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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Keratoconus

Intervention / Treatment
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* Dietary Supplement: Highly-concentrated DHA triglyceride (Tridocosahexanoin-AOX 70%)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |