Individual Dose-escalated Bi-daily Subcutaneously (sc) Ghrelin in Cancer Cachexia: a Phase I/II Study
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Individual Dose-escalated Bi-daily sc Ghrelin in Cancer Cachexia: a Phase I/II Study|
- To assess the dose of ghrelin in tumour patients with ACS causing optimal stimulation of nutritional intake - minimal dose for maximal nutritional intake (MD-MANI) - or the maximally tolerable dose (MTD), which one occurs first [ Time Frame: bi-weekly ]
- To assess the effect of ghrelin on muscle strength. [ Time Frame: weekly ]
- To assess the toxicity and tolerability, pharmacokinetics and symptoms of eating of ghrelin. [ Time Frame: bi-weekly ]
- To assess the effect of ghrelin on muscle mass, physical function, safety, toxicity and tolerability, pharmacokinetics, symptoms of eating, gastrointestinal motility, inflammation [ Time Frame: weekly ]
|Study Start Date:||June 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
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
As starting dose the investigators choose a dose level which was shown in our last study to be safe in human beings, i.e. 8μg/kg intravenously. With an assumed bioavailability of 25% of subcutaneously administered ghrelin the corresponding dose for dose level 1 is therefore 32 μg/kg. In the first 4 dose levels for each subsequent dose level the dose is increased by 50% compared to the previous one, from the 5th dose level onwards the increase is 25%: Dose level 1 = 32 μg/kg Dose level 2 = 48 μg/kg Dose level 3 = 72 μg/kg Dose level 4 = 108 μg/kg Dose level 5 = 135 μg/kg Dose level 6 = 169 μg/kg Dose level 7 = 211 μg/kg The investigators define the maximum tolerable dose as 20mg ghrelin (equivalent to 5ml) for reasons of the high drug volume to be administered subcutaneously.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00933361
|Cantonal Hospital St. Gallen KSSG|
|St. Gallen, Switzerland, 9000|
|Principal Investigator:||Florian Strasser, PD Dr. MD||Cantonal Spital St. Gallen|