European Nutrition in Glaucoma Management Trial

Study Overview
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Brief Summary
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European Nutrition in Glaucoma Management (ENIGMA) trial will evaluate the effect of 18-month supplementation with lutein, zeaxanthin and meso-zeaxanthin on macular pigment (MP) levels, vision, cognition and serum biomarkers of inflammation and oxidative stress in glaucoma patients. This study comprises a randomised, placebo controlled and double masked clinical trial designed to establish MP response to supplementation with lutein, zeaxanthin and meso-zeaxanthin over an 18-month period. The study will also investigate the relationship between macular pigment, cognitive function, oxidative stress and inflammation, and determine the impact of dietary supplementation on vision, retinal structure, quality of life and cognitive function among glaucoma subjects.

Detailed Description
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This is a research study looking at the effects of dietary MP supplementation in glaucoma patients. Glaucoma can cause irreversible visual impairment. Current treatment modalities only halt disease progression and do not improve visual function. It is important to understand that poor visual function can have major consequences to an individual's day-to-day tasks such as increased risk of falls and automobile accidents. Disability glare is commonly experienced by eye disease patients, including those with glaucoma, and has been shown to be present even in those who are mildly affected by the disease. MP is a blue-light filter that plays an important role in visual performance including glare sensitivity. Moreover, MP is a potent antioxidant, and it is widely known that oxidative stress is involved in the pathogenesis of glaucoma, both at the level of retinal ganglion cells and trabecular meshwork. Glaucoma and cognitive decline are both neurodegenerative processes that share several antecedents. The clustering of degenerative disorders towards the end of life is thought to be the result of cumulative and lifelong oxidative injury, and is consistent with the free radical theory of aging. Observational studies have revealed links between the two conditions. The commonalities between glaucoma and cognitive decline, including their shared risk factor profile and pathophysiological pathways, suggest a role for exploring common mechanisms and perhaps even a shared therapeutic approach. The purpose of this study is to investigate the effects of dietary MP supplementation on MP levels, serum biomarkers of inflammation and oxidative stress, vision, retinal structure and cognition in glaucoma patients. Study design 64 glaucoma participants Treatment arm: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin - 2/3 Placebo arm: Identical capsule containing no active ingredients - 1/3 Duration of intervention: 18 months At baseline, all glaucoma participants undergo detailed vision assessments including visual acuity, microperimetry, measurement of macular pigment optical density (MPOD) with dual-wavelength fundus autofluorescence technique, optical coherence tomography scans, contrast sensitivity testing with and without glare, photostress recovery time, pupil reaction assessment, lens fluorescence measurement and fill out vision-related and dietary questionnaires. Patients also undergo detailed cognitive assessment including the flanker task, sound-induced flash illusions task, verbal fluency (FAS and animal fluency tests), SKT (short cognitive assessment) and MMSE (mini-mental state examination) tests which provide measures of reaction time, short-term memory, multisensory integration and attention. A blood sample is also collected for analysis of oxidative stress and inflammatory biomarkers. After the baseline assessments, glaucoma participants are randomised (2:1) to receive a dietary MP supplementation or placebo for 6 months. Each daily dose of the supplement contains 10mg Lutein, 10mg meso-Zeaxanthin and 2mg Zeaxanthin in a softgel capsule. The intervention consists of a daily oral consumption of one softgel capsule (recommended to be consumed with food) for a period of 18 months, with patients compliance checks and re-supply of supplement every 6 months. The placebo looks identical to the active supplement in its preparation size, colour, smell and taste. It contains no active ingredients.

