Clinical trial NCT04125810: A Study to Assess the Safety and Efficacy of Probiotic to Modulate Psychological Stress
Official title: A Randomized, Triple-blind, Placebo-controlled, Parallel-groups Clinical Trial to Assess the Safety and Efficacy of Lactobacillus Paracasei (Lpc-37) to Modulate Psychological Stress
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stress, Psychological
Healthy
Keywords: Probiotic
Stress
Gut-brain axis
Lead sponsor: Danisco
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
name: Daacro
name: 4Pharma Ltd.
First posted: 2019-10-14
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to determine whether Probiotic can modulate the psychological stress experienced by healthy medical, dental and health science students preparing for university/institute of technology semester examination (s), measured by self-report scales and hypothalamic pituitary adrenal axis activity, compared with placebo.

Detailed description: The purpose of this clinical trial is to determine whether Probiotic can modulate the psychological stress experienced by healthy medical, dental and health science students preparing for university/institute of technology semester examination (s), measured by self-report scales and hypothalamic pituitary adrenal axis activity, compared with placebo.

The target group of the proposed study will consist of stress vulnerable / sensitive, healthy male and female adult participants currently enrolled in medical, dental or health science university course that are experiencing psychological stress induced by preparation for university/institute of technology semester examination (s).

Eligibility criteria: Inclusion Criteria:

1. Voluntary, written, informed consent to participate in the study
2. Currently enrolled in medical, dental or health science university/institute of technology course with intention to sit semester examination(s)
3. Male or female aged between 18-40 years (inclusive)
4. Body mass index (BMI) between 18.5 - 29.9 Kg/m2
5. Blood, urine and gastrointestinal safety parameters and blood pressure measurement at baseline indicate they are healthy in the opinion of the Principal Investigator
6. In good general health as estimated by the Principal Investigator, based on medical history (self-reported)
7. Ability of the participant (in the Principal Investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects
8. Ability of the participant (in the Principal Investigator's opinion) to fully comprehend and self-complete all participant reported outcomes (in UK English language)
9. Participant is willing to maintain habitual diet (including caffeine and alcohol), physical activity patterns and smoking habits throughout the intervention period
10. Agreement to comply with the protocol and study restrictions
11. Available for all study visits
12. Females of child-bearing potential required to provide a negative urine pregnancy test and be using effective contraception (e.g. surgically sterilized (tubal ligation or hysterectomy or partner is post-vasectomy, with sterility confirmed) or use an intrauterine device (IUD), a diaphragm or condom combined with contraceptive sponge, foam or jelly, or be using an oral contraceptive for at least 2 cycles before the screening visit (Visit 2). Women who are in same sex relationships or abstaining from sex are not required to take a pregnancy test or be using effective contraception
13. Male participants must agree to use a condom during sexual intercourse from Visit 3 onwards
14. Covered by health insurance system and / or in compliance with the recommendations of National Law in force relating to biomedical research

Exclusion Criteria:

1. Suspected diagnosis of one or more DSM-IV axis 1 disorder(s), including but not limited to: current major depression, anxiety disorder, bipolar spectrum disorder or schizophrenia, as determined by MINI International Neuropsychiatric Interview (MINI) and/or currently diagnosed with one or more DSM-IV axis 1 disorder(s), per Diagnostic and Statistical Manual of Mental Disorders, 4th Edition.
2. Have a significant acute or chronic coexisting illness (cardiovascular, gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)), immunological, metabolic (including diabetes and cardiovascular disease), neurodevelopmental or any condition which contraindicates, in the Principal Investigator's judgement, entry to the study
3. Currently taking (from Visit 1 onwards) or have previously taken (last 4 weeks prior to Visit 1) psychoactive medication (anxiolytics, sedatives, hypnotics, anti-psychotics, anti-depressants, anti-convulsants, centrally acting corticosteroids, opioid pain relievers)
4. Currently taking (from Visit 1 onwards) medication or dietary supplements that the Principal Investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results (e.g. melatonin, St. John's Wort, Rescue® products including Rescue Remedy®, Rescue® Energy, Rescue® Pastilles, Rescue® Pearls, Rescue Sleep® Rescue PlusTM, omega-3 dietary supplements (including fish oil), Cannabidiol (CBD), non-steroidal anti-inflammatory drugs (NSAIDS), over-the-counter sleep medication (not categorized as sedatives, hypnotics or anti-depressants), anti-coagulants, anti-cholinergic drugs or acetylcholinesterase inhibitors, proton pump inhibitors, anti-histamines that cause drowsiness, pseudoephedrine)
5. Recent (within last 4 weeks prior to Visit 1) or ongoing antibiotic therapy
6. Currently taking (from Visit 1 onwards) concentrated sources of probiotics and/or prebiotics other than the provided study products (e.g., probiotic/prebiotic tablets, capsules, drops or powders), including yoghurt / yoghurt drinks
7. Pregnant or lactating female, or pregnancy planned during the intervention period
8. Have self-reported dyslexia
9. History of or current alcohol, drug, or medication abuse (self-reported)
10. Self-declared illicit drug users (including cannabis and cocaine) in the past 1 month prior to Visit 1
11. Excessive alcohol consumption (consuming \> 8 units of alcohol for men and \> 6 units of alcohol for women in a single session) \> 3 times per week for 3 weeks prior to Visit 1
12. Significant change in tobacco, snuff, nicotine or e-cigarette usage habits in the past 1 month before Visit 1 or planned cessation of the use of these products during the intervention period
13. Contraindication to any substance in the investigational product
14. Participation in another study with any investigational product or drug within 60 days of Visit 1
15. Principal Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study
16. Participant under administrative or legal supervision
17. Previous participation in the ChillEx study

