Clinical Trials for the Treatment of Secondary Wasting and Cachexia Perspectives on Exercise and Wasting 1 Elsworth R. Buskirk Physiological Research Center, The Pennsylvania State University, University Park, Pennsylvania 16802 ABSTRACT Recommendations for endpoints in clinical trials of wasting that involve exercise should involve selection that clearly identifies the effects of exercise. Broad endpoints such as morbidity and mortality must be corrected for the effects of age, smoking, hypertension, etc. in order to gain adjusted information pertinent to exer cise. Selectio n of varia bles related to phys iolo gica l funct ion altho ugh more specific i.e., maxi mal oxyg en uptake, must still be viewed from the perspective that other variables may contribute to the values measured. Nevertheless, physiological information obtained from performance tests may well provide useful endpoints. In this rega rd, V ˙ 0 2 max, heartrat e and pulmo nary ventilat ion at fixed work load s, musc ular stre ngth , reac tion time, flexibility, blood gases, cardiac output, stroke volume, serum lactate, and properties of skeletal muscle such as mito chon dria conc entra tion and comp onen ts relat ed to musc le ener getic s, e.g., aden osin e triph osp hate. In add ition exercise will defi nit ely imp act bod y mass and composition as wel l as configuration. The latter is assessable through utilization of somatogramography. Analysis of muscle depends on muscle biopsy and mag- netic resonance spectroscopy. Neither of these methods has been employed in clinical trials to the best of our knowledge. Thus, one needs evidence that exercise in the clinical trial provides a discrete effect on performance capa bilit ies, body statu s and biolo gica lly import ant variables. J. Nutr. 129: 295S–302S , 1999. KEY WORDS: ● exercise ● wasting ● cardiovascular dise ase semi-starvat ion ● bed rest ● skeletal muscle ● somatogramography ● magnetic resonance It is com mon kno wle dge tha t exe rci se dev elo ps and /or improves functional capacity and delays many disabilities that accompany old age. Chronic diseases are postponed through regular exercise. It is quite likely that physical activity and fitness are directly linked to the maintenance of health and longevity. A variety of trials have shown that regular physical activity leads to improvements in risk factors such as blood lipid profiles, hypertension, poor glucose tolerance, etc. Both morbi dity and mor tal ity have bee n sho wn to be fav ora bly impacted by regular exercise (Blair et al. 1989, Kushi et al. 1997, Lee and Paffenbarger 1996, Paffenbarger et al. 1994, Pa ffe nba rge r and Lee 1996). Thu s, exerci se has pro ven a valua ble beha vioral /env ironmental adjun ct in the diagnosis and treatment of a variety of conditions/diseases. While not universally utilizable, properly prescribed regular exercise can produ ce mean ingf ul positi ve chan ges in body comp ositio n, metabolism, energetics, self sufficiency and general well-being in both healthy and compromised individuals. Specific endpoints in relation to the effect of exercise on the prevention of wasting or recovery from wasting involve decision making in regard not only to morbidity and mortality but to body composition, systems performance and physiolog- ical function. Selection of endp oints involves selection of discrete meaningful variables that provide information solely attributable to exercise. Such selection is no easy task. Atten- tion here will be paid to some previous investigations, their findings and some suggestions particularly in regard to skeletal muscle. In the limited space available I have also chosen to briefly review two conditions that produce wasting ie semi-starvation and bed rest, provide a brief focus on skeletal muscle and wasting, and mention a simple analytical technique for eval- uating body configuration in wasting (somatogramography) as well as a more complicated evaluation of muscle energetics and metabolism with magnetic resonance spectroscopy. RELATIVE RISK/MORTALITY The value of regular exercise has been conclusively dem- onstrated in recent years through the efforts of several epide- miologists who have evaluated results from several large groups who differed in regular physical activity. Three of the many available studies are summarized here with a focus on mortality and relative risk. In general relative risk was inversely propor- 1 Presented at the workshop entitle d: “Clinical Trials for the Treatmen t of Secon dary Wasting and Cache xia: Selection of Appropr iate Endpoints ,” May 22–23, 1997, Bethesda, MD. The workshop was sponsored by the Food and Drug Administration, Office of AIDS Research, National Cancer Institute, National In- stitute of Mental Health, Brist ol-Me yers Squibb, Abbott Laboratories, Serono Laboratories, Inc., American Institute for Cancer Research, Roxane Laboratories, National Institute of Drug Abuse, SmithKline Beecham, National Institute of Aging, Eli Lilly Company and the American Society for Nutritional Sciences. Workshop proceedings are published as a supplement to The Journal of Nutrition . Guest Editors for this supplement publication were D. J. Raiten and J. M. Talbot, Life Sciences Research Office, American Society for Nutritional Sciences, Bethesda, MD. 0022-3166/99 $3.00 © 1999 American Society for Nutritional Sciences. 295S
