New Approach for Easing Angina

New Approach for Easing Angina

December 2003
Volume III, Number 6

Researchers at Indiana University School of Medicine and the Indiana Center for Vascular Biology and Medicine (ICVBM) are busy, enrolling patients in the landmark Angiogenic Gene Therapy in Patients with Stable Angina (AGENT 3) trial. By combining a modified version of a cold virus with a gene therapy product designed to promote the growth of new vessels, scientists hope to develop an effective new treatment for patients living with stable angina, a condition affecting over six million Americans.

One of the first patients in the Indianapolis arm of the national trial, John Schleicher entered the double-blinded, randomized trial one month ago. Even though Schleicher does not know if he received gene therapy or a placebo, he is quick to point out how differently he feels.

"I feel much better," Schleicher told NHW. "I was taking four or five nitroglycerin tablets a day, and now I hardly take any. I feel very well."

Jeffrey Breall, M.D., principal investigator and director of interventional cardiology and the Clarian Health Catheterization Laboratory, and Dr. Keith March, director of ICVBM, urge more patients to enter the trial. They highlight the fact that enrollment criteria are considerably less strict than requirements for previous gene therapy trials, where the patients faced no other options.

"You don't have to be end stage and hopeless to get into this trial," says Dr. Breall. "This trial is for patients who have had angioplasty, bypass surgery, or a combination of both and are on a reasonable medical regimen, but continue to have a moderate amount of angina. There are millions of these patients out there."

Schleicher's progress is in line with findings from previous Agent trials.

"From the earlier Agent trials, we know that patients are able to do more activities with fewer symptoms, as well as walk farther on a treadmill," notes Dr. Breall. "We are hopeful that we will see these results repeated. We would then be able to proceed to the next phase of the trial to hone down the exact amount of this substance and for whom it would be beneficial."

In the ongoing study, researchers are using a delivery method where the genetic material is infused into the arteries that supply the heart with oxygen.

"We go through the femoral artery, up to the aorta and into the coronary artery, as we would for a regular angiogram or angioplasty," explains Dr. Breall. "We advance a special infusion catheter into the coronary circulation, then slowly deliver the material over the course of several minutes. The method of delivery is relatively nonselective."

The experimental treatment might someday be routinely offered.

"Ultimately, this could be an outpatient procedure because it would be no riskier and not much longer than a diagnostic cardiac catheterization, which is already outpatient," Dr. Breall believes. "In the study, we are keeping patients overnight for monitoring, blood collecting, and protocol purposes. However, from a safety standpoint, this procedure can be done virtually in an hour's time, and people could go home in around 90 minutes."

Early data indicate the therapy may benefit individuals affected by heart conditions once considered hopeless.

"I went into this study somewhat of a skeptic, even though I knew the results of the previous Agent trials," Dr. Breall admits. "But there is nothing like treating a very symptomatic patient and seeing the clinical results for yourself. With two out of two patients experiencing dramatic improvements, I am becoming a believer.

"Trials like this will help push back the frontiers and make drugs like this clinically available in years to come. As recently as five years ago, I used to say that there was little hope for many patients. I can't say that anymore. With these investigational therapies, there is no such thing as a 'no-hope' patient."

The Indiana team hopes to enroll an additional 25 patients by the end of 2004. People ages 30 to 75 with a history of angina due to coronary artery disease may be eligible. For additional information on the AGENT 3 clinical trial, call Julie Lacy, R.N., B.S.N., research nurse coordinator, at 317-962-0138.