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Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances (NAKED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02272725
Recruitment Status : Completed
First Posted : October 23, 2014
Results First Posted : May 16, 2017
Last Update Posted : December 12, 2018
Information provided by (Responsible Party):
Grant S Lipman, Stanford University

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.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Exercise-associated Hyponatremia Perceived Exertion Drug: Ibuprofen Drug: Placebo Phase 3

Detailed Description:

This study will be conducted during the fifth stage of a 6-stage ultramarathon foot race that covers a total of 250 kilometers. Data will be collected during four separate events over the course of the coming year. All races are run by the RacingThePlanet™ 4-desert race series with locations including: Jordan, Ecuador, China, and Chile. The evening after stage 4, participants will be reminded to check in at the medical tent prior to stage 5 start, and at that time the participants will be weighed and given their study drug packet (ibuprofen or visually identical placebo). Approximately 80% of the finishers complete the 80-kilometer Stage 5 in less than 19 hours, so the majority of participants will ingest 1600mg of ibuprofen (400mg q 4 hours x 4 doses). The optimal adult dosing for analgesia is 400mg every 4 hours, with a maximum daily dose of 3200mg ((1999). Product information: Motrin™, ibuprofen. Kalamazoo, MI, Pharmacia & Upjohn Company.)

Immediately after crossing the finish line of Stage 5, participants will be reweighed, then seated in the study tent where a fingertip blood sample will be obtained via lancet and capillary collection tube (Mock, Morrison, & Yatscoff, 1995) then analyzed for Na, Cr and BUN (utilizing a Chem-8 cartridge) onsite immediately after collection using an iSTAT® point-of- care analyzer (Abbott; East Windsor, NJ). Any participant who did not complete any stage prior to stage 5 will be removed from the competition and the study. Both the point-of-care device and the digital scale will be calibrated for prior to taking measurements. At this point, the study is over and there is no further participant responsibilities.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
Study Start Date : March 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
tasteless and inert tablets
Drug: Placebo
Tasteless and inert visually identical (to ibuprofen) pills
Other Name: sugar pill

Active Comparator: Ibuprofen
Each tablet containing 400mg of ibuprofen
Drug: Ibuprofen
Other Name: motrin

Primary Outcome Measures :
  1. Acute Kidney Injury [ Time Frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours ]
    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.

Secondary Outcome Measures :
  1. Perceived Exertion [ Time Frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours ]
    A Borg score of perceived exertion will be measured at the finish line immediately following completion of a 50 mile ultramarathon to measure what affect ibuprofen had on perceived exertion as analgesia may have made the endurance event perceived as less exertional. Scores range from 7 - 20, with higher scores indicative of greater amount of exertion.

  2. Exercise-Associated Hyponatremia [ Time Frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours ]
    The count of participants experiencing exercise-associated hyponatremia (defined as < 135 mEq) will be estimated from measured point-of-care blood test at the finish line immediately following completion of a 50 mile ultramarathon. This outcome measure is a biochemical reading, that may not necessarily be a clinical adverse event.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02272725

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United States, California
Stanford University
Stanford, California, United States, 94034
Sponsors and Collaborators
Stanford University
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Principal Investigator: Grant S Lipman, MD Stanford University
Publications of Results:
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Responsible Party: Grant S Lipman, Principal Investigator, Stanford University Identifier: NCT02272725    
Other Study ID Numbers: 31907
First Posted: October 23, 2014    Key Record Dates
Results First Posted: May 16, 2017
Last Update Posted: December 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Grant S Lipman, Stanford University:
acute kidney injury
exercise-associated hyponatremia
Additional relevant MeSH terms:
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Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Water-Electrolyte Imbalance
Metabolic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action