Ghrelin Administration for Chronic Respiratory Failure: A Randomized Dose-Comparison Trial

Matsumoto, Nobuhiro; Miki, Keisuke; Tsubouchi, Hironobu; Sakamoto, Akihiro; Arimura, Yasuji; Yanagi, Shigehisa; Iiboshi, Hirotoshi; Yoshida, Makoto; Souma, Ryosuke; Ishimoto, Hiroshi; Yamamoto, Yoshihiko; Yatera, Kazuhiro; Yoshikawa, Masayuki; Sagara, Hironori; Iwanaga, Tomoaki; Mukae, Hiroshi; Maekura, Ryoji; Kimura, Hiroshi; Nakazato, Masamitsu; Kangawa, Kenji

doi:10.1007/s00408-015-9685-y

Cited by 11 publications

(13 citation statements)

References 23 publications

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“…In contrast with our previous study and the present main multicenter dose‐finding study , 3‐week high‐dose ghrelin‐PR treatment did not significantly improve the primary outcome of mean change in peak

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o 2 compared with low‐dose ghrelin in the present population; there are two possible explanations. (i) The mean change from pretreatment to 3 weeks of high‐dose ghrelin‐PR treatment in the present study had a larger SD compared with that of the previous study , which means that (a) there were both “responders” and “nonresponders” to high‐dose ghrelin with PR, so that investigating which patients are likely to benefit from ghrelin treatment with PR is likely to become an issue to be addressed in the future; and (b) the small number of enrolled patients might have affected the results.…”

Section: Discussioncontrasting

confidence: 99%

“…After each patient was registered, synthetic human ghrelin 120 μg or 60 μg was dissolved in 2 mL of 3.75% mannitol solution in a vial. All vials prepared were stored frozen at −30°C from the time of dispensing until the time of preparation for injection as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…More recently, a multicenter, randomized, dose‐finding trial, in which the effects of the effects of two doses, i.e. 2 μg/kg and 1 μg/kg, of ghrelin combined with pulmonary rehabilitation (PR) for 3 weeks were investigated in 44 patients with CRF, showed that the improvement in peak oxygen uptake (

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) was greater when receiving 2 μg/kg than 1 μg/kg of ghrelin .…”

Section: Introductionmentioning

confidence: 99%

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Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Miki

Maekura

Nakazato

et al. 2015

Clinical Respiratory J

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Section: Discussioncontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

\overset{normalV}{true} o_{2}

) was greater when receiving 2 μg/kg than 1 μg/kg of ghrelin .…”

Section: Introductionmentioning

confidence: 99%

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Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Miki

Maekura

Nakazato

et al. 2015

Clinical Respiratory J

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“…Kodama and colleagues showed ghrelin to suppress airway inflammation and increase functional exertion capacity in patients with chronic respiratory failure [73]. Miki and colleagues later showed that ghrelin enhanced exercise capacity, expiratory pressure and improved respiratory symptoms in COPD patients [83,243] and showed benefits on exertional dyspnea [244], These effects may be dose-dependent [245,246]. For lung cancer, treatment with the potent ghrelin analog anamorelin has shown benefits on appetite, lean mass retention, performance and quality of life [133,134,135].…”

Section: Pulmonary Diseasementioning

confidence: 99%

Therapeutic Potential of Targeting the Ghrelin Pathway

Colldén

Tschöp

Müller

2017

IJMS

124

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Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems’ metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

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“…There are wide difference among studies in the definition of cachexia, although some of them have taken weight loss into account as part of the definition. [27][28][29][30][31][32][33] Four interventional studies using ghrelin and octanoic acid-rich formula have been reported in the field of COPD, including two studies with weight loss >7.5% over 6 months 32,33 and 2 studies with BMI <21 kg/m 234, 35 as the definition of cachexia. On the other hand, there is no published interventional research targeting cachexia in cancer, heart failure, and CKD.…”

Section: Recent Cachexia Research In Japanmentioning

confidence: 99%

Cachexia research in Japan: facts and numbers on prevalence, incidence and clinical impact

Konishi¹,

Ishida²,

Springer³

et al. 2016

J cachexia sarcopenia muscle

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Even though most clinical data on cachexia have been reported from Western countries, cachexia may be a growing problem in Asia as well, as the population in this area of the world is considerably larger. Considering the current definitions of obesity and sarcopenia in Japan, which are different from the ones in Western countries, the lack of a distinct cachexia definition in Japan is strinking. Only one epidemiological study has reported the prevalence of cachexia using weight loss as part of the definition in patients with stage III or IV non‐small cell lung cancer. Although the reported prevalence of 45.6% is within the range of that in Western countries (28–57% in advanced cancer), we cannot compare the prevalence of cachexia in other types of cancer, heart failure, chronic obstructive pulmonary disease (COPD), and kidney disease (CKD) between Japan and Western countries. In patients with heart failure, one third of Japanese patients has a body mass index <20.3 kg/m2 whereas the prevalence of underweight is 13.6% in reports from Western countries. These results may suggest that there are more cachectic heart failure patients in Japan, or that using the same definition like Western countries leads to gross overestimation of the prevalence of cachexia in Japan. The rate of underweight patients in COPD has been reported as 31–41% in COPD and seems to be high in comparison to the prevalence of cachexia in Western countries (27–35%). The reported lowest quartile value of BMI (19.6 kg/m2) in CKD may match with the prevalence of cachexia in Western countries (30–60%). The number of clinical trials targeting cachexia is very limited in Japan so far.

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Ghrelin Administration for Chronic Respiratory Failure: A Randomized Dose-Comparison Trial

Cited by 11 publications

References 23 publications

Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Therapeutic Potential of Targeting the Ghrelin Pathway

Cachexia research in Japan: facts and numbers on prevalence, incidence and clinical impact

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