Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
Condition: Acute Kidney Injury; Exercise-associated Hyponatremia; Perceived Exertion
MeSH terms: Acute Kidney Injury; Hyponatremia
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Ibuprofen; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ibuprofen; Tasteless and inert visually identical (to ibuprofen) pills
Other intervention name(s): motrin; sugar pill
Intervention MeSH terms: Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: ultramarathon; ibuprofen; acute kidney injury; exercise-associated hyponatremia; exertion