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Age-Related Macular DegenerationNCT06391411

Effect of Micronutrient Supplementation on the Intestinal Microbiota in Patients With Age-related Macular Degeneration - The Gut-Retina-axis Study

A study testing a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) and anti-VEGF treatment in people with Age-Related Macular Degeneration, run by Azienda Ospedaliero-Universitaria Careggi at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly, characterized by multifactorial etiology. Recent evidence suggests a potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. Read more about this study

Who is it for?
Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for
Age-Related Macular Degeneration
What is being tested?
a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) and anti-VEGF treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteItaly
Study dates
1 Mar 2021to 1 May 2024
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 50 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Men and women >50 years of age.
  • Willingness to cooperate during the study and ability to follow guidelines and to complete all clinical visits
  • Ability to provide informed consent

Who cannot join

  • Use of antibiotics or continued use of pre- or probiotics in the 2 months before enrolment
  • Use of other treatments (medications or nutritional programs) that affect body weight, food intake, and/or energy expenditure
  • Diagnosis of any ocular disease.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Unit of Clinical Nutrition, University Hospital of Careggi

    Florence, 50134

Other trials in Italy

About this study

Official title: : Effect of Supplementation With Lutein, Zeaxanthin and Saffron on the Intestinal Microbiota in Patients Suffering From Age-related Macular Degeneration - The Gut-Retina-axis Study"

Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly, characterized by multifactorial etiology. Recent evidence suggests a potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. The investigators assessed the effects of a micronutrient mix containing lutein, zeaxanthin, and saffron, recognized for their anti-inflammatory properties, on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Thirty nAMD subjects were randomized to receive daily micronutrient supplementation along with anti-VEGF therapy or anti-VEGF treatment alone for 6 months. Ophthalmological assessments, anthropometric and biochemical measurements and stool samples were obtained pre- and post-treatment. Gut microbiota (GM) characterization was performed through 16S rRNA sequencing while short (SCFAs), medium (MCFAs) and long (LCFAs) chain fatty acids were analyzed with a gas chromatography-mass spectrometry protocol. nAMD patients exhibited reduced GM alpha diversity, altered taxonomic abundances and decreased total SCFA amount, coupled with elevated proinflammatory octanoic and nonanoic acids. Micronutrient supplementation led to improved visual acuity in comparison to the control group, along with the reduction in the total amount of MCFAs, metabolites exerting detrimental ocular effects. This study reveals compositional and functional imbalances in the GM of nAMD patients compared to healthy controls. Furthermore micronutrient supplementation demonstrated a potential to restore the gut-retina axis, suggesting its therapeutic efficacy in improving ocular outcomes in nAMD patients. These findings underscore the intricate interplay between the GM and ocular health, offering insights into innovative interventions for AMD management

Read the detailed description

Age-related macular degeneration (AMD) stands as the primary cause of visual impairment in the over-65-year-old population of industrialized countries, affecting approximately 170 million people worldwide . AMD is a multifactorial disease in the pathogenesis of which, that it's not yet fully understood, genetic and environmental factors are involved. Specifically, there are two main types of AMD, both culminating in central vision deficiency and potential blindness due to the death of photoreceptors. The first type of AMD type, known as dry AMD, is characterized by the accumulation of extracellular material (i.e. lipids, vitronectin, inflammatory or amyloid proteins) between the Bruch's membrane and the retinal pigment epithelium, leading to the formation of drusen. Drusen are small yellow or white spots on the retina that can gradually evolve either into retinal and pigment epithelium atrophy or, for approximately 20% of patients, progress into the second AMD type that is called wet AMD or neovascular AMD (nAMD). nAMD is distinguished by the development of new choroidal vessels, a condition that can result in permanent visual impairment. Presently, although therapeutic options for dry AMD are limited, nAMD is treated with intravitreal injections of anti-VEGF (vascular endothelial growth factor) drugs, which have proven effective in slowing angiogenic development and limiting the progression of nAMD. Moreover, recent investigations have implicated immune system alterations, oxidative stress, and overweight as critical factors in AMD pathogenesis. Particularly, many studies have recently highlighted the potential benefits of dietary supplementation with micronutrients having antioxidant and antiinflammatory effects in reducing the risk of AMD development. Notably, the AREDS2 study definitively demonstrated the efficacy of dietary supplementation with lutein and zeaxanthin in reducing the risk of progression of early-stage AMD. In detail, the administration of lutein and zeaxanthin, which can absorb blue light and neutralize free radicals and reactive oxygen species in the macula, has been associated with increased macular pigment optical density (MPOD), improved visual acuity and a reduced risk of retinal aging. Moreover, other micronutrients such as vitamins E and C can prevent the progression of maculopathy by providing protection against oxidative stress and maintaining GM homeostasis while oral zinc supplementation can reduce the complement-mediated inflammation in the retinal pigment epithelium, which plays a fundamental role in the etiology of AMD. Additionally, saffron (Crocus sativus), which contains active components such as crocin, safranal, crocetin, and picrocrocin, has demonstrated antioxidant and anti-inflammatory effects, leading to significant improvements in the retinal function of AMD patients. Furthermore, considering that the retina is an extension of the brain both anatomically and developmentally, the hypothesis of a gut-retina interplay has been recently proposed, paralleling the widely explored bidirectional communication between the gut and the brain. Objectives of the study To evaluate the GM composition and function of nAMD patients in comparison to healthy subjects and considering the dual potential of micronutrients to act through direct antioxidant mechanisms and modulation of the GM, the investigators assessed the impact of a novel micronutrient supplementation based on lutein, zeaxanthin and saffron on ophthalmological parameters and microbial features of nAMD patients.

