Late-Life Depression
Conditions
Keywords
Late-life depression, L-serine supplementation, Ageing- related Cognitive Decline
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.
Interventions
DIETARY_SUPPLEMENTL-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.
OTHERPlacebo
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.
Sponsors
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Two-arm randomized controlled design
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electroencephalogram -derived neurophysiological metrics | Baseline, Week 48 (end of the trial) | Electroencephalogram (EEG) recordings will be used to derive individual spectral analysis and connectivity. |
| Gut Microbiome Composition | 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. |
| Immune-related biomarkers levels | 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. |
| Amino acid and metabolic biomarkers | 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. |
| Neuroendocrine and stress-related biomarkers | 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. |
| Neurotrophic biomarkers | Baseline, Week 18; Week 48 | Changes in brain-derived neurotrophic factor (BDNF) levels will be measured in blood samples |
Countries
Italy
Contacts
CONTACTMoira Marizzoni, PhD
Outcome results
None listed