BACKGROUND:Older persons often lose muscle mass, strength, and physical function. This report describes the challenges of conducting a complex clinical investigation assessing the effects of anabolic hormones on body composition, physical function, and metabolism during aging. METHODS: HORMA is a multicenter, randomized double masked study of 65-90-year-old community dwelling men with testosterone levels of 150-550 ng/dL and IGF-1 < 167 ng/dL. Subjects were randomized to transdermal testosterone (5 or 10 g/day) and rhGH (0, 3, or 5 microg/kg/day) for 16 weeks. Outcome measures included body composition by DEXA, MRI, and (2)H(2)O dilution; muscle performance (strength, power, and fatigability), VO2peak, measures of physical function, synthesis/breakdown of myofibrillar proteins, other measures of metabolism, and quality of life. RESULTS: Major challenges included delay in startup caused by need for 7 institutional contracts, creating a 142-page manual of operations, orientation and training, creating a 121-page CRF; enrollment inefficiencies; scheduling 16 evaluations/ subject; overnight admissions for invasive procedures and isotope infusions; large data and image management and transfer; quality control at multiples sites; staff turnover; and replacement of a clinical testing site. Impediments were largely solved by implementation of a web-based data entry and eligibility verification; electronic scheduling for multiple study visits; availability of research team members to educate and reassure subjects; more frequent site visits to validate all source documents and reliability of data entry; and intensifying quality control in testing and imaging. The study exceeded the target goal of 108 (n = 112) completely evaluable cases. Two interim DSMB meetings confirmed the lack of excessive adverse events, lack of center effects, comparability of subjects, and that distribution of subjects and enrollment will not jeopardize outcomes or generalizability of results. CONCLUSIONS: Flexibility and rapidly solving evolving problems is critical when conducting highly complex multicenter metabolic studies.
RCT Entities:
BACKGROUND: Older persons often lose muscle mass, strength, and physical function. This report describes the challenges of conducting a complex clinical investigation assessing the effects of anabolic hormones on body composition, physical function, and metabolism during aging. METHODS: HORMA is a multicenter, randomized double masked study of 65-90-year-old community dwelling men with testosterone levels of 150-550 ng/dL and IGF-1 < 167 ng/dL. Subjects were randomized to transdermal testosterone (5 or 10 g/day) and rhGH (0, 3, or 5 microg/kg/day) for 16 weeks. Outcome measures included body composition by DEXA, MRI, and (2)H(2)O dilution; muscle performance (strength, power, and fatigability), VO2peak, measures of physical function, synthesis/breakdown of myofibrillar proteins, other measures of metabolism, and quality of life. RESULTS: Major challenges included delay in startup caused by need for 7 institutional contracts, creating a 142-page manual of operations, orientation and training, creating a 121-page CRF; enrollment inefficiencies; scheduling 16 evaluations/ subject; overnight admissions for invasive procedures and isotope infusions; large data and image management and transfer; quality control at multiples sites; staff turnover; and replacement of a clinical testing site. Impediments were largely solved by implementation of a web-based data entry and eligibility verification; electronic scheduling for multiple study visits; availability of research team members to educate and reassure subjects; more frequent site visits to validate all source documents and reliability of data entry; and intensifying quality control in testing and imaging. The study exceeded the target goal of 108 (n = 112) completely evaluable cases. Two interim DSMB meetings confirmed the lack of excessive adverse events, lack of center effects, comparability of subjects, and that distribution of subjects and enrollment will not jeopardize outcomes or generalizability of results. CONCLUSIONS: Flexibility and rapidly solving evolving problems is critical when conducting highly complex multicenter metabolic studies.
Authors: D Rudman; A G Feller; H S Nagraj; G A Gergans; P Y Lalitha; A F Goldberg; R A Schlenker; L Cohn; I W Rudman; D E Mattson Journal: N Engl J Med Date: 1990-07-05 Impact factor: 91.245
Authors: E Todd Schroeder; Jiaxiu He; Kevin E Yarasheski; Ellen F Binder; Carmen Castaneda-Sceppa; Shalender Bhasin; Christina M Dieli-Conwright; Miwa Kawakubo; Ronenn Roubenoff; Stanley P Azen; Fred R Sattler Journal: Eur J Appl Physiol Date: 2011-07-12 Impact factor: 3.078
Authors: Kevin E Yarasheski; Carmen Castaneda-Sceppa; Jiaxiu He; Miwa Kawakubo; Shalender Bhasin; Ellen F Binder; E Todd Schroeder; Ronenn Roubenoff; Stan P Azen; Fred R Sattler Journal: Am J Clin Nutr Date: 2011-05-04 Impact factor: 7.045
Authors: Shalender Bhasin; E Jiaxiu He; Miwa Kawakubo; E Todd Schroeder; Kevin Yarasheski; Gregory J Opiteck; Alise Reicin; Fabian Chen; Raymond Lam; Jeffrey A Tsou; Carmen Castaneda-Sceppa; Ellen F Binder; Stanley P Azen; Fred R Sattler Journal: J Clin Endocrinol Metab Date: 2009-10-16 Impact factor: 5.958
Authors: Chi-Sung Chiu; Hans Weber; Sharon Adamski; Albert Rauch; Michael A Gentile; Stephen E Alves; Gary Kath; Osvaldo Flores; Hilary A Wilkinson Journal: BMC Musculoskelet Disord Date: 2011-10-28 Impact factor: 2.362