Efficacy and safety of Lacticaseibacillus paracasei Lpc-37® in students facing examination stress: A randomized, triple-blind, placebo-controlled clinical trial (the ChillEx study).

2023-10
Brain, behavior, & immunity - health 32

PubMed: 37662485
DOI: 10.1016/j.bbih.2023.100673

Study Design

Type: Randomized Controlled Trial (RCT)
Population: One hundred ninety university students (18-40 y) in a model of chronic examination stress
Methods: Randomized to take 1.56 × 10^10 colony-forming units of Lpc-37 or placebo (1:1) each day for 10 weeks, in a triple-blind, parallel, multicenter clinical trial

Lacticaseibacillus paracasei Lpc-37 (Lpc-37) has previously shown to reduce perceived stress in healthy adults. The ChillEx study investigated whether Lpc-37 reduces stress in a model of chronic examination stress in healthy students. One hundred ninety university students (18-40 y) were randomized to take 1.56 × 10¹⁰ colony-forming units of Lpc-37 or placebo (1:1) each day for 10 weeks, in a triple-blind, parallel, multicenter clinical trial consisting of six visits: two screening visits, a baseline visit, and visits at 4, 8, and 10 weeks after baseline. The primary objective was to demonstrate that Lpc-37 reduces stress, as measured by the change in state anxiety from baseline to just before the first examination, after 8 weeks using the State Trait Anxiety Inventory (STAI-state). Secondary objectives aimed to demonstrate that Lpc-37 modulates psychological stress-induced symptoms and biomarkers related to mood and sleep. An exploratory analysis of fecal microbiota composition was also conducted. There was no difference between Lpc-37 and placebo groups in the change of STAI-state score (estimate 1.03; 95% confidence interval 3.67; p = 0.446). None of the secondary outcomes resulted in significant results when corrected for multiplicity, but exploratory results were notable. Results showed an improvement in sleep-disturbance scores (odds ratio 0.30; 95% CI: 0.11, 0.82; p = 0.020) and reduction in duration of sleep (odds ratio 3.52; 95% CI: 1.46, 8.54; p = 0.005) on the Pittsburgh Sleep Quality Index questionnaire after 8 weeks in the Lpc-37 group compared to placebo. A reduction in Bond Lader VAS-alertness was also demonstrated in the Lpc-37 group compared to placebo (estimate -3.97; 95% CI: -7.78, -0.15; p = 0.042) just prior to the examination. Analysis of fecal microbiota found no differences between study groups for alpha and beta diversity or microbiota abundance. Adverse events were similar between groups. Vital signs, safety-related laboratory measures, and gastrointestinal parameters were stable during the trial. In conclusion, probiotic Lpc-37 was safe but had no effect on stress, mood, or anxiety in healthy university students in this model of chronic academic stress. ClinicalTrials.gov: NCT04125810.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lacticaseibacillus paracasei Lpc-37	—	No Reduction in Stress or Anxiety	Neutral	Small	View source There was no difference between Lpc-37 and placebo groups in the change of STAI-state score (estimate 1.03; 95% confidence interval [CI]: -1.62, 3.67; p = 0.446).
Lacticaseibacillus paracasei Lpc-37	—	Reduced Alertness	Harmful	Small	View source A reduction in Bond Lader VAS-alertness was also demonstrated in the Lpc-37 group compared to placebo (estimate -3.97; 95% CI: -7.78, -0.15; p = 0.042) just prior to the examination.
Lacticaseibacillus paracasei Lpc-37	—	Reduced Circadian Sleep Disturbance	Beneficial	Small	View source Results showed an improvement in sleep-disturbance scores (odds ratio 0.30; 95% CI: 0.11, 0.82; p = 0.020) ... on the Pittsburgh Sleep Quality Index questionnaire after 8 weeks in the Lpc-37 group compared to placebo.
Lacticaseibacillus paracasei Lpc-37	—	Reduced Sleep Duration	Beneficial	Small	View source Results showed ... reduction in duration of sleep (odds ratio 3.52; 95% CI: 1.46, 8.54; p = 0.005) on the Pittsburgh Sleep Quality Index questionnaire after 8 weeks in the Lpc-37 group compared to placebo.