Macular telangiectasia type 2 (MacTel) is a bilateral, slowly progressive retinal neurodegenerative disease characterized by photoreceptor loss, vascular abnormalities, and gradual decline in visual function.
Alterations in serine metabolism and the accumulation of toxic deoxysphingolipids have been implicated in the pathophysiology of MacTel. Oral serine supplementation has been proposed as a potential approach to modify this metabolic pathway and reduce the formation of potentially neurotoxic metabolites.
This study is a randomized, double-masked, placebo-controlled, parallel-group clinical trial designed to evaluate the effect of oral serine supplementation on disease progression in participants with macular telangiectasia type 2.
Participants will undergo a screening evaluation to determine eligibility. Eligible participants will be adults aged 18 years or older with a confirmed diagnosis of MacTel through the Natural History Observation Registry (NHOR) study. Participants must meet all eligibility criteria. Eligibility and assignment of the study eye will be determined by review of the images taken at screening. If both eyes are eligible, both eyes may be included as study eyes. A minimum of 110 participants will complete the study.
At the baseline visit, participants will be randomized in a 1:1 ratio to receive either oral serine or placebo. Randomization will be stratified by diabetes status to ensure balanced distribution of participants with and without type 2 diabetes between treatment groups. Participants, investigators, study staff, and outcome assessors will remain masked to treatment assignment throughout the study.
Participants will receive their assigned study treatment for 24 months. In-person study visits will occur every 6 months, with telephone contacts between visits to assess treatment compliance and adverse events. Retinal structure, visual function, and participant safety will be monitored throughout the 24-month treatment period. A follow-up telephone contact will occur approximately 4 weeks after discontinuation of study treatment.
Data will be collected on both eyes of each participant; however, only eyes designated as study eyes and meeting eligibility criteria will be included in the primary efficacy analysis.
The primary objective of the study is to evaluate the effect of serine supplementation compared with placebo on the progression of photoreceptor loss in MacTel. Secondary objectives include the effect of serine supplementation on further structural retinal changes and visual function as well as the assessment of safety and tolerability of long-term oral serine supplementation in this population.
