- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06391411
Effect of Micronutrient Supplementation on the Intestinal Microbiota in Patients With Age-related Macular Degeneration - The Gut-Retina-axis Study
April 29, 2024 updated by: Francesco Sofi, Azienda Ospedaliero-Universitaria Careggi
: 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
Study Overview
Status
Active, not recruiting
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
45
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florence, Italy, 50134
- Unit of Clinical Nutrition, University Hospital of Careggi
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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No Intervention: Control
Healthy controls received no intervention
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Experimental: Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml
Patients 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
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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
Other Names:
Intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen for six months
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Active Comparator: Aflibercept 2 mg, 0.05 ml
Patients received only intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) for 6 months
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Intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen for six months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in gut microbiota composition
Time Frame: At baseline and at month 6
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Changes in gut microbiota composition assessed by 16S sequencing
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At baseline and at month 6
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Changes in gut microbiota function
Time Frame: At baseline and at month 6
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Changes in gut microbiota function (quantification of short-, medium- and long-chain fatty acids)assessed with gas chromatography-mass spectrometry
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At baseline and at month 6
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Ophthalmological examination
Time Frame: At baseline and at month 6
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Ophthalmological examination with best correct visual acuity (BCVA), biomicroscopy and swept optical coherence tomography (OCT)
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At baseline and at month 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
White blood cells
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Red blood cells
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Hemoglobin
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Platelets
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Glucose
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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HDL-cholesterol
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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LDL-cholesterol
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Triglycerides
Time Frame: At baseline and at month 6
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Quantification with standard laboratory procedures
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At baseline and at month 6
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Evaluation of Interleukin-6
Time Frame: At baseline and at month 6
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At baseline and at month 6
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Evaluation of Interleukin-10
Time Frame: At baseline and at month 6
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At baseline and at month 6
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Evaluation of tumor necrosis factor-α (TNF-α)
Time Frame: At baseline and at month 6
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At baseline and at month 6
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2021
Primary Completion (Actual)
March 1, 2022
Study Completion (Estimated)
May 1, 2024
Study Registration Dates
First Submitted
April 16, 2024
First Submitted That Met QC Criteria
April 29, 2024
First Posted (Actual)
April 30, 2024
Study Record Updates
Last Update Posted (Actual)
April 30, 2024
Last Update Submitted That Met QC Criteria
April 29, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Drusen off
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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