Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances

NCT02272725 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 31907
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated hyponatremia (EAH) during an ultramarathon foot race. There is currently much debate over whether NSAID ingestion during endurance events contributes to acute kidney injury. Endurance events often ignite a "perfect storm" of physiologic insults- heat stress, dehydration, and myopathy- which can all negatively impact kidney function. There is a concern that NSAIDs may further potentiate these negative effects as well as contribute to EAH through its anti-diuretic affect. To date, no powered, prospective study has ever examined the effects of NSAIDs on either of these two biochemical outcomes Ultramarathon endurance events, defined as any race longer than a marathon (26.2 miles), are increasing in popularity, with a 10% increase in annual participants, and more than 69,000 finishers worldwide in 2013. Considerable literature has documented alterations in serum biochemical profiles of these endurance athletes, with consistent evidence of elevated serum creatinine (Cr) levels in healthy race finishers as well as those seeking medical care. While acute renal failure in ultramarathon runners is a rare occurrence, acute kidney injury is common, ranging from 34% in a single-stage ultramarathon to 55-80% in multi-stage ultramarathons. The evidence is equivocal regarding NSAID ingestion and AKI. One study showed that runners who ingested NSAIDs prior to marathons had greater post-race creatinine levels than matched controls as well as higher rates of hospitalization and acute renal failure. However, this contrasts with several other studies that showed a marked lack of difference in creatinine levels or development of acute kidney injury between NSAID users and non-users during ultramarathons. The only randomized trial to date on this subject found no difference in serum creatinine levels between the NSAID and placebo groups at ultramarathon race end, however conclusions were limited by a small unpowered sample size. Exercise associated hyponatremia (EAH), defined as a serum sodium concentration below 135mEq/L, is recognized as a relatively common issue in endurance running events. The incidence of EAH varies depending upon the distance of the race, with reported values of 3-28% for marathons, 23 - 38% for triathlons and 4-51% in single-stage ultramarathons. EAH is likely under-diagnosed as athletes are often asymptomatic. While EAH most often manifests as non-specific symptoms such as nausea, vomiting, dizziness, and fatigue, it can be a potentially fatal disease that can progress to encephalopathy, seizures, pulmonary edema, and death. There have been no large prospective studies examining the relationship between EAH and NSAID ingestion.

Conditions

Acute Kidney Injury; Exercise-associated Hyponatremia; Perceived Exertion

Keywords

ultramarathon; ibuprofen; acute kidney injury; exercise-associated hyponatremia; exertion

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury

  The participants experiencing acute kidney injury (diagnosed by an increase in creatinine of greater or equal to 1.5x that of estimated baseline creatinine from age and weight) will be from measured point-of-care blood test of the finish line immediately following the completion of a 50 mile ultramarathon. This outcome measure is a biochemical reading, that may not necessarily be a clinical adverse event.

  participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours

Secondary Outcomes (2)

• Perceived Exertion

  participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours

• Exercise-Associated Hyponatremia

  participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

tasteless and inert tablets

Drug: Placebo

Ibuprofen

ACTIVE COMPARATOR

Each tablet containing 400mg of ibuprofen

Drug: Ibuprofen

Interventions

Ibuprofen DRUG

Ibuprofen

Also known as: motrin

Ibuprofen

Placebo DRUG

Tasteless and inert visually identical (to ibuprofen) pills

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any participant in a RacingThePlanet sanctioned event who understands the consent form in English.

You may not qualify if:

• Allergic to any form of non-steroidal anti-inflammatory
• Taken a NSAID or steroid in prior 12 hours
• kidney
• Known to be pregnant or suspected to be pregnant

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94034, United States

Location

Related Publications (1)

• Lipman GS, Shea K, Christensen M, Phillips C, Burns P, Higbee R, Koskenoja V, Eifling K, Krabak BJ. Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emerg Med J. 2017 Oct;34(10):637-642. doi: 10.1136/emermed-2016-206353. Epub 2017 Jul 5.

  PMID: 28679502 RESULT

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Ibuprofen; Sugars

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Dr. Grant Lipman
• Organization: Stanford University School of Medicine

gslipman@stanford.edu

415-290-9286

Study Officials

• Grant S Lipman, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 23, 2014
• Study Start: March 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: January 1, 2017
• Last Updated: December 12, 2018
• Results First Posted: May 16, 2017

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)