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

NCT06391411 | Completed

• 1 other identifier: Drusen off
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Age-Related Macular Degeneration

Keywords

Age-related macular degeneration; Gut microbiota; Gut-retina axis; Micronutrient; Short chain fatty acids

Outcome Measures

Primary Outcomes (3)

• Changes in gut microbiota composition

  Changes in gut microbiota composition assessed by 16S sequencing

  At baseline and at month 6

• 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

  At baseline and at month 6

• Ophthalmological examination

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

  At baseline and at month 6

Secondary Outcomes (11)

• White blood cells

  At baseline and at month 6

• Red blood cells

  At baseline and at month 6

• Hemoglobin

  At baseline and at month 6

• Platelets

  At baseline and at month 6

• Glucose

  At baseline and at month 6

Study Arms (3)

Control

NO INTERVENTION

Healthy controls received no intervention

Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml

EXPERIMENTAL

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

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 ml

ACTIVE COMPARATOR

Patients received only intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) for 6 months

Drug: anti-VEGF treatment

Interventions

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

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

Also known as: Drusen off

Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml

anti-VEGF treatment DRUG

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

Aflibercept 2 mg, 0.05 ml; Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead
• Azienda USL Toscana Centro: collaborator

Study Sites (1)

Unit of Clinical Nutrition, University Hospital of Careggi

Florence, 50134, Italy

Location

Related Publications (7)

• 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.

  PMID: 28032115 RESULT

• 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.

  PMID: 19365036 RESULT

• 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.

  PMID: 29927057 RESULT

• 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.

  PMID: 30400586 RESULT

• 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.

  PMID: 26990164 RESULT

• 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.

  PMID: 24310343 RESULT

• 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.

  PMID: 22247465 RESULT

MeSH Terms

Conditions

Macular Degeneration

Interventions

Zeaxanthins; Ascorbic Acid; Vitamin E; Zinc

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Xanthophylls; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Nutrition

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 30, 2024
• Study Start: March 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: May 1, 2024
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)