Glaucoma, Open-AngleENIGMANCT04460365
European Nutrition in Glaucoma Management Trial
A study testing 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin in people with Glaucoma, Open-Angle, run by Centre for Eye Research Ireland at 1 site in Ireland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glaucoma, Open-Angle
- What is being tested?
- 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteIreland
- Study dates
- 1 Oct 2017to 17 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
- Conditions
- Glaucoma, Open-Angle
- Being tested
- 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin, Placebo
- Keywords
- multisensory integration, macular pigment, lutein, zeaxanthin, meso-zeaxanthin, cognitive function, glaucoma
- Medical subject headings
- Glaucoma, Open-Angle, Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthinDietary supplement
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.
PlaceboOther
Softgel capsule containing sunflower oil (no active ingredients)
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Softgel capsules: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin once a day with a meal for 18 months Receives: Dietary Supplement: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin |
| Placebo | Placebo comparator | Identical capsule containing no active ingredients Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months
Secondary outcomes (11)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start1 Oct 2017
- Primary completion17 Sep 2020
- Study completion17 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glaucoma, Open-AngleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Eye Research Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Loughman, PhD, Principal investigator, Head of the Centre for Eye Research Ireland, Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04460365
- Sponsor's protocol ID
- 1/378/1535
- Acronym
- ENIGMA
- Status last verified
- Aug 2021
- First submitted
- 2 Mar 2020
- Last updated
- 6 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Loughman J, Loskutova E, Butler JS, Siah WF, O'Brien C. Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial. Ophthalmol Sci. 2021 Jul 11;1(3):100039. doi: 10.1016/j.xops.2021.100039. eCollection 2021 Sep.
PubMed 36247822
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- European Nutrition in Glaucoma Management Trial
- ClinicalTrials.gov ID
- NCT04460365
- Acronym / sponsor ID
- ENIGMA / 1/378/1535
- Conditions
- Glaucoma, Open-Angle
- Keywords
- multisensory integration, macular pigment, lutein, zeaxanthin, meso-zeaxanthin, cognitive function, glaucoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Centre for Eye Research IrelandUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 17 Sep 2020 (actual)
- Study completion
- 17 Sep 2020 (actual)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Dietary Supplement: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthinSoftgel capsules: 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin once a day with a meal for 18 months |
| Placebo | Placebo comparator | Other: PlaceboIdentical capsule containing no active ingredients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Open-angle glaucoma patients aged 18 years or older
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthinThis 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. | Dietary supplement | Active |
| PlaceboSoftgel capsule containing sunflower oil (no active ingredients) | Other | Placebo |
Primary outcome
Change in MPOD in response to treatment from baseline at 18 months
Time frame: 18 months
Change in MPOD measured at each study visit from baseline to 18 months will be evaluated between active and placebo arms
11 secondary outcomes
Change in multisensory integration from baseline following 18 months supplementation
Time frame: 18 months
Change in flanker task scores (reaction time and attention) from baseline following 18 months supplementation
Time frame: 18 months
Change in SKT (Syndrom-Kurztest) score from baseline following 18 months supplementation
Time frame: 18 months
Change in verbal fluency (FAS score) from baseline following 18 months supplementation
Time frame: 18 months
Change in verbal fluency (animal fluency test) from baseline following 18 months supplementation
Time frame: 18 months
Change in Visual Acuity in response to treatment from baseline at 18 months
Time frame: 18 months
Change in Contrast Sensitivity in response to treatment from baseline at 18 months
Time frame: 18 months
Change in incremental light sensitivity in response to treatment from baseline at 18 months
Time frame: 18 months
Change in Retinal Thickness parameters in response to treatment from baseline at 18 months
Time frame: 18 months
Change in serum biomarkers of inflammation (C-reactive protein) from baseline following 18 months supplementation
Time frame: 18 months
Change in serum biomarkers of oxidative stress (Oxidized LDL) from baseline following 18 months supplementation
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2021.
- Derived from this study: PubMed 36247822Loughman J, Loskutova E, Butler JS, Siah WF, O'Brien C. Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial. Ophthalmol Sci. 2021 Jul 11;1(3):100039. doi: 10.1016/j.xops.2021.100039. eCollection 2021 Sep.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Loughman, PhD principal investigator
Head of the Centre for Eye Research Ireland, Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 10 mg Lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin in people with Glaucoma, Open-Angle, run by Centre for Eye Research Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in MPOD in response to treatment from baseline at 18 months (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04460365, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2021.