Being tested
a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg), anti-VEGF treatment
Keywords
Age-related macular degeneration, Gut microbiota, Gut-retina axis, Micronutrient, Short chain fatty acids
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg)Dietary supplement

    Also called Drusen off

    In this three-arm randomized, controlled trial, with one arm represented by healthy subjects, eligible participants were randomly divided into two groups. Fifteen patients were randomly allocated to the intervention group and received, for 6 months, intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen and daily supplementation with a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg). The other fifteen patients was assigned to the control group and only received the intravitreal anti-VEGF treatment at a fixed regimen for 6 months

  • anti-VEGF treatmentDrug

    Intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen for six months

Study groups in NCT06391411
Study groupRoleWhat they receive
ControlNo interventionHealthy controls received no intervention
Micronutrient supplementation+ Aflibercept 2 mg, 0.05 mlExperimentalPatients received intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen and daily supplementation with a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) for 6 months
Receives: Dietary Supplement: a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg); Drug: anti-VEGF treatment
Aflibercept 2 mg, 0.05 mlActive comparatorPatients received only intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) for 6 months
Receives: Drug: anti-VEGF treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in gut microbiota composition

    Changes in gut microbiota composition assessed by 16S sequencing

    Measured: At baseline and at month 6

  2. Changes in gut microbiota function

    Changes in gut microbiota function (quantification of short-, medium- and long-chain fatty acids)assessed with gas chromatography-mass spectrometry

    Measured: At baseline and at month 6

  3. Ophthalmological examination

    Ophthalmological examination with best correct visual acuity (BCVA), biomicroscopy and swept optical coherence tomography (OCT)

    Measured: At baseline and at month 6

Secondary outcomes (11)

  1. White blood cells

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  2. Red blood cells

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  3. Hemoglobin

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  4. Platelets

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  5. Glucose

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  6. HDL-cholesterol

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  7. LDL-cholesterol

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  8. Triglycerides

    Quantification with standard laboratory procedures

    Measured: At baseline and at month 6

  9. Evaluation of Interleukin-6

    Measured: At baseline and at month 6

  10. Evaluation of Interleukin-10

    Measured: At baseline and at month 6

  11. Evaluation of tumor necrosis factor-α (TNF-α)

    Measured: At baseline and at month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2024
  2. Study start1 Mar 2021
  3. Primary completion1 Mar 2022
  4. Study completion1 May 2024

Resources

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
Model description
Randomized controlled trial
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06391411
Sponsor's protocol ID
Drusen off
Status last verified
Jul 2024
First submitted
16 Apr 2024
Last updated
31 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016 Dec 22;3:34. doi: 10.1186/s40662-016-0063-5. eCollection 2016.

    PubMed 28032115

  • Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J; Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch Ophthalmol. 2009 Apr;127(4):533-40. doi: 10.1001/archophthalmol.2009.58.

    PubMed 19365036

  • Chapman NA, Jacobs RJ, Braakhuis AJ. Role of diet and food intake in age-related macular degeneration: a systematic review. Clin Exp Ophthalmol. 2019 Jan;47(1):106-127. doi: 10.1111/ceo.13343. Epub 2018 Jul 10.

    PubMed 29927057

  • Rinninella E, Mele MC, Merendino N, Cintoni M, Anselmi G, Caporossi A, Gasbarrini A, Minnella AM. The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut(-)Retina Axis. Nutrients. 2018 Nov 5;10(11):1677. doi: 10.3390/nu10111677.

    PubMed 30400586

  • Zhang QY, Tie LJ, Wu SS, Lv PL, Huang HW, Wang WQ, Wang H, Ma L. Overweight, Obesity, and Risk of Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1276-83. doi: 10.1167/iovs.15-18637.

    PubMed 26990164

  • Age-Related Eye Disease Study 2 (AREDS2) Research Group; Chew EY, Clemons TE, Sangiovanni JP, Danis RP, Ferris FL 3rd, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Chandra SR, Blodi BA, Domalpally A, Friberg T, Wong WT, Rosenfeld PJ, Agron E, Toth CA, Bernstein PS, Sperduto RD. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014 Feb;132(2):142-9. doi: 10.1001/jamaophthalmol.2013.7376.

    PubMed 24310343

  • Zeng S, Hernandez J, Mullins RF. Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration. Invest Ophthalmol Vis Sci. 2012 Feb 27;53(2):1041-7. doi: 10.1167/iovs.11-8531. Print 2012 Feb.

    PubMed 22247465

Questions about this trial

What is this clinical trial studying?

A study testing a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) and anti-VEGF treatment in people with Age-Related Macular Degeneration, run by Azienda Ospedaliero-Universitaria Careggi at 1 site in Italy.

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 3 inclusion and 3 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 31 Jul 2024. 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 Italy. 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. 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?

Changes in gut microbiota composition (time frame: At baseline and at month 6). The study lists 3 primary outcomes in all. 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 NCT06391411, which also lists 7 linked publications.

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 31 Jul 2024.

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