New study looks at carnitine’s role in staving off potentially deadly condition
By Jack Mazurak
A clinical trial of an experimental therapy that could start accepting patients next year in the University of Mississippi Medical Center’s emergency department may help save critically ill sepsis patients.
The trial, funded by a $3.8 million federal grant awarded this spring to Dr. Alan Jones, professor of emergency medicine, will spread to eight other hospitals across the U.S.
Sepsis is a body-wide bacterial infection. Left unchecked, it can cause damage and failure in vital organs, poor oxygenation and life-threateningly low blood pressure. Various studies claim sepsis kills anywhere from 14 to 50 percent of patients diagnosed with it.
Pneumonia, urinary tract or intra-abdominal infections usually cause sepsis. The elderly and people with weakened immune systems are most prone.
As such a deadly condition, physicians and researchers want to find better methods, drugs and therapies to treat sepsis and improve odds of survival.
In Jones’ clinical trial, septic patients will receive intravenous injections of carnitine, a nutrient the body makes naturally.
Carnitine helps cells produce energy. Prior research had suggested septic patients become carnitine deficient, which makes each cell’s energy production drop and the body overall become less efficient.
“While large skeletal muscles might tolerate that situation temporarily, it can wreak havoc on how well major organs function,” Jones said.
Energy output and function of the kidneys, heart, liver and lungs are especially critical during sepsis, while the body tries to fight off a bloodstream infection.
“In sepsis, you become malnourished. The tiny junctions in the kidneys become leaky and you lose carnitine,” he said.
If Jones’ hypothesis of replacing carnitine proves correct, organ function in patients will improve and help their bodies fight off sepsis.
The trial will include 250 people randomized into a control group or one of several different dose-level groups. Researchers will essentially flood participants’ bodies intravenously with carnitine.
“We’ll replace the body’s carnitine with enough so there’s a reserve of it. Then we’ll monitor them throughout their hospital stay and for up to one year,” Jones said. “We’ll look at the change in organ function and probability of this intervention’s success in a phase 3 trial.”
Patients in the control group will receive the normal therapy for sepsis. The test groups will receive normal therapy in addition to carnitine.
“We do have to be very sensitive to the fact that these are critically ill patients. Really, they’re the sickest of the sick,” Jones said. “The great thing about carnitine is that it’s a semi-essential nutrient with really no side effects. So the risk-to-benefit ratio is very favorable.”
Though carnitine is not a drug, rather a nutrient, the clinical trial for the synthetically made supplement being used in the study is regulated by the Food and Drug Administration. The trial also will require approval from UMMC’s Institutional Review Board, which maintains an oversight role in research studies involving human test subjects.
After starting at UMMC, the trial will extend to Carolinas Medical Center in Charlotte N.C., Northwestern University in Chicago, the University of Michigan in Ann Arbor, two sites at Indiana University in Indianapolis, two sites at Beth Israel Deaconess Medical Center in Boston, and Cooper University Hospital in Camden, N.J.
Jones wants all the sites ready to enroll within a year. The sites then will enroll and treat septic patients as they come into ERs throughout the next three and a half years. During the grant’s final six months, Jones and UMMC biostatisticians will analyze the data.
In March, the researchers completed a phase 1 safety study. The National Institute of General Medical Sciences awarded Jones the five-year grant for nearly $3.8 million to pay for this second phase.
A phase 3 trial would test the therapy for effectiveness and safety on an even larger group.