The goal of this clinical trial is to look at the efficacy and safety of giving oral serine (an amino acid) on the progression of structural and functional changes of the retina in people with MacTel type 2. The main questions it aims to answer are: * Does serine slow the progression of MacTel? * Is long-term serine supplementation safe in people with MacTel? Researchers will compare serine to a placebo (a look-alike substance that contains no drug) to see if serine works to slow the progression of MacTel. Participants will: * Take serine or a placebo twice a day for 24 months * Visit the clinic once every 6 months for eye exam, eye imaging and blood tests * Keep a diary of their symptoms, missed doses, and changes in medications
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Hamilton Glaucoma Center- UCSD
La Jolla, California, United States
University of Michigan, Kellogg Eye Center
Ann Arbor, Michigan, United States
Retina Associates Of Cleveland, Inc.
Cleveland, Ohio, United States
University of Utah Health Care, Moran Eye Center
Salt Lake City, Utah, United States
Save Sight Institute
Sydney, New South Wales, Australia
Cerulea- RVEEH
Melbourne, Victoria, Australia
University of Bonn
Bonn, Germany
University of Freiburg, Department of Ophthalmology
Freiburg im Breisgau, Germany
St. Franziskus Hospital
Münster, Germany
Radboud University Medical Center
Nijmegen, Netherlands
...and 2 more locations
EZ loss
Mean rate of change in the total area of EZ loss (IS/OS; macular photoreceptor loss) from Baseline (BL) through Month 24 (M24), as assessed using SD-OCT in the study eye(s).
Time frame: Baseline through Month 24
EZ loss at different time points
Mean rate of change in the area of EZ loss (IS/OS; macular photoreceptor loss) from BL through Month 12 (M12) in the study eye(s) and through M12 and M24 in the fellow eye, as assessed using SD-OCT
Time frame: Baseline through Month 12 and 24
Changes in Disease Severity
Changes in disease severity (stages, according to Chew et al) in study eye(s), and fellow eye, from BL to M24
Time frame: Baseline through Month 24
Retinal Sensitivity Loss
Mean change in retinal sensitivity loss as measured by Macular Integrity Assessment (MAIA) from BL to M24 in study eye(s), and fellow eye
Time frame: Baseline through Month 24
Reading Speed
Mean change in monocular and binocular reading speed assessed using International Reading Speed Texts (IReST) cards from BL through M24 in the study eye(s), and fellow eye
Time frame: Baseline through Month 24
Contrast Sensitivity
Mean change in monocular contrast sensitivity from BL to M24 in the study eye(s) and fellow eye as assessed by Pelli-Robson contrast sensitivity charts
Time frame: Baseline through Month 24
Low Luminance Visual Acuity
Mean change in monocular low luminance visual acuity (LLVA) scores from BL to M24 in the study eye(s) and fellow eye as assessed by ETDRS charts
Time frame: Baseline through Month 24
Low Luminance Deficit
Mean change in low luminance deficit (LLVA - BCVA) from BL to M24 in the study eye(s) and fellow eye
Time frame: Baseline through Month 24
Best Corrected Visual Acuity
Mean change in monocular best-corrected visual acuity (BCVA) scores from BL to M24 in the study eye(s) and fellow eye as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) charts
Time frame: Baseline through Month 24
Corneal Nerve fiber Density
Mean change in corneal nerve fiber and branch density (biomarkers of peripheral nerve health) from BL to M6, M12, M18 and M24 in the study eye(s) and fellow eye
Time frame: Baseline through Month 6, 12, 18 and 24
HbA1c
Mean change in HbA1c from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
BMI
Mean change in BMI (weight and height will be combined to report BMI in kg/m\^2) from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
Serum Metabolites
Mean changes in fasted serum metabolite values from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
MacTel Metabolic Signature
Mean changes in composite serum metabolic score measuring the global "MacTel Metabolic signature" from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
NEI VFQ-25
Mean change in NEI VFQ-25 scores from BL to M12 and M24
Time frame: Baseline through Month 12 and 24
VILL-33
Mean change in VILL-33 scores from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
TEAEs and SAEs
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and ocular TEAEs and SAEs
Time frame: Baseline through Month 24
ETDRS Letter Score
Number of study eyes, fellow eyes with \>= 15 letter loss (ETDRS letter score), \>= 10 letter loss and \>= 5 letter loss from BL to M24
Time frame: Baseline through Month 24
Neovascularization
Total number of study eyes, fellow eyes showing a de novo development of neovascularization from BL to M24
Time frame: Baseline through Month 24
Outer Retinal Hyper-Reflectivity
Total number of study eyes, fellow eyes showing a de novo development of outer retinal hyper-reflectivity from BL to M24
Time frame: Baseline through Month 24
Hip to waist ratio
Mean change in hip-to-waist ratio from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
Lipid Levels
Mean change in Lipid Levels from BL to M12 and M24
Time frame: Baseline through Months 12 and 24
Corneal Nerve Fiber Length
Mean change in corneal nerve fiber length (biomarker of peripheral nerve health) from BL to M6, M12, M18 and M24 in the study eye(s) and fellow eye
Time frame: Baseline through Months 6, 12, 18 and 24
Corneal Nerve Fiber Tortuosity
Mean change in corneal nerve fiber tortuosity (biomarker of peripheral nerve health) from BL to M6, M12, M18 and M24 in the study eye(s) and fellow eye
Time frame: Baseline through Months 6, 12, 18 and 24
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.