Does Probiotic Supplementation Prevent Kidney Injury During Strenuous Physical Exercise?

Study Overview
=================
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.

Official Title
-----------------
Does Probiotic Supplementation Prevent Kidney Injury During Strenuous Physical Exercise?

Conditions
-----------------
Heat Stress, Kidney Injury

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic, Lactobacillus
* Dietary Supplement: Placebo


Participation Criteria
=================
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>10^10 colony-forming units of a Lactobacillus strain, packaged in a capsule, once daily | Dietary Supplement: Probiotic, Lactobacillus<br>* 10^10 colony-forming units of a Lactobacillus strain, packaged in a capsule, once daily<br>|
| Placebo Comparator: Placebo<br>Inactive substance packaged to be identical to active treatment | Dietary Supplement: Placebo<br>* Inactive substance packaged to be identical to active treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Tubular injury markers measured in urine (e.g. KIM-1, MCP-1, IGFBP-7) combined using structural equations modelling and then combined over the 24 hour post-run period by calculating the area under the curve of this composite outcome variable in the 24 hours after the run. Exact list of markers to be determined based on budget available after sample collection is completed. | 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heat stress, Probiotic, Kidney Injury, Gut permeability