Supplementation With a Highly-Concentrated Docosahexaenoic Acid (DHA) Triglyceride in Patients With Keratoconus

Antioxidant and Anti-inflammatory Effects of Oral Supplementation With a Highly-Concentrated Docosahexaenoic Acid (DHA) Triglyceride in Patients With Keratoconus: A Randomized Controlled Preliminary Study

The goal of this randomized controlled preliminary study is to assess the effect of daily supplementation with a nutraceutical formulation of a highly-concentrated DHA triglyceride plus minerals on ophthalmological parameters and biomarkers of oxidative stress and inflammation in blood samples of patients with keratoconus.The main questions it aims to answer are:

• Improvements in ophthalmological parameters.
• Increase in antioxidant capacity, decrease in inflammatory status, and changes in lipidomic biomarkers.

Participants are patients with keratoconus who will be given the nutraceutical supplementation for 3 months.

If there is a comparison group: Researchers will compare patients with keratoconus not given the nutraceutical formulation to see differences in the study variables

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Dietary supplement: Highly-concentrated DHA triglyceride (Tridocosahexanoin-AOX 70%)

Detailed Description

Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, C22:6-n3), a critical component of cell membrane phospholipids, exerts pleiotropic effects at both central and peripheral levels with health benefits in many aspects of neuronal, immune, cognitive, and cardiovascular functions Clinical studies of dietary sup-plementation with a highly-concentrated DHA triglyceride have shown consistent an-ti-inflammatory, antioxidant, antiangiogenic, and antiproliferative effects targeting pathophysiological pathways involved in different eye diseases, including diabetic retinopathy and macular edema, ocular surface disorders, meibomian gland dysfuncton, and pseudoexfoliative glaucoma.

Based on this experience, it was considered of interest to explore the antioxidant and anti-inflammatory potential of a highly-concentrated DHA triglyceride supplement in patients with keratoconus. For this purpose, a prospective preliminary study was designed to assess the effects of 3-month DHA nutritional supplementation on clinical variables, and inflammatory and oxidative stress biomarkers of patients with early and moderate keratoconus.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46015
    • FISABIO Medical Ophthalmology (FOM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of keratoconus stages I to III according to the Amsler-Krumeich classification
• Non-contact lens wearers
• No history of previous corneal surgery
• Capacity to volunteer and willing and able to follow the study protocol

Exclusion Criteria:

• Advanced keratoconus (stage IV of the Amsler-Krumeich classification
• Other ectasias (e.g. iatrogenic secondary to ocular surface surgery with excimer laser, radial keratotomy, traumatic corneal ectasia, etc.)
• Eyelid alterations
• Previous ocular surgery
• Any ocular or systemic condition that may affect the interpretation of results
• Glaucoma or ocular hypertension
• History of ocular trauma, infection or inflammation
• Current treatment with topical or anti-inflammatory drugs
• Use of nutritional supplements including omega-3 fatty acids, vitamins and minerals (unless a washout period of 1 month had been established)
• Hypersensitivity to fish proteins
• Pregnant women
• Refusal to sign the written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DHA group; Supplementation with a highly-concentrated docosahexaenoic acid (DHA) triglyceride (1000 g/day) for 3 months	Dietary supplement: Highly-concentrated DHA triglyceride (Tridocosahexanoin-AOX 70%); Daily administration of 2 capsules of the study product (1000 mg DHA triglyceride) for 3 months
No Intervention: Control group; Routine care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal topography	Changes of ophthalmological parameters	Baseline and after 3 months of supplementation (end of study)
Antioxidant variables	Changes in plasma total antioxidant capacity (TAC), malondialdehyde (MDA) and glutathione (GSH), and GSH/GSSH ratio	Baseline and after 3 months of supplementation (end of study)
Anti-inflammatory variables	cytokine levels IL-1beta, IL-4, IL-6, IL-10, IL-18, TNFalpha, VEGF-A	Baseline and after 3 months of supplementation (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipidomic variables	Serum levels of DHA, arachidonic acid (ARA), n-6 PUFA/n-3 PUFA, omega-3 index	Baseline and after 3 months of supplementation (end of study)

Collaborators and Investigators

• Sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
• Investigators: Principal Investigator: Cristina Peris-Martinez, MD, FISABIO Medical Ophthalmology (FOM)

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: PI_77

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