Primary outcomes:
measure: State Trait Anxiety Inventory (STAI)-state total score
timeFrame: from baseline to 8 weeks
Secondary outcomes:
measure: Change in Cortisol awakening response (CAR)
timeFrame: from baseline to 8 weeks
measure: Change in perceived stress (Visual Analog Scale (VAS)-stress)
timeFrame: from baseline to 8 weeks
measure: Change in DASS-21, depression scale score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in DASS-21, anxiety scale score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in DASS-21, stress scale score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in HADS, depression score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in HADS, anxiety score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in PSS, total score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in BL-VAS, alertness score from baseline (Visit 3) to 8 weeks (Visit 5)
timeFrame: from baseline to 8 weeks
measure: Change in BL-VAS, contentment score
timeFrame: from baseline to 8 weeks
measure: Change in BL-VAS, calmness score
timeFrame: from baseline to 8 weeks
measure: Change in Pittsburgh Sleep Quality Index (PSQI), total score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, duration of sleep score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, sleep disturbance score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, sleep latency score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, daytime dysfunction due to sleepiness score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, sleep efficiency score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, subjective sleep quality score
timeFrame: from baseline to 8 weeks
measure: Change in PSQI, use of medication sleep score
timeFrame: from baseline to 8 weeks
measure: Change in evening cortisol
timeFrame: from baseline to 8 weeks
Other outcomes:
measure: IPAQ-short, physical activity level score
timeFrame: from baseline to 4 weeks, 8 weeks and 10 weeks
measure: Detection of Probiotic in feces
timeFrame: from baseline to 8 weeks
measure: STAI-state
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Changes in Cortisol awakening response (CAR)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Changes in evening cortisol
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Changes in Visual Analog Scale (VAS)-stress (VAS-stress)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Depression, anxiety, stress scale (21 items) (DASS-21)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Hospital anxiety and depression scale (HADS)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Cohen's perceived stress scale (PSS)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Bond-Lader visual analogue scale (BL-VAS)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Pittsburgh sleep quality index (PSQI)
timeFrame: from baseline to 4 weeks and 10 weeks
measure: Fecal microbiota composition
timeFrame: from baseline to 8 weeks
measure: Compliance of study product
timeFrame: 10 weeks
Locations:
city: Cork
country: Ireland
facility: Atlantia Food Clinical Trials Ltd
city: Kenilworth
country: United Kingdom
facility: MediNova Warwickshire Dedicated Research Centre
city: Northwood
country: United Kingdom
facility: MediNova North London Dedicated Research Centre
city: Romford
country: United Kingdom
facility: MediNova Research East London Clinical Studies Centre
city: Shipley
country: United Kingdom
facility: MediNova Yorkshire Dedicated Research Centre
city: Sidcup
country: United Kingdom
facility: MediNova South London Dedicated Research Centre, Queen Mary's Hospital
city: Wokingham
country: United Kingdom
facility: MediNova West London Dedicated Research Centre
Study officials:
affiliation: Medinova East London Dedicated Research Center
name: Balgit Chhokar
role: STUDY_DIRECTOR
References: