Cognition Function, Mild Depression
Conditions
Brief summary
The goal of this clinical trial is to learn if daily single-strain probiotic supplementation (Lactobacillus plantarum) works to improve cognitive function and depressive symptoms in Egyptian women aged 50-64 years with mild depression. It will also learn about its effects on systemic inflammation and autonomic nervous system function via the gut-brain axis The main questions it aims to answer are: Does a 12-week probiotic supplementation improve cognitive function (measured by MoCA-B) compared to a placebo? Does it reduce the severity of depressive symptoms (measured by BDI-II)? Does it reduce systemic inflammation (measured by hs-CRP levels in the blood)? Does it enhance autonomic nervous system function (measured by Heart Rate Variability - HRV via a smartphone app)? Researchers will compare the probiotic capsule (Lactobacillus plantarum, 10 billion CFU) to a placebo (a look-alike capsule containing starch) to see if the probiotic works better than placebo. Participants will: Take one probiotic or placebo capsule orally every morning with breakfast for 12 weeks. Visit the Family Medicine outpatient clinic at baseline and at 12 weeks for cognitive and psychological tests, HRV measurements, and blood tests. Receive weekly follow-up messages on WhatsApp to monitor adherence and report any dietary changes or potential side effects.
Detailed description
Depression poses a significant global public health challenge, with women being two to three times more likely than men to develop the condition. Emerging evidence highlights a bidirectional relationship between depression, cognitive impairment, and the gut microbiota via the gut-brain axis. Dysbiosis in gut microbiota can contribute to systemic inflammation, impaired neurogenesis, and psychiatric disorders. Specific strains such as Lactobacillus plantarum have shown potential in modulating gut-brain communication, reducing inflammation, and improving neurocognitive and psychological outcomes. This triple-blind, randomized, placebo-controlled trial aims to evaluate the efficacy of a 12-week intervention with a single-strain probiotic (Lactobacillus plantarum, 10 billion CFU daily) compared to a placebo in Egyptian women aged 50-64 years presenting with mild depressive symptoms. Study Procedures and Flow: Initial Screening Visit: Potential participants recruited from the Family Medicine outpatient clinics at Kasr Al-Ainy Teaching Hospitals will undergo screening. Eligibility will be confirmed by taking a comprehensive medical/psychiatric history, reviewing concomitant medications/supplements, and evaluating depressive symptoms using the Arabic validated Beck Depression Inventory-II (BDI-II, score 14-19). Eligible participants will provide written informed consent. Baseline Assessment (Week 0): Enrolled participants will undergo baseline evaluations including: Socio-demographic status assessment. Anthropometric measurements (weight, height, BMI). Cognitive assessment using the Arabic version of the Montreal Cognitive Assessment - Basic (MoCA-B). Autonomic nervous system function evaluation via short-term (5-minute) resting Heart Rate Variability (HRV) measured using a smartphone-based photoplethysmography application (Welltory) under standardized conditions. Fasting venous blood sample collection for high-sensitivity C-reactive protein (hs-CRP) level measurement. Randomization and Intervention Phase (Weeks 1-12): Participants will be randomly allocated in a 1:1 ratio to either the probiotic or placebo group using a computer-generated permuted block design. Both intervention (probiotic) and control (placebo) capsules are identical in appearance, size, color, and packaging. Participants, assessors, and the data analyst/statistician will remain blinded throughout the study. Participants will take one capsule daily with breakfast for 12 weeks. Adherence will be monitored through weekly messaging and monthly capsule counts during study visits. Post-Intervention Assessment (Week 12): At the end of the 12-week intervention period, participants will undergo repeat outcome assessments identical to baseline (MoCA-B, BDI-II, HRV, and fasting serum hs-CRP).
Interventions
DIETARY_SUPPLEMENTLactobacillus plantarum
Single-strain probiotic containing Lactobacillus plantarum (approximately 10 billion CFU per capsule). Manufactured by Pescado Pharmaceuticals, Cairo, Egypt. Administered as one capsule daily taken orally with breakfast for 12 weeks.
OTHERplacebo capsule
Placebo capsule containing inert excipients (starch), manufactured by Faculty of Pharmacy, Cairo University. Identical in appearance, size, color, and packaging to the probiotic capsule. Administered as one capsule daily taken orally with breakfast for 12 weeks.
Sponsors
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
"This is a triple-blind trial where participants, assessors/care providers, and the statistician analyzing the dataset are all blinded to group allocation."
Intervention model description
Participants are randomly assigned in a 1:1 ratio to either the probiotic group (Lactobacillus plantarum) or the placebo group for 12 weeks."
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Females, aged 50-64 years * Presence of mild depressive symptoms, defined as a Beck Depression inventory II (BDI-II) total score between 14 and 19 (inclusive) at the screening visit. * Ability to give informed consent
Exclusion criteria
* Moderate and severe depression (BDI-II score \> 19) or active suicidal ideation (assessed by clinical interview). * Diagnosis of bipolar disorder, schizophrenia, or other major psychotic disorder. Current use of antidepressants, antipsychotics, mood stabilizers, or regular anxiolytics * Regular consumption of probiotics, prebiotics, or synbiotic supplements within the past 4 weeks. * Use of antibiotics or antifungals within the past 4weeks. * Known diagnosis of inflammatory bowel disease, celiac disease, or active irritable bowel syndrome with severe symptoms. * History of significant cardiovascular disease (e.g., atrial fibrillation, heart failure, recent MI), uncontrolled hypertension, or type 1 diabetes. * Current use of systemic hormone replacement therapy within the last 3 months.Research Template 6 Final Version: Jan 2024 * Known allergy to any component of the probiotic or placebo. * Severe systemic illness (e.g., uncontrolled diabetes, malignancy, severe hepatic, renal disease or auto-immune diseases). * CRP more than 10
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive function | Baseline and Week 12 | Assessed by change in Montreal Cognitive Assessment Basic (MoCA-B) total score. MoCA-B scores range from 0 to 30, with higher scores indicating better cognitive performance. |
| Change in depressive symptom severity | Baseline and Week 12 | Assessed by change in Beck Depression Inventory-II (BDI-II) total score. BDI-II scores range from 0 to 63, with higher scores indicating higher severity of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum high sensitivity C-reactive protein (hs-CRP) concentration | Baseline and Week 12 | Measured in mg/L using serum samples to evaluate systemic inflammation. |
| Change in heart rate variability (HRV) | Baseline and Week 12 | Assessed via smartphone-based photoplethysmography application (Welltory) to evaluate autonomic nervous system regulation. |
Countries
Egypt
Contacts
CONTACTMarina S Girgis, MD
CONTACTRehab H Mahmoud
Outcome results
None listed