Official Title
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European Nutrition in Glaucoma Management Trial

Conditions
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Glaucoma, Open-Angle

Intervention / Treatment
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* Dietary Supplement: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Open-angle glaucoma patients aged 18 years or older Primary open-angle glaucoma (POAG) Normal-tension glaucoma (NTG) Pseudoexfoliative glaucoma Pigment dispersion glaucoma Best corrected visual acuity of better than 6/12 in the study eye (logMAR <0.3) Either gender Able to give informed consent, make the required study follow-up visits and adhere to trial protocol Exclusion Criteria: Underlying ocular disease such as age-related macular degeneration, diabetic retinopathy or moderate to significant cataract (patients with established cataract who are likely to progress) Best corrected visual acuity of worse than 6/12 in the study eye (logMAR > 0.3) History of diabetes mellitus, any type of dementia (e.g. Alzheimer's has been shown to be associated with lower macular pigment levels) or other significant systemic condition that might affect capacity to complete the trial MMSE score < 26 Individuals taking dietary macular pigment supplements (containing lutein, zeaxanthin and meso-zeaxanthin, such as MacuShield, Ocuvite Lutein/Complete, I-Caps etc.) in the past 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Softgel capsules: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin once a day with a meal for 18 months | Dietary Supplement: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin<br>* This is a lutein (10mg), zeaxanthin (2mg) and meso-zeaxanthin (10mg) one-a-day food supplement which combines all three macular carotenoids. These three nutrients are found at the back of the eye, at the macula, where they form the macular pigment (yellow colour). Meso-zeaxanthin is particularly concentrated at the centre of this pigment. Lutein and zeaxanthin can be found in fruits and dark green leafy vegetables and meso-zeaxanthin is present in some species of fish and seafood.<br>|
| Placebo Comparator: Placebo<br>Identical capsule containing no active ingredients | Other: Placebo<br>* Softgel capsule containing sunflower oil (no active ingredients)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MPOD in response to treatment from baseline at 18 months | Change in MPOD measured at each study visit from baseline to 18 months will be evaluated between active and placebo arms | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in multisensory integration from baseline following 18 months supplementation | Multisensory integration will be assessed using a sound-induced flash illusions task (SIFI). Change in SIFI scores will be assessed between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in flanker task scores (reaction time and attention) from baseline following 18 months supplementation | Change in flanker task scores will be assessed between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in SKT (Syndrom-Kurztest) score from baseline following 18 months supplementation | SKT is a short cognitive battery of tests that evaluates general cognitive function. Change in SKT score will be assessed between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in verbal fluency (FAS score) from baseline following 18 months supplementation | Change in verbal fluency assessed using the FAS test will be evaluated between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in verbal fluency (animal fluency test) from baseline following 18 months supplementation | Change in verbal fluency assessed using the animal fluency test will be evaluated between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in Visual Acuity in response to treatment from baseline at 18 months | Change in Visual Acuity will be evaluated between active and placebo treatment arms from baseline to 18 months | 18 months | 
| Change in Contrast Sensitivity in response to treatment from baseline at 18 months | Change in Contrast Sensitivity under photopic and mesopic conditions at 1.5, 3, 6, 12 and 18 cycles per degree will be evaluated between active and placebo treatment arms from baseline to 18 months, using the FACT device | 18 months | 
| Change in incremental light sensitivity in response to treatment from baseline at 18 months | Change in Microperimetry average threshold will be evaluated between active and placebo treatment arms from baseline to 18 months, using the Maia device | 18 months | 
| Change in Retinal Thickness parameters in response to treatment from baseline at 18 months | Change in Retinal Thickness parameters will be evaluated between active and placebo treatment arms from baseline to 18 months, using the Spectralis OCT device | 18 months | 
| Change in serum biomarkers of inflammation (C-reactive protein) from baseline following 18 months supplementation | Inflammation will be assessed using the C-reactive protein biomarker measured in serum | 18 months | 
| Change in serum biomarkers of oxidative stress (Oxidized LDL) from baseline following 18 months supplementation | Oxidative stress will be assessed using the Oxidized LDL biomarker measured in serum | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multisensory integration, macular pigment, lutein, zeaxanthin, meso-zeaxanthin, cognitive function, glaucoma