選択的アンドロゲン受容体モジュレーターは健常高齢者の除脂肪体重と身体機能を改善

選択的アンドロゲン受容体モジュレーターは健常高齢者の除脂肪体重と身体機能を改善するというPhase Ⅱのランダム化比較試験を紹介します。

James T. Dalton, et al: The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. Journal of Cachexia, Sarcopenia and Muscle 10.1007/s13539-011-0034-6

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http://www.springerlink.com/content/0111w0166870k603/fulltext.html

蛋白同化ステロイドやテストステロンは筋肉量増強作用はありますが、副作用の問題で容易に使用することはできません。前立腺がん、女性の男性化、心臓血管系の副作用などがあります。

一方、選択的アンドロゲン受容体モジュレーターGTx-024 (enobosarm)は非ステロイド性の経口剤で、動物実験では少ない副作用で筋肉量増強作用を認めています。そこで今回、Phase Ⅱのランダム化比較試験を行いました。

結果ですが、GTx-024 (enobosarm)3mg投与群とプラセボで比較すると、筋肉量、身体機能、インスリン抵抗性は介入群で有意に改善し、副作用（主に頭痛、背部痛）は両群で同等でした。ただし、長期間投与時の副作用は不明です。

以上より、サルコペニアや悪液質による筋肉量低下に対して、GTx-024 (enobosarm)3mg投与が有効な可能性があります。主作用は間違いないと思いますが、やはり副作用が心配です。副作用の心配が少なければ、将来的に臨床で使用されることの多い薬剤になる可能性があります。

Abstract
Background
Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation.

Methods
A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety.

Results
GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P<0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups.

Conclusion
GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.