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

Age-Related Macular Degeneration Clinical Trial

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"

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06391411
• Other study ID #: Drusen off
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: May 1, 2024

Study information

• Verified date: April 2024
• Source: Azienda Ospedaliero-Universitaria Careggi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: May 1, 2024
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Macular Degeneration

Intervention

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)
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

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

Locations

Country	Name	City	State
Italy	Unit of Clinical Nutrition, University Hospital of Careggi	Florence

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Careggi	Azienda USL Toscana Centro

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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 — View Citation

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. — View Citation

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. — View Citation

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( — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in gut microbiota composition	Changes in gut microbiota composition assessed by 16S sequencing	At baseline and at month 6
Primary	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
Primary	Ophthalmological examination	Ophthalmological examination with best correct visual acuity (BCVA), biomicroscopy and swept optical coherence tomography (OCT)	At baseline and at month 6
Secondary	White blood cells	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Red blood cells	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Hemoglobin	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Platelets	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Glucose	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	HDL-cholesterol	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	LDL-cholesterol	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Triglycerides	Quantification with standard laboratory procedures	At baseline and at month 6
Secondary	Evaluation of Interleukin-6		At baseline and at month 6
Secondary	Evaluation of Interleukin-10		At baseline and at month 6
Secondary	Evaluation of tumor necrosis factor-a (TNF-a)		At baseline and at month 6