Effect of Two Probiotic Formulations on Mental Health and Mood Biomarkers in Adults With Depressive Symptoms

Effect of Two Probiotic Formulations on Mental Health and Mood Biomarkers in Adults With Depressive Symptoms: A Pilot Randomized Placebo-controlled Trial

This is a 3-arm, parallel-group, randomized, double-blind, placebo-controlled pilot trial. Sixty adults presenting with depressive symptoms will be randomly allocated to one of 3 groups comprising (1) Bifidobacterium adolescentis or (2) Lactocaseibacillus rhamnosus LGG and Bifidobacterium BB-12 or (3) a placebo for 12 weeks.

At baseline (Visit 2), midpoint (Visit 3) and end-of-study (Visit 4) visits, participants meeting eligibility criteria will complete the BDI-II, BAI, DASS-21 and PROMIS Sleep questionnaires and blood samples will be collected for biomarker assessments. Fecal samples will be collected prior to the baseline and end-of-study visits for microbial profiling.

Study Overview

• Status: Completed
• Conditions: Depression, Anxiety
• Intervention / Treatment: Dietary supplement: B. adolescentis Bif-038; Dietary supplement: Lacticaseibacillus rhamnosus, LGG® and Bifidobacterium, BB-12®; Dietary supplement: Placebo

Detailed Description

This is a 3-arm, parallel-group, randomized, double-blind, placebo-controlled pilot trial. Sixty adults presenting with depressive symptoms will be randomly allocated to one of 3 groups comprising (1) Bifidobacterium adolescentis or (2) Lactocaseibacillus rhamnosus LGG and Bifidobacterium BB-12 or (3) a placebo for 12 weeks.

At screening (Visit 1), the study design will be explained to participants, following which signed GDPR and study informed consent will be obtained. Participants will be assessed for eligibility, medical history and concomitant therapies.

At baseline (Visit 2), midpoint (Visit 3) and end-of-study (Visit 4) visits, participants meeting eligibility criteria will complete the BDI-II, BAI, DASS-21 and PROMIS Sleep questionnaires and blood samples will be collected for biomarker assessments. Fecal samples will be collected prior to the baseline and end-of-study visits for microbial profiling.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Duncraig, Western Australia, Australia, 6023
      • Clinical Research Australia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Generally healthy adults (male and female) 18 to 65 years
2. Currently experiencing depressive symptoms as indicated by a score of between 20 and 40 on the BDI-II at both the screening and baseline visit
3. Body mass index (BMI) between 18.5 and 30.0 kg/m2
4. Non-smoker
5. No plan to change dietary or exercise habits during the study period
6. No recent history (within 3 months) or plan to commence new treatments over the study period
7. Willing and able to take probiotic/placebo regimen for 12 weeks
8. Understand, willing and able to comply with all study procedures
9. Willing to provide a personally signed and dated informed consent form detailing all pertinent aspects of the trial.

Exclusion Criteria:

1. Suffering from recently diagnosed or unmanaged medical conditions including but not limited to: diabetes, hyper/hypotension, cardiovascular disease, a gastrointestinal disease requiring regular use of medications, gallbladder disease, autoimmune disease, endocrine disease, acute or chronic pain condition, or cancer/malignancy
2. Diagnosis of psychiatric or neurological conditions including but not limited to: psychiatric disorders other than mild-to-moderate depression and/or anxiety disorder, or neurological disease (e.g., Parkinson's, Alzheimer's disease, intracranial hemorrhage, head or brain injury)
3. Regular medication intake, including but not limited to anticholinergics, anti-epileptics, acetylcholinesterase inhibitors, benzodiazepines, antipsychotics, opioids, or corticosteroids.
4. Within 2 months before screening, the use of pharmaceutical medications, including but not limited to immunosuppressant drugs, antibiotics, and steroids
5. Change in medication (dose or type) in the last 3 months or an expectation to change during the study duration. Permitted medications include, but are not limited to, pharmaceutical antidepressants such as selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs), cholesterol-lowering medications, antihypertensives, proton pump inhibitors, and thyroid medications,
6. Use of probiotics or mood support supplement up to 4 weeks before study commencement
7. Current or 12-month history of illicit drug abuse
8. Alcohol intake greater than 14 standard drinks per week
9. Any significant surgeries over the last year
10. Women who are pregnant, breastfeeding or intend to fall pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsule	Dietary supplement: Placebo; Placebo capsule delivered orally once daily
Experimental: B. adolescentis Bif-038; Probiotic capsule (single strain)	Dietary supplement: B. adolescentis Bif-038; B. adolescentis Bif-038 (probiotic capsule) delivered orally once daily at a minimum of 5 billion CFU/day
Experimental: Lacticaseibacillus rhamnosus, LGG® and Bifidobacterium, BB-12®; Probiotic capsule (combination strain)	Dietary supplement: Lacticaseibacillus rhamnosus, LGG® and Bifidobacterium, BB-12®; Lacticaseibacillus rhamnosus, LGG® and Bifidobacterium, BB-12® (probiotic capsule) delivered orally once daily at a minimum of 1 billion CFU/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory-II (BDI-II) score	Change in BDI-II score after 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Anxiety Inventory (BAI) score	Change in BAI score	12 weeks
Depression, Anxiety, Stress Scale (DASS-21) total score	Change in DASS-21 total score	12 weeks
DASS-21 Stress score	Change in DASS-21 Stress score	12 weeks
DASS-21 Depression score	Change in DASS-21 Depression score	12 weeks
DASS-21 Anxiety score	Change in DASS-21 Anxiety score	12 weeks
Brain-derived neurotrophic factor blood concentration	Change in brain-derived neurotrophic factor blood concentration	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Sleep Disturbance and Sleep-Related Impairment Scale score	Change in PROMIS Sleep Disturbance and Sleep-Related Impairment Scale score	12 weeks
Tumor necrosis factor-alpha blood concentration	Change in tumor necrosis factor-alpha blood concentration	12 weeks
Interleukin-6 blood concentration	Change in interleukin-6 blood concentration	12 weeks
Interleukin-1beta blood concentration	Change in interleukin-1beta blood concentration	12 weeks
High sensitivity C-reactive protein blood concentration	Change in high sensitivity C-reactive protein blood concentration	12 weeks
Interferon-gamma blood concentration	Change in interferon-gamma blood concentration	12 weeks
Lipopolysaccharide-binding protein blood concentration	Change in lipopolysaccharide-binding protein blood concentration	12 weeks
Intestinal fatty acid-binding protein blood concentration	Change in intestinal fatty acid-binding protein blood concentration	12 weeks
Blood cortisol concentration	Change in blood cortisol concentration	12 weeks
Hair cortisol concentration	Change in hair cortisol concentration	12 weeks
Heart rate variability	Change in heart rate variability via electrocardiogram (ECG) measurements	12 weeks
Fecal microbial profile	Change in fecal microbial profile via shotgun metagenomic sequencing	12 weeks

Collaborators and Investigators

• Sponsor: Chr Hansen
• Investigators: Principal Investigator: Adrian Lopresti, PhD, Clinical Research Australia

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: HND-MH-051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No