Clinical trial NCT01172314: Effects of Essential Amino Acid Intake on Net Protein Synthesis in Weight-losing Non-small Cell Lung Cancer Patients
Official title: Effects of Essential Amino Acid Intake on Net Protein Synthesis in Weight-losing Non-small Cell Lung Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-small Cell Lung Cancer
Keywords: NSCLC
Weight loss
protein metabolism
essential amino acid intake
Lead sponsor: Texas A&M University
Sponsor class: OTHER
Collaborators: name: University of Arkansas
First posted: 2010-07-29
Enrollment: 47
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Weight loss commonly occurs in lung cancer patients, negatively influencing their quality of life, treatment response and survival. Gains in lean body mass are difficult to achieve in cancer unless specific metabolic abnormalities are targeted. It is our hypothesis that a nutritional supplement containing a high amount of essential amino acids will target the metabolic alterations of cancer patients. Preliminary research performed in our laboratory in elderly supports this hypothesis. We hypothesize that intake of an essential amino acid nutritional supplement will positively influence protein synthesis rate in advanced non-small cell lung cancer (NSCLC) patients. Furthermore, insight in the underlying mechanism of the higher anabolic response of the essential amino acid supplement will be examined. This information will potentially enable us to formulate a supplement that is more effective than normal food intake, and that will reduce the need for muscle protein breakdown.

Detailed description: In this study, we will test the following hypothesis: A high-leucine essential amino acid mixture stimulates whole body protein synthesis (and in this way protein anabolism) to a larger extent than a regular balanced mixture of total (essential and non-essential) amino acids in NSCLC patients with and without recent weight loss. The principal endpoint will be the extent of stimulation of protein synthesis rate as this is the principal mechanism by which either amino acid or protein intake causes muscle anabolism. This project will provide important clinical information, based on novel fundamental basic knowledge on the process and the specific underlying mechanisms of muscle wasting in patients with NSCLC, and the role of EAA as a potential anabolic substrate. In this way, it will provide preliminary data for the development of nutritional strategies that will prevent or even stop this process of ongoing muscle loss in NSCLC.

Eligibility criteria: Inclusion Criteria:

1. Recently diagnosed with Stage III (unresectable) or Stage IV lung cancer (only for the NSCLC group)
2. Ability to sign informed consent
3. Age 40 years and older

Exclusion Criteria:

1. Previous anti-cancer therapy (e.g. radiotherapy, chemotherapy) or surgery less than 4 weeks prior to the experiment.
2. Presence of fever within the last 3 days
3. Established diagnosis of Diabetes Mellitus
4. BMI \> 35 kg/m2
5. Untreated metabolic diseases including hepatic or renal disorder
6. Presence of acute illness or metabolically unstable chronic illness
7. Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
8. Diagnosis of moderate to severe chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) ≤ 70% of referen¬ce FEV1 (only for the healthy control group)
9. Use of supplements enriched with amino acids
10. Any other condition according to the PI or study physicians would interfere with proper conduct of the study / safety of the patient
11. Failure to give informed consent

Primary outcomes:
measure: Acute change in Net whole body protein synthesis rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Acute change in Whole body myofibrillar protein breakdown rate
timeFrame: Up to 2 years
measure: Acute change in Whole body collagen breakdown rate
timeFrame: Up to 2 years
measure: Acute change in Urea turnover rate
timeFrame: Up to 2 years
measure: Acute change in Arginine turnover rate
timeFrame: Up to 2 years
measure: Acute change in Liver protein synthesis rate
timeFrame: Up to 2 years
measure: Acute change in plasma Insulin concentrations
timeFrame: Up to 2 years
measure: Acute change in plasma Amino acid concentrations
timeFrame: Up to 2 years
measure: Acute change in plasma Glucose concentrations
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Marielle PK Engelen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease. Am J Clin Nutr. 2016 Jun;103(6):1458-64. doi: 10.3945/ajcn.115.125187. Epub 2016 May 4.
citation: Engelen MPKJ, Safar AM, Bartter T, Koeman F, Deutz NEP. High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer. Ann Oncol. 2015 Sep;26(9):1960-1966. doi: 10.1093/annonc/mdv271. Epub 2015 Jun 25.