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

March 24, 2026 updated by: IRCCS Centro San Giovanni di Dio Fatebenefratelli

Translational Investigation of Specific Amino Acid Supplementation and Lifestyle Factors in 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Brescia, Italy, 25125
        • Recruiting
        • IRCCS Centro San Giovanni di Dio Fatebenefratelli
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: L-serine group
L-serine supplementation, 6 g/day, oral stick, 48 weeks.
Dietary supplement: 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 Comparator: Placebo group
Maltodextrine supplementation, 6 g/day, oral stick, 48 weeks.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline; week 18; week 48 (end of the trial)
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.
Baseline, Week 18; Week 48 (end of the trial)
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.
Baseline; Week 18; Week 48 (end of the trial)
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
Baseline, Week 18; Week 48 (end of the trial)
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.
Baseline, Week 18, Week 48 (end of trial)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 48 (end of the trial)
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.
Baseline, Week 18; Week 48 (end of trial)
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.
Baseline; Week 18; Week 48 (end of trial)
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.
Baseline, Week 18; Week 48 (end of trial)
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.
Baseline, Week 18; Week 48
Neurotrophic biomarkers
Time Frame: Baseline, Week 18; Week 48
Changes in brain-derived neurotrophic factor (BDNF) levels will be measured in blood samples
Baseline, Week 18; Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

February 9, 2026

First Submitted That Met QC Criteria

March 24, 2026

First Posted (Actual)

March 27, 2026

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CERP-2024-23685719

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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