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

July 30, 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Italy
      • Florence, Italy, 50134
        • Unit of Clinical Nutrition, University Hospital of Careggi

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Control
Healthy controls received no intervention
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
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
Other Names:
  • Drusen off
Drug: anti-VEGF treatment
Intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen for six months
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
Drug: anti-VEGF treatment
Intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen for six months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in gut microbiota composition
Time Frame: At baseline and at month 6
Changes in gut microbiota composition assessed by 16S sequencing
At baseline and at month 6
Changes in gut microbiota function
Time Frame: At baseline and at month 6
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
Time Frame: At baseline and at month 6
Ophthalmological examination with best correct visual acuity (BCVA), biomicroscopy and swept optical coherence tomography (OCT)
At baseline and at month 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
White blood cells
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Red blood cells
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Hemoglobin
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Platelets
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Glucose
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
HDL-cholesterol
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
LDL-cholesterol
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Triglycerides
Time Frame: At baseline and at month 6
Quantification with standard laboratory procedures
At baseline and at month 6
Evaluation of Interleukin-6
Time Frame: At baseline and at month 6
At baseline and at month 6
Evaluation of Interleukin-10
Time Frame: At baseline and at month 6
At baseline and at month 6
Evaluation of tumor necrosis factor-α (TNF-α)
Time Frame: At baseline and at month 6
At baseline and at month 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Ospedaliero-Universitaria Careggi

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Azienda USL Toscana Centro

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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 16, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 30, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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