DURHAM, N.C. -- After leading one of the first large-scale clinical trials to demonstrate the benefits of aerobic exercise on weight loss and cholesterol levels, Duke University Medical Center researchers are now enrolling participants into a trial to study the effects of weight training on reducing cardiovascular risk factors.

Since the body responds differently to resistance training than it does to aerobic exercise, the researchers want to characterize the specific benefits of resistance training, as well as to determine whether adding such exercises to an aerobic program yields synergistic benefits. Just as importantly, the researchers hope their new clinical trial can discern subtle age and gender differences in participants' responses to exercise.

The first five-year trial, dubbed STRRIDE (Studies of Targeted Risk Reduction Interventions through Defined Exercise), demonstrated that only 30 minutes of daily walking prevents weight gain in most sedentary people and that any additional exercise can lead to the loss of weight and fat. Furthermore, the trial demonstrated that aerobic exercise can influence the size of cholesterol-carrying particles, a factor which they argue is more predictive of cardiovascular risk than the standard HDL and LDL screens.

"STRRIDE II is a natural extension of our previous studies and the results should have a major impact on the design of training programs to reduce patients' risks for cardiovascular disease," said Duke cardiologist William E. Kraus, M.D., principal investigator for the new trial.

"The results of both STRRIDE trials should provide us with a new understanding of the mechanisms that underlie the benefits we see from exercise," Kraus continued. "Exercise guidelines issued recently by the Centers for Disease Control and Prevention and the National Academy of Science are based more on expert opinion and consensus than on data gained from controlled clinical studies, since there are precious few of the latter. With these trials, we hope to be able to provide that scientific data."

The National Heart, Lung, and Blood Institute, part of the National Institutes of Health, is supporting the five-year STRRIDE II trial with a $3.1 million grant, after having invested $4.3 million in the first trial. Joining Duke in the trial will be investigators from East Carolina University, led by exercise physiologist Joseph Houmard, Ph.D.

For the trial, the researchers will enroll sedentary and overweight participants between the ages of 18 and 70 at the Duke Center for Living and ECU's Human Performance Laboratory. Participants will then be randomized into one of three groups: resistance training alone, aerobic training alone, and a combination of both. A much smaller subgroup will be randomized into high-intensity aerobic exercise.

As in the first trial, participants will not be allowed to change their normal diet during the course of the study, so that any changes measured can be attributed to the exercise. Throughout the course of the study, researchers will take blood samples to determine the subtle and specific changes in cholesterol particle size and number, as well as changes in the levels of glucose and other lipids.

The resistance training group will follow a regimen of eight to 10 exercises that equally work the upper and lower body, while the aerobic exercise group will exercise on cycle ergometers, treadmills or elliptical trainers. All participants will go through a four-month inactive control period, followed by six months of increasing exercise.

"Americans clearly do not exercise enough, and even the experts cannot come to a consensus on what is the optimal type or amount of exercise," said Houmard, who directs ECU's human performance laboratory. "Some say exercise an hour a week, some say just do something, anything. We hope that this series of trials will help refine the message by providing clear data upon which to base sound recommendations."

The underlying hypothesis guiding the STRRIDE trials is that exercise changes skeletal muscle, which plays a key role in the metabolism of glucose and lipids, such as cholesterol. Exercise also influences the type and location of body fat, which is also a key risk for cardiovascular disease, said the scientists.

The researchers are beginning to understand the benefits of aerobic exercise. For example, in a report based on STRRIDE findings published in the New England Journal of Medicine in 2002, they said aerobic exercise caused individual cholesterol particles to become larger and fluffier. This was a key finding since it is known that as the size of cholesterol particles decreases, the cardiovascular risks increase.

The researchers hope that by the end of the current five-year trial, they will have gained clearer insights into the effects of resistance training as well.

"We know that as a result of resistance training, muscle cells get bigger, but they do not change their characteristics," Kraus said. "On the other hand, aerobic exercise alters the characteristics of the cells without changing their size. Our hypothesis is that both types of exercise could yield benefits greater than the sum of the parts."

Other Duke members of the team include Cris Slentz, Ph.D., Connie Bales, Ph.D., Brian Annex, M.D., and Gregory Samsa, Ph.D.