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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:
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-serine group | Experimental | L-serine supplementation, 6 g/day, oral stick, 48 weeks. |
|
| Placebo group | Placebo Comparator | Maltodextrine supplementation, 6 g/day, oral stick, 48 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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-Ã…sberg Depression Rating Scale | The Montgomery-Ã…sberg 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Electroencephalogram -derived neurophysiological metrics | Electroencephalogram (EEG) recordings will be used to derive individual spectral analysis and connectivity. | Baseline, Week 48 (end of the trial) |
| Gut Microbiome Composition |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Moira Marizzoni, PhD | Contact | (+39) 030 35 01 563 | mmarizzoni@fatebenefratelli.eu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IRCCS Centro San Giovanni di Dio Fatebenefratelli | Recruiting | Brescia | 25125 | Italy |
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Two-arm randomized controlled design
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| 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. |
|
| 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 | 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 | 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 | 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 | Changes in brain-derived neurotrophic factor (BDNF) levels will be measured in blood samples | Baseline, Week 18; Week 48 |