The Role of the Gut Metagenome on the Development of Age Related Macular Degeneration (AMD)

The primary objective of this study is to assess whether compositional and functional alterations of the gut metagenome may be related to AMD. The primary variable for this assessment is the composition of the gut metagenome which will be analyzed by shotgun sequencing to characterize the faecal metagenome. The secondary endpoint is to assess whether single nucleotide polymorphisms in CFH, ARMS2, C3, PLEKHA1, HTRA-1, VEGF-A, VEGF-B, VEGFR and APOE genes which have been shown to be risk factors for the development of AMD and other macular diseases correlate with alterations in the gut metagenome .

Study Overview

• Status: Active, not recruiting
• Conditions: Age Related Macular Degeneration
• Intervention / Treatment: Genetic: metagenome

Detailed Description

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. Despite major research efforts in the last decades the etiology of AMD remains largely undefined and therefore treatment options are only very limited. However, there is evidence that nutrition and inflammation play a role in the pathogenesis of AMD . The latter is also corroborated by the finding that single nucleotide polymorphism in the gene encoding complement factor H is associated with AMD . In addition to CHF other genes such as ARMS2, C3, PLEKHA1, HTRA-1, VEGF-A, VEGF-B, VEGFR and APOE have been associated with development of AMD. Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation . Gut bacteria use mostly fermentation to generate energy, converting sugars, in part, to short-chain fatty acid, that are used by the host as energy source. Beyond short-chain fatty acids gut bacteria can provide some amino acids and contribute certain vitamins such as biotin to the host . The investigators propose to investigate whether compositional and functional alterations of the gut microbiota are a risk factor for developing AMD.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern, Department of Ophthalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients with age related macular degeneration (AMD)

Description

Inclusion criteria:

• Subject must be willing to give written informed consent and willing to provide blood and stool probes
• Patients with clinically confirmed AMD 18 years of age or greater
• Probands with no signs of AMD 18 years of age or greater

Exclusion criteria:

• Smoking
• Chronic inflammatory disease (autoimmune diseases such as rheumatoid arthritis, lupus erythematodes, chronic inflammatory bowel disease)
• Diabetes as defined by The World Health Organization (WHO) criteria
• Treated hyperlipidemia
• Obesity with a body mass index (BMI) greater than or equal to 30
• Recent (3 month) history of use of systemic antibiotics
• Opacities of ocular media excluding detailed observation of the retina

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
age related macular degeneration; metagenome AMD	Genetic: metagenome; metagenome
controls; metagenome controls	Genetic: metagenome; metagenome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
taxonomic and functional characterization of gut microbiota	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Gut-microbiota-based AMD classification	3 years
AMD-associated gut microbial markers	3 years

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Study Chair: Martin Zinkernagel, M.D, PhD, Department of Ophthalmology, University Hospital Bern, Switzerland; Principal Investigator: Martin S Zinkernagel, MD, PhD, Department of Ophthalmology, University Hospital Bern, Switzerland; Study Director: Martin Fiedler, MD, University Hospital Bern, Switzerland

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 8, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: KEK BE 205/13, PB_2016-01922