Study on the Effects of a Probiotic on Autonomic and Psychological Stress

Stress, Psychological Clinical Trial

Official title:

A Double Blind Placebo Controlled Study on the Effects of a Probiotic on Autonomic and Psychological Stress Responses in Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02417454
• Other study ID #: 20000229
• Status: Completed
• Phase: Phase 3
• First received: April 7, 2015
• Last updated: October 17, 2017
• Start date: September 2015
• Est. completion date: August 2017

Study information

• Verified date: October 2017
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effects of a probiotic blend on qualitative (subjective interviews and self-reporting) and quantitative (changes in brain activity, heart rate, cortisol, and reactivity) measures of stress in healthy undergraduate students.

Description:

There is a burgeoning literature involving nonhuman animal and human studies linking the microbiota environment in the gut to brain-behaviour relations. For example, animal studies demonstrate that germ-free rodents show heightened HPA-axis responses to stress compared to gnotobiotic animals. There are also a number of nonhuman and human studies that show positive effects of reducing stress after being treated with different probiotics. For example, in one recent double blind study in humans using standardized questionnaires indicated a greater reduction of stress and anxiety symptoms after one month of supplementation with a probiotic formulation compared to placebo. The groups were also differentiated by urinary cortisol levels after treatment. Other studies have found positive effects of probiotic treatment and stress reduction using other probiotics. Accordingly, there is accumulating empirical evidence from animal and human studies of the positive effects of probiotic treatment on stress reduction.

In this study, the investigators will investigate the stress reduction effects of the Lallemand Health Solutions (LHS) Probio'Stick® on healthy undergraduate students. The study will be conducted at the McMaster LIVELab, which is capable of collecting both physiological and behavioural measures from groups of up to 100 participants at a time.

Registration into this clinical trial will require students be screened via McMaster's SONA system (mcmaster.sona-systems.com). After the screening, participants that are eligible to participate will be given the option to register for an information meeting at which point one may opt to enrol in the study or not.

Once in the study, participants will undergo an initial screening in the LIVELab where they will be exposed to auditory, visual, and performance based stressors to measure a baseline. After such point, they will be randomized to receive Probio'Stick® or placebo for a 6-week, once daily, probiotic treatment at home. Following the 6 week intervention, participants will return to the lab for a second testing using the same procedures to establish a change from baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Answering "Yes" to questions 3, 8 and 9 of the Cohen's Perceived Stress Scale.

• Willingness to complete questionnaires, records, and diaries associated with the study and to complete all site visits.

• Willingness to discontinue consumption of fermented foods or probiotics (e.g. yogurts, with live, active cultures, or supplements).

• Ability to provide informed consent.

Exclusion Criteria:

• Must not be currently taking another probiotic regiment or another investigational product within 3 months of the screening visit.

• Must not currently be taking medications for depression or anxiety, including benzodiazepines, SSRIs, or antipsychotics or receiving counselling for depression or anxiety.

• Must not be immune-compromised or immuno-suppressed (e.g. AIDS, lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participants).

• Must not have experienced bloody diarrhea in the past month prior to beginning the study.

• Must not have undergone any surgery within the three months prior to beginning the study, particularly surgeries involving the colon.

• Must not have any soy or milk allergy.

• Must not be pregnant or breast-feeding or planning on becoming pregnant.

• Must not have used of any antibiotic drug (e.g., neomycin, rifaximin) within 1 month of screening.

Related Conditions & MeSH terms

• Stress, Psychological

Intervention

Dietary Supplement:
• ProbioStick
One sachet daily, without or without meals (3 x 10^9 CFU per sachet) (Lactobacillus helveticus R0052 and Bifidobacterium longum subsp. longum R0175)

Other:
• Placebo
One sachet daily, without or without meals (0 CFU per sachet)

Locations

Country	Name	City	State
Canada	McMaster LIVELab	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Lallemand Health Solutions

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V, Tompkins T. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil. 2014 Apr;26(4):510-20. doi: 10.1111/nmo.12295. Epub 2013 Dec 30. — View Citation

Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, Houdeau E, Fioramonti J, Bueno L, Theodorou V. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012 Nov;37(11):1885-95. doi: 10.1016/j.psyneuen.2012.03.024. Epub 2012 Apr 26. — View Citation

Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. — View Citation

European Food Safety Authority. Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance. EFSA Journal. 2012;10(6).

