Metabolomics in Surgical Ophthalmological Patients (MISO)

Metabolomics consists in the study of metabolites in body fluids or tissues. It investigates the consequences of the activity of genes and proteins. One of its advantages is that it is able to do a simultaneous measurement of metabolic changes in living organisms as a response to a disturbance (disease, diet, environment, others) and because a metabolic profile is summative of all the biochemical processes occurring in the body at a given time, it makes no presumption about the relative importance of these processes. Ultimately it is a fingerprint of the organism's health status, at a given time.

Metabolomic analysis of serum, plasma and urine has revealed panels of metabolites that distinguish patients with cardiovascular disease, breast cancer, Parkinson disease, Alzheimer's disease and diabetes from control patients. Regarding ocular diseases only few studies have been published, related to diabetic retinopathy, retinal detachment, age-related macular degeneration, uveitis and glaucoma.

Glaucoma is one of the leading causes of blindness in the world, according to the World Health Organization, and there are still no biomarkers that can provide an early diagnosis. Nowadays, glaucoma classification relies substantially in the measurement of intraocular pressure (IOP), which can be rather artificial and also unreliable since IOP values can fluctuate during the day. Moreover, patients with normal IOP values can also develop glaucomatous neuropathy (normal-tension glaucoma, NTG) and progress even when IOP is decreased. Several studies have shown that NTG patients suffer from a systemic vascular dysregulation, with higher rates of systemic hypotension, Raynaud phenomenon and migraine. Hence, other mechanisms than an increased IOP are of importance in the development and progression of glaucoma.

Only one metabolome-wide study has been made in glaucoma (Burgess, I.; 2015). In a sample of 72 american patients with primary open angle glaucoma (POAG), the authors found significant differences in comparison to controls.

The hypothesis for this study is that glaucoma patients will differ from controls, and POAG patients will differ from NTG patients. The investigators will look into metabolomics as a way to create a method to diagnose and stratify patients, as an add-on or alternative to the currently available diagnostic tools like IOP, functional and structural measurement.

Study Overview

• Status: Unknown
• Conditions: Low Tension Glaucoma; Primary Open-angle Glaucoma
• Intervention / Treatment: Diagnostic test: Metabolomics analysis of patient samples

Detailed Description

This is a cross sectional study built to compare samples from glaucoma patients undergoing surgery (open-angle glaucoma and normal-tension glaucoma, age and gender matched) with age and gender-matched controls (healthy patients undergoing cataract surgery). For this the investigators will collect plasma, urine and aqueous humor to be analyzed through mass spectrometry and nuclear magnetic resonance spectroscopy. Patients have a night fasting period prior to sample collection, and a lifestyle and food frequency questionnaire is filled to control for nutritional influence on metabolites. Diabetic patients are excluded, since it would confound our analysis.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven
    • Contact: Sien Boons; Phone Number: 003216340391
    • Sub-Investigator: João Barbosa-Breda, MD
    • Sub-Investigator: Karel Van Keer, MD
    • Sub-Investigator: Uwe Himmelreich, PhD
    • Sub-Investigator: Bart Ghesquière, PhD
    • Sub-Investigator: Anca Croitor Sava, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients from the ophthalmology department that are undergoing intraocular surgery.

Description

Inclusion Criteria:

• glaucoma patients (POAG/NTG): undergoing trabeculectomy, XEN® implantation or cataract surgery
• Controls (non glaucoma): undergoing cataract surgery
• Caucasian

Exclusion Criteria:

• Diabetes mellitus
• any intra ocular surgery on study eye, other than clear cornea cataract surgery more than one year before
• other eye pathologies than the one the surgery is intended for (except refractive error and cataract in glaucoma patients), namely retinopathies, uveitis and other causes for neuropathy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
POAG; Primary open angle glaucoma patients	Diagnostic test: Metabolomics analysis of patient samples; Metabolomics analysis of patient samples by mass spectrometry and nuclear magnetic resonance spectroscopy.
NTG; Normal/Low tension glaucoma patients	Diagnostic test: Metabolomics analysis of patient samples; Metabolomics analysis of patient samples by mass spectrometry and nuclear magnetic resonance spectroscopy.
Control; Patients with cataract and without glaucoma or other eye diseases	Diagnostic test: Metabolomics analysis of patient samples; Metabolomics analysis of patient samples by mass spectrometry and nuclear magnetic resonance spectroscopy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics profile of each group	un-targeted metabolomics and identification of metabolites based on exact mass using metabolomics library	Morning of the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical success of glaucoma patients	Success is defined as an IOP between 6 and 18 mmHg with a reduction of 30% from baseline, and was sub-categorized as complete success if accomplished without glaucoma medication, qualified success with glaucoma medication, and total success as a combination of both complete and qualified. Eyes needing further glaucoma surgery, IOP ≤5 or > 18 mmHg on two consecutive visits, or loss of light perception due to glaucoma were considered as failures. Needling of encysted blebs is not considered a failure.	12 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: FRO (Funds for Research in Ophthalmology, Belgium)

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Anticipated): September 30, 2017
• Study Completion (Anticipated): September 30, 2018

Study Registration Dates

• First Submitted: March 26, 2017
• First Submitted That Met QC Criteria: March 26, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Metabolomics; Glaucoma; Cross sectional studies; Low tension glaucoma; Ophthalmologic surgical procedures
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Optic Nerve Diseases; Glaucoma; Glaucoma, Open-Angle; Low Tension Glaucoma
• Other Study ID Numbers: MISO Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No