title: 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.
  
  
  METHODS
  We organized a prospective 20-week, randomized, double-blind, placebo-controlled pilot trial of hemodialysis patients.
  
  
  METHODS
  This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.affiliation: Geriatric Division, Department of Medicine, Northport Veteran Affairs Medical Center, Northport, New York 11768, USA. shingshing.yeh@va.gov
authors.forename: Shing-Shing
authors.initials: SS
authors.lastname: Yeh
authors.forename: Mozhdeh
authors.initials: M
authors.lastname: Marandi
authors.forename: Henry C
authors.initials: HC
authors.lastname: Thode
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Levine
authors.forename: Thomas
authors.initials: T
authors.lastname: Parker
authors.forename: Troy
authors.initials: T
authors.lastname: Dixon
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D019167:Appetite Stimulants / Q000008:administration & dosage*; D001806:Blood Urea Nitrogen; D001823:Body Composition; D001835:Body Weight; D002100:Cachexia / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D015444:Exercise; D006801:Humans; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D011446:Prospective Studies; D021122:Protein Subunits / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D006435:Renal Dialysis; D055070:Resistance Training; D012709:Serum Albumin / Q000032:analysis; D015430:Weight Gain
chemical_list: D019167:Appetite Stimulants; D016207:Cytokines; D010919:Placebos; D021122:Protein Subunits; D018124:Receptors, Tumor Necrosis Factor; D012709:Serum Albumin; D002784:Cholesterol; D019290:Megestrol Acetate