Garneau P, Labrecque O, Maynard C, Messier S, Masson L, Archambault M, Harel J. Use of a bacterial antimicrobial resistance gene microarray for the identification of resistant Staphylococcus aureus. Zoonoses Public Health. 2010 Nov;57 Suppl 1:94-9. doi: 10.1111/j.1863-2378.2010.01358.x. — View Citation

Gasser F. Safety of lactic acid bacteria and their occurrence in human clinical infections. Bull Inst Past. 1994;92:45-67.

Kullisaar T, Songisepp E, Mikelsaar M, Zilmer K, Vihalemm T, Zilmer M. Antioxidative probiotic fermented goats' milk decreases oxidative stress-mediated atherogenicity in human subjects. Br J Nutr. 2003 Aug;90(2):449-56. — View Citation

Lang PJ, Bradley MM, Cuthbert BN. International affective picture system (IAPS): Affective ratings of pictures and instruction manual.. Technical Report A-8. University of Florida, Gainesville, FL.; 1995.

Lutgendorff F, Akkermans LM, Söderholm JD. The role of microbiota and probiotics in stress-induced gastro-intestinal damage. Curr Mol Med. 2008 Jun;8(4):282-98. Review. — View Citation

Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011 Jul-Aug;2(4):256-61. doi: 10.4161/gmic.2.4.16108. Epub 2011 Jul 1. — View Citation

Palomar MM, Maldonado Galdeano C, Perdigón G. Influence of a probiotic lactobacillus strain on the intestinal ecosystem in a stress model mouse. Brain Behav Immun. 2014 Jan;35:77-85. doi: 10.1016/j.bbi.2013.08.015. Epub 2013 Sep 7. — View Citation

Salminen S, von Wright A, Morelli L, Marteau P, Brassart D, de Vos WM, Fondén R, Saxelin M, Collins K, Mogensen G, Birkeland SE, Mattila-Sandholm T. Demonstration of safety of probiotics -- a review. Int J Food Microbiol. 1998 Oct 20;44(1-2):93-106. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in right frontal electroencephalography (EEG)/brain activity	Is a measure of stress/arousal	Visit 1 and Visit 2 (6 weeks apart)
Primary	Changes in salivary cortisol concentrations	Collected via Salivette®, before and after each session in the lab.	Pre and Post Visit 1 and Visit 2 (6 weeks apart)
Primary	Change in the magnitude of startle response	Measured as facial electromyography (EMG) change	Visit 1 and Visit 2 (6 weeks apart)
Primary	Changes in sympathetic nervous system activation	Calculated as a measure of Heart Rate Variability (HRV) from electrocardiography (ECG) data	Visit 1 and Visit 2 (6 weeks apart)
Secondary	Changes in Anxiety Scores as determined by the Beck Anxiety Inventory (BAI)		Visit 1 and Visit 2 (6 weeks apart)
Secondary	Changes in Stress Scores as determined by Cohen's Perceived Stress Scale (PSS)		Visit 1 and Visit 2 (6 weeks apart)
Secondary	Changes in General Affect Scores as determined by the Positive and Negative Affect Scale (PANAS)		Visit 1 and Visit 2 (6 weeks apart)
Secondary	Changes in Stress Scores as reported on a 1-10 Likert Scale		Visit 1 and Visit 2 (6 weeks apart)

External Links

•   Lallemand Health Solutions
•   McMaster LIVELab
•   McMaster SONA Recruitment