Effects of Specific Amino Acid Supplementation and Lifestyle Factors on Brain Ageing

Condition(s) studied

Investigational drug(s) / intervention(s)

L-serine supplementation: 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.

Placebo: 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.

Study summary

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:

* Does L-serine supplementation affect cognitive function, depressive symptoms, and neural functioning in individuals with late-life depression?
* What biological mechanisms may underlie the effects of L-serine on cognitive decline? Participants will be randomly assigned to one of two study arms: an intervention group (total n = 42) receiving L-serine at a dose of 6 g/day for 48 weeks, and a placebo group (total n = 42) receiving 6 g/day of maltodextrin for the same duration.

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:

* complete clinical questionnaires and a neuropsychological assessment;
* provide blood, fecal, and urine samples;
* undergo electroencephalographic (EEG) recordings.

Eligibility

Primary outcome measure(s)

• Geriatric Depression Scale - 15 — Baseline; week 18; week 48 (end of the trial)
  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.
• Repeatable Battery for the Assessment of Neuropsychological Status — Baseline, Week 18; Week 48 (end of the trial)
  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.
• Patient Health Questionnaire - 9 — Baseline; Week 18; Week 48 (end of the trial)
  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.
• Montgomery-Åsberg Depression Rating Scale — Baseline, Week 18; Week 48 (end of the trial)
  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
• World Health Organization Quality of Life - Bref — Baseline, Week 18, Week 48 (end of trial)
  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.

Trial sites (1)

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