Individual Dose-escalated Bi-daily Subcutaneously (sc) Ghrelin in Cancer Cachexia: a Phase I/II Study
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Cachexia, a condition of severe malnutrition, negative nitrogen balance, muscle wasting,
weight loss, and anorexia, is a frequent affecting more than 80% of patients in advanced
cancer disease causing a high burden on patients and their families. Nutritional,
pharmacological, and behavioural interventions for cancer-related ACS and associated symptoms
have, despite the importance for cancer care, limited effect on only a minority of patients.
New strategies are required.
Ghrelin, a 28 amino acid peptide discovered in 1999, is predominantly secreted by gastric
endocrine cells and is an endogenous ligand for the growth hormone secretagogue (GHS)
receptor. When administered peripherally it stimulates growth hormone secretion, food intake,
triggers a positive energy balance, produces weight gain through a central mechanism
involving hypothalamic neuropeptides and has anti-inflammatory effects. A recently completed
trial on intravenous ghrelin in advanced cancer patients with ACS reports good tolerability
and safety of single intravenous application of 2 and 8μg/kg Ghrelin.
Given the facts that ACS is a major burden in patients suffering advanced cancer disease and
ghrelin is a major signal for stimulating food intake, promoting positive energy balance and
weight gain and may have anti-inflammatory effect it remains to be determined whether the
administration of ghrelin will have a positive clinical effect on cancer anorexia/ cachexia
syndrome ACS. The next logical clinical development step is a proper dose-finding study of
twice daily subcutaneous administration and proof-of-concept of main outcomes.