Report of a pilot, double-blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia.

Abstract

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.

• Authors: Shing-Shing Yeh, Mozhdeh Marandi, Henry C Thode Jr, Daniel M Levine, Thomas Parker, Troy Dixon, Michael W Schuster
• Journal: Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation (J Ren Nutr) Vol. 20 Issue 1 Pg. 52-62 (Jan 2010) ISSN: 1532-8503 [Electronic] United States
• PMID: 19819724 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Appetite Stimulants
• Cytokines
• Placebos
• Protein Subunits
• Receptors, Tumor Necrosis Factor
• Serum Albumin
• Cholesterol
• Megestrol Acetate

Topics

• Activities of Daily Living
• Aged
• Aged, 80 and over
• Appetite Stimulants (administration & dosage)
• Blood Urea Nitrogen
• Body Composition
• Body Weight
• Cachexia (diagnosis, drug therapy, therapy)
• Cholesterol (blood)
• Cytokines (blood)
• Double-Blind Method
• Exercise
• Humans
• Male
• Megestrol Acetate (administration & dosage)
• Middle Aged
• Pilot Projects
• Placebos
• Prospective Studies
• Protein Subunits (blood)
• Receptors, Tumor Necrosis Factor (blood)
• Renal Dialysis
• Resistance Training
• Serum Albumin (analysis)
• Weight Gain