Clinical trial NCT04985292: Does Probiotic Supplementation Prevent Kidney Injury During Strenuous Physical Exercise?
Official title: Does Probiotic Supplementation Prevent Kidney Injury During Strenuous Physical Exercise?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heat Stress
Kidney Injury
Keywords: Heat stress
Probiotic
Kidney Injury
Gut permeability
Lead sponsor: Göteborg University
Sponsor class: OTHER
First posted: 2021-08-02
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Before each run (each study participant may only be included in one run) approximately half runners are randomized to receive a probiotic supplement and the other half to receive placebo
Primary purpose: PREVENTION

Brief summary: Severe heat strain arising from intense physical work under climate conditions that does not allow sufficient heat dissipation may lead to heat stroke. This severe conditions is hypothesized to be secondary to increased gut permeability and leakage of bacterial toxins across the gut membrane, stimulating a systematic inflammatory response and associated organ injury. Repeated such sub-clinical increases in gut permeability has been suggested to contribute to the high burden of chronic kidney disease among heat-stressed workers. Many marathon runners experience a transient increase in kidney injury biomarkers while running. Probiotics have been studied as a way to decrease gut permeability and reduce systemic inflammation in many settings, including in athletes . However, no study has measured renal outcomes among workers or athletes performing strenuous activity. This is of interest as it could test the hypothesis that gut-induced inflammation is a driver of kidney injury during heat stress, and could point to a possible intervention to add on to efforts to relieve heat strain.

In the present study, recreational or professional runners will be randomized to take a probiotic supplement or placebo during a 4 week period preceding a strenuous physical exercise (minimum 21 km run). Urine samples will be taken before and after the run, and analyzed for markers of renal injury and inflammation.

Detailed description: Participants registered to run in organised half-marathons, marathons and ultramarathons in Southern Sweden will be recruited. They will be asked to abstain from probiotic supplementation (including functional foods with probiotics) for 2 weeks, and then commence a 4-week period of probiotic or placebo supplementation.

At the end of the 4 week treatment period, the participants run the race. Urine samples are taken before and after the race and analysed for kidney injury markers.

Stool samples are taken by participants at the initiation of the treatment period, last stool before the race, and first stool after the race.

Eligibility criteria: Inclusion Criteria:

* Planning to run one of the long-distance races included.

Exclusion Criteria:

* Not having run at least 21 km previously,
* smoking,
* living too far away from the study area,
* unwilling to abstain from probiotic supplementation during treatment period,
* unwilling to abstain from NSAIDs or gut-permeability lowering supplements before the run,
* regular use of prescribed drugs (including hormonal contraceptives).

Primary outcomes:
measure: Urine tubular kidney injury marker (Kidney Injury Molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), Insulin Growth Factor Binding Protein 7 (IGFBP-7)) composite variable aggregated using structural equations modelling.
timeFrame: From before the run to after the run (estimated run times 2-24 hours), morning urine after run, and 24 hours after the run finish. These time point are combined to one main outcome by calculating the area under the curve.
Secondary outcomes:
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Occupational and Environmental Medicine
Study officials:
affiliation: Göteborg University
name: Kristina Jakobsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mansour SG, Verma G, Pata RW, Martin TG, Perazella MA, Parikh CR. Kidney Injury and Repair Biomarkers in Marathon Runners. Am J Kidney Dis. 2017 Aug;70(2):252-261. doi: 10.1053/j.ajkd.2017.01.045. Epub 2017 Mar 28.
citation: Hansson E, Glaser J, Jakobsson K, Weiss I, Wesseling C, Lucas RAI, Wei JLK, Ekstrom U, Wijkstrom J, Bodin T, Johnson RJ, Wegman DH. Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers. Nutrients. 2020 Jun 2;12(6):1639. doi: 10.3390/nu12061639.
citation: Leon LR, Bouchama A. Heat stroke. Compr Physiol. 2015 Apr;5(2):611-47. doi: 10.1002/cphy.c140017.
citation: Vaisberg M, Paixao V, Almeida EB, Santos JMB, Foster R, Rossi M, Pithon-Curi TC, Gorjao R, Momesso CM, Andrade MS, Araujo JR, Garcia MC, Cohen M, Perez EC, Santos-Dias A, Vieira RP, Bachi ALL. Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners. Nutrients. 2019 Jul 22;11(7):1678. doi: 10.3390/nu11071678.