An interventional study of L-serine supplementation and Placebo in Late-Life Depression, sponsored by IRCCS Centro San Giovanni di Dio Fatebenefratelli. Recruiting at 1 site in Italy. Open to participants aged 65 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by IRCCS Centro San Giovanni di Dio Fatebenefratelli · Not applicable, Interventional, and Supportive care
The aim of this clinical trial is to investigate the effects of L-serine supplementation on cognitive decline and psychosocial functioning in older adults with late-life depression (LLD). The study will evaluate changes in depressive symptoms, neural and cognitive functioning, and will assess neurophysiological, metagenomic, and biochemical alterations associated with L-serine supplementation compared with placebo.
The main research questions are:
All participants will be assessed at three time points: T0 (baseline, prior to trial initiation), T18 (after 18 weeks), and T48 (after 48 weeks, at the end of the trial).
At each assessment, participants will:
Exclusion Criteria:
L-serine supplementation, 6 g/day, oral stick, 48 weeks.
Dietary Supplement: L-serine supplementation
Maltodextrine supplementation, 6 g/day, oral stick, 48 weeks.
Other: Placebo
Participants randomized to the experimental arm will receive L-serine supplementation (6 g/day), administered orally as a single stick per day for a total duration of 48 weeks.
Participants randomized to the Placebo arm will receive Maltodextrine supplementation (6 g/day), administered orally as a single stick per day for a total duration of 48 weeks.
Geriatric Depression Scale - 15
The Geriatric Depression Scale - 15 items (GDS-15) is a validated clinical instrument widely used in clinical and research settings to screen for depressive symptoms in older adults.
Time frame: Baseline; week 18; week 48 (end of the trial)
Repeatable Battery for the Assessment of Neuropsychological Status
The Repeatable Battery for the Assessment of Neuropsychological (RBANS) is a neuropsychological battery composed of 12 subtests grouped into five domains: Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory. It yields index scores and a total scale score. Higher scores indicate better cognitive functioning, reflecting a more favorable clinical outcome.
Time frame: Baseline, Week 18; Week 48 (end of the trial)
Patient Health Questionnaire - 9
The Patient Health Questionnaire-9 (PHQ-9) is a self-administered instrument used to assess the severity of depressive symptoms based on DSM criteria. It consists of 9 items, each rated from 0 (not at all) to 3 (nearly every day), resulting in a total score ranging from 0 to 27. Higher scores reflect more severe depressive symptoms, indicating a worse clinical outcome.
Time frame: Baseline; Week 18; Week 48 (end of the trial)
Montgomery-Åsberg Depression Rating Scale
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-administered scale designed to assess the severity of depressive symptoms. It consists of 10 items, each rated on a scale from 0 to 6, yielding a total score ranging from 0 to 60. Higher scores indicate greater severity of depression, meaning a worse clinical outcome
Time frame: Baseline, Week 18; Week 48 (end of the trial)
World Health Organization Quality of Life - Bref
The World Health Organization Quality of Life - Bref (WHOQOL-BREF) is a self-report questionnaire developed by the WHO to assess quality of life across multiple domains. It contains 26 items rated on a 5-point Likert scale. Higher scores indicate a better quality of life, reflecting a more favorable outcome.
Time frame: Baseline, Week 18, Week 48 (end of trial)
Electroencephalogram -derived neurophysiological metrics
Electroencephalogram (EEG) recordings will be used to derive individual spectral analysis and connectivity.
Time frame: Baseline, Week 48 (end of the trial)
Gut Microbiome Composition
Assessment of gut microbiome composition through analysis of fecal samples using high-throughput sequencing techniques (e.g., 16S rRNA gene sequencing). Microbial diversity (alpha and beta diversity) and relative abundance of bacterial taxa will be evaluated.
Time frame: Baseline, Week 18; Week 48 (end of trial)
Immune-related biomarkers levels
Plasma and serum levels of immune-related biomarkers will be measured, including cytokines and chemokines, C-reactive protein (CRP), and NLRP3. Quantitative assessment will be performed using validated laboratory assays. Changes in biomarker concentrations over time will be evaluated.
Time frame: Baseline; Week 18; Week 48 (end of trial)
Amino acid and metabolic biomarkers
L-serine and D-serine concentrations will be measured in blood, urine, and fecal samples using validated analytical methods. Quantitative assessment of biomarker levels and changes over time will be performed.
Time frame: Baseline, Week 18; Week 48 (end of trial)
Neuroendocrine and stress-related biomarkers
Cortisol levels will be measured in blood samples and corticosterone levels in fecal samples using validated analytical methods. Quantitative assessment of biomarker concentrations and changes over time will be performed.
Time frame: Baseline, Week 18; Week 48
Neurotrophic biomarkers
Changes in brain-derived neurotrophic factor (BDNF) levels will be measured in blood samples
Time frame: Baseline, Week 18; Week 48
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IRCCS Centro San Giovanni di Dio Fatebenefratelli