идентификаторы

NCT: NCT06587945 · NOMAD · U1111-1307-8530

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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