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NCT Number: NCT07497347

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

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.

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Key information

Conditions

Late-Life Depression

Age range

65 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location status: Recruiting

Location contact

Annamaria Cattaneo, PhD

CONTACT

[email protected]

0303501598

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 65-85 years;
  • Presence of depressive symptoms, defined as a score ≥ 5 on the Geriatric Depression Scale-15 items (GDS-15) or ≥ 5 on the Patient Health Questionnaire-9 (PHQ-9).

Exclusion criteria

  • Diagnosis of dementia;
  • Use of antibiotics or anti-inflammatory medications within the previous 8 weeks;
  • Active gastrointestinal disease;
  • Severe chronic medical conditions (e.g., advanced-stage cancer, severe cardiac or renal disorders, or other debilitating diseases);
  • Renal dysfunction;
  • Current alcohol or substance abuse;
  • Major surgical procedures within the previous 6 months.

Treatment and study plan

L-serine supplementation

Dietary Supplement

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

Other

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.

Primary outcomes

  1. Geriatric Depression Scale - 15

    Time frame: 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.

  2. Repeatable Battery for the Assessment of Neuropsychological Status

    Time frame: 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.

  3. Patient Health Questionnaire - 9

    Time frame: 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.

  4. Montgomery-Åsberg Depression Rating Scale

    Time frame: 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

  5. World Health Organization Quality of Life - Bref

    Time frame: 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.

Secondary outcomes

  1. Electroencephalogram -derived neurophysiological metrics

    Time frame: Baseline, Week 48 (end of the trial)

    Electroencephalogram (EEG) recordings will be used to derive individual spectral analysis and connectivity.

  2. Gut Microbiome Composition

    Time frame: Baseline, Week 18; Week 48 (end of trial)

    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.

  3. Immune-related biomarkers levels

    Time frame: Baseline; Week 18; Week 48 (end of trial)

    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.

  4. Amino acid and metabolic biomarkers

    Time frame: Baseline, Week 18; Week 48 (end of trial)

    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.

  5. Neuroendocrine and stress-related biomarkers

    Time frame: Baseline, Week 18; Week 48

    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.

  6. Neurotrophic biomarkers

    Time frame: Baseline, Week 18; Week 48

    Changes in brain-derived neurotrophic factor (BDNF) levels will be measured in blood samples

Study contacts

Contact information is provided by the study sponsor or research team.

Moira Marizzoni, PhD

CONTACT

[email protected]

(+39) 030 35 01 563

Sponsors and collaborators

Lead sponsor

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Other

Registry information

Official study title

Translational Investigation of Specific Amino Acid Supplementation and Lifestyle Factors in Brain Ageing

Acronym: AAAgeing

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Mar 27, 2026
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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