Research Brief
Report of a Pilot, Double-Blind, Placebo-Controlled Study of Megestrol Acetate in Elderly Dialysis Patients With Cachexia

https://doi.org/10.1053/j.jrn.2009.08.005Get rights and content

Objective

We examined the effects of megestrol acetate versus placebo and progressive resistance physical exercise on weight, lean muscle mass, quality of life, ability to exercise, proinflammatory cytokines, and anti-inflammatory cytokines, and their correlations with one another.

Design

We organized a prospective 20-week, randomized, double-blind, placebo-controlled pilot trial of hemodialysis patients.

Setting

This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center.

Subjects

We studied nine male hemodialysis patients who had two or more of the following: albumin level <4.0 g/dL, total cholesterol <150 mg/dL, protein catabolic rate <0.8 g/kg/day, and predialysis serum urea nitrogen <60 mg/dL. Their ages were 50 to 83 years. Two were diabetic, and seven were nondiabetic.

Interventions

Interventions included megestrol acetate (MA) or placebo 800 mg oral daily for 20 weeks, along with weight resistance physical therapy with weights twice a week before dialysis. Patients were followed prospectively for an additional 4 weeks.

Main Outcome Measurements

Weight, body composition, activities of daily living, ability to exercise, and plasma cytokine levels were measured.

Results

At 24 weeks, the MA group had a statistically significant weight gain (11.1-pound increase vs. 1.5-pound decrease for the placebo group, P = .018), body fat gain (6.2-pound increase vs. a 0.4-pound decrease for the placebo group, P = .044) and fat-free mass gain (5-pound increase vs. a 1.2-pound decrease in the placebo group). The MA group also had a greater tendency toward increased appetite and sense of well-being. The MA group showed a greater improvement in ability to exercise (mean change in rate of perceived exertion (RPE), 4.7) vs. the placebo group (mean change in RPE vs. 0.5, P = .02). Elevated cytokine levels were evident at baseline in both groups. In all patients, increases in weight, fat-free mass, sense of well-being, appetite, and ability to exercise were negatively correlated with tumor necrosis factor receptor subunit p75 (P < .05). There was a trend toward all of these parameters to be negatively correlated with tumor necrosis factor receptor subunit p55, although only sense of well-being was statistically significant (P < .05).

Conclusion

In a pilot trial in dialysis patients, MA showed significant benefits in improving weight and ability to exercise. Cytokine changes were correlated with weight gains and increases in fat-free mass.

Section snippets

Setting

The MA or placebo was administered at the Northport VAMC Outpatient Research Unit to 11 out of 40 consecutively seen outpatient dialysis subjects between 1999 and 2002, who fulfilled the study criteria and signed a consent form. Two subjects failed the initial screening.

Patients aged 40 years and older, diagnosed with cachexia and receiving dialysis, were included in the study. Inclusion criteria required at least two of the following: albumin <4.0 g/dL, total cholesterol <150 mg/dL, protein

Patient Characteristics

Of nine study patients, there were minimal differences in baseline characteristics of those six who completed the trial and the three who withdrew. However, the MA patients tended to be younger. The average age for the MA group was 67.5 years, and 75.4 years for the placebo group. However, this difference in age did not seem to correlate with a difference in baseline functions, comorbid conditions, or laboratory values. Nevertheless, it may have biased the study results. For all patients

Discussion

With such a small study group, it is difficult to draw definitive conclusions. However, we were able to show significant improvements in weight (11.1 pounds; Fig. 1), fat mass (6.2 pounds; Fig. 2), and ability to exercise in cachectic dialysis patients who were given MA compared with the placebo group. This result is consistent with the results of other investigations.18, 19

We also found improved quality of life and appetite and a decrease in CRP with MA treatment, similar to what Rammohan

Acknowledgments

This study was supported by an unrestricted research grant from the Bristol-Myers Squibb Co., the manufacturer of megestrol acetate (Megace) oral solution. We thank Dr. Merrill J. Egorin and Dr. William Evans for study suggestions and guidance. We also thank Dr. Enrique Pastoriza, Dr. Gaylord Hoffert, Dr. Shawn Amann, Dr. Asrat Tesfa, Dr. Sherri Lovitt, and Dr. Jeffery S. Olson for technical assistance and support. Thanks are also extended to the Dialysis Unit, Northport Veteran Affairs Medical

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