NCT07497347

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
84

participants targeted

Target at P50-P75 for not_applicable

Timeline
32mo left

Started Mar 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress10%
Mar 2026Feb 2029

First Submitted

Initial submission to the registry

February 9, 2026

Completed
20 days until next milestone

Study Start

First participant enrolled

March 1, 2026

Completed
26 days until next milestone

First Posted

Study publicly available on registry

March 27, 2026

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2028

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2029

Last Updated

March 27, 2026

Status Verified

March 1, 2026

Enrollment Period

2.3 years

First QC Date

February 9, 2026

Last Update Submit

March 24, 2026

Conditions

Late-Life Depression

Keywords

Late-life depressionL-serine supplementationAgeing- related Cognitive Decline

Outcome Measures

Primary Outcomes (5)

  • 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.

    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.

    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.

    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

    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.

    Baseline, Week 18, Week 48 (end of trial)

Secondary Outcomes (6)

  • Electroencephalogram -derived neurophysiological metrics

    Baseline, Week 48 (end of the trial)

  • Gut Microbiome Composition

    Baseline, Week 18; Week 48 (end of trial)

  • Immune-related biomarkers levels

    Baseline; Week 18; Week 48 (end of trial)

  • Amino acid and metabolic biomarkers

    Baseline, Week 18; Week 48 (end of trial)

  • Neuroendocrine and stress-related biomarkers

    Baseline, Week 18; Week 48

  • +1 more secondary outcomes

Study Arms (2)

L-serine group

EXPERIMENTAL

L-serine supplementation, 6 g/day, oral stick, 48 weeks.

Dietary Supplement: L-serine supplementation

Placebo group

PLACEBO COMPARATOR

Maltodextrine supplementation, 6 g/day, oral stick, 48 weeks.

Other: Placebo

Interventions

L-serine supplementationDIETARY_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.

L-serine group
PlaceboOTHER

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.

Placebo group

Eligibility Criteria

Age65 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

RECRUITING

Central Study Contacts

Moira Marizzoni, PhD

CONTACT

(+39) 030 35 01 563mmarizzoni@fatebenefratelli.eu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Model Details: Two-arm randomized controlled design
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 9, 2026

First Posted

March 27, 2026

Study Start

March 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

February 1, 2029

Last Updated

March 27, 2026

Record last verified: 2026-03

Locations

IT(1)