Clinical trial participant John “Duke” Barrientos doesn't know if he's getting the tested drug or a placebo, but he has his suspicions.
“I'm thinking I'm taking the medicine,” said Barrientos, a 74-year-old Omahan. “When the sun gets on me, it's like my arms are on fire.”
Increased sensitivity to sunlight is one of the potential side effects of doxycycline, a common antibiotic often used to treat acne. In this case, researchers at the University of Nebraska Medical Center and 14 other U.S. medical centers are testing whether doxycycline could slow the growth of abdominal aortic aneurysms, sparing patients the $20,000-plus surgery to repair the aorta and preventing deaths.
Barrientos is one of 264 people nationwide who will be part of a $12.2 million study for which UNMC is serving as the clinical coordinating center.
The funding was provided by the National Institutes of Health. The trial grant is large — six times the size of the average NIH research center grant last year.
In addition, said Dr. Jennifer Larsen, UNMC's vice chancellor for research, while UNMC has taken the lead in other clinical trials, this one “is the first that I am aware of where an investigator has taken a concept from the laboratory, his laboratory, and developed the idea for a new treatment based on that science into a large multicenter, NIH-funded clinical trial.”
An estimated 15,000 deaths are attributable to ruptured abdominal aortic aneurysms each year in the U.S. The aorta is a large artery that carries blood from the heart through the chest and abdomen. If an aortic aneurysm bursts, it will prove fatal more than half of the time.
In the absence of medication, patients don't have options for addressing the problem aside from surgery. It can take years before an aneurysm gets big enough (about 5.5 centimeters, or about 2 inches) that the risk of rupture outweighs the risk of surgery.
People often can't believe there's nothing to be done immediately about their aneurysm, said Dr. Jason MacTaggart, an assistant surgery professor at UNMC and a site investigator for the trial. “Most people are, like, 'What? Aren't you going to fix this thing?' ”
A few aneurysms rupture before they reach the 5.5-centimeter mark, said Dr. Timothy Baxter, a UNMC surgery professor and one of the study's four principal investigators. Baxter compares it to living with a ticking time bomb.
Baxter's research on mice has shown that doxycycline inhibits the enzymes that weaken aortic walls, thus causing aneurysms.
“We've known since the late '90s that this drug had this possibility that it could work” to slow the growth of aneurysms, Baxter said. “But it's been difficult to get everything lined up for such a big clinical trial like this.”
Larsen said Baxter “was very much a one-man cheerleading squad for this concept and this trial.”
Barrientos' abdominal aortic aneurysm is 4.7 centimeters, a little larger than it was three years ago when it was first diagnosed. When you see it on a computer screen, the bulge in his artery looks like a cherry tomato.
Risk factors for developing the aneurysms include hardening of the arteries, family history, high blood pressure, high cholesterol and a history of smoking. Barrientos knows of no one in his family with the condition, but he said he started smoking at age 12 and finally quit the habit about 2½ years ago.
People usually can't tell if they have an aneurysm, Baxter said, so most of the ones that doctors find are spotted because a person is getting a CT scan for some other reason, such as a kidney stone or to detect the spread of prostate cancer.
Those who are enrolled in the trial will be followed for two years. Every six months, Baxter said, they will have their blood drawn and get CT scans. The blood from all the sites will be sent to Washington University in St. Louis to be analyzed, and all the scans will be sent to the University of Wisconsin to be reviewed. An investigator from the University of Maryland oversees the trial's management and design.
If some aneurysms are shown to grow quickly, Baxter said, researchers will be able to identify which markers in the blood indicate that is likely to happen. At the end of the study, he said, “we hope to be able to select patients who need closer surveillance or might be the best candidates for drug therapy because they're going to progress more rapidly than others.”
Barrientos, a 20-year Navy man who just retired in April from his security job, said he hopes his aneurysm stops growing. If it gets to 5 centimeters, he said, his doctor wants to put a stent in. He'll find out if it's grown in October, when he gets another CT scan.
Barrientos said he really isn't worried. If it turns out he was taking the placebo rather than the drug, his participation in the study “might help other people with the same problem.”
MacTaggart said people with aneurysms who want to be included in the trial, which is called the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial, should call 402-559-7300.