COPD悪液質に対するグレリン：RCT

COPDの悪液質に対するグレリンの効果をみたランダム化比較試験を紹介します。

Miki K, Maekura R, Nagaya N, Nakazato M, Kimura H, et al. (2012) Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. PLoS ONE 7(5): e35708. doi:10.1371/journal.pone.0035708

下記HPで全文見ることができます。
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035708

リサーチクエスチョンは以下の通りです。

P：悪液質のCOPD患者に
I：3週間1日2回グレリン投与＋呼吸リハを行うと
C：プラセボ投与＋呼吸リハを行う場合と比較して
O：6分間歩行距離とQOL：St. George Respiratory Questionnaire (SGRQ)の得点が改善する
D：ランダム化比較試験

悪液質に関しては、Evansなどの診断基準は用いていません。BMI21以下で一秒率FEV1/FVCが70%以下で%FEV1が50%以下などが取り込み基準です。呼吸リハは3週間で週5回、合計15回実施しています。

結果ですが、6分間歩行距離は介入群内では前後で有意差を認めましたが、対照群との比較では有意差を認めませんでした。SGRQ得点は7週間の時点で有意差を認めました。呼吸筋も7週間の時点で有意に改善しました。体重と食事摂取量は有意差なしです。

6分間歩行距離は介入群内、対照群内とも3週間後に有意に改善していますので、これは呼吸リハの効果と言うべきでしょう。QOLは3週間後では両群とも改善していますので、これも呼吸リハの効果でしょうか。7週間後で有意差が出たのはグレリンの効果かもしれません。

サンプルサイズが小さいので、ふこれでグレリンの効果が少ないとは言いきれません。しかし、この研究結果を見る限りでは、グレリンより呼吸リハの効果のほうが大きいという印象を私は持ちます。グレリン＋栄養療法なら有意差が出た可能性もある気がします。

Abstract
Background
Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.

Methodology/Principal Findings
In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.

Conclusions/Significance
In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.