Effects of Essential Amino Acid Intake on Net Protein Synthesis in Weight-losing Non-small Cell Lung Cancer Patients

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.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Dietary supplement: EAA+LEU vs total AA; Dietary supplement: Total AA vs EAA+LEU

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.

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EAA+LEU vs total AA	Dietary supplement: EAA+LEU vs total AA; 15 g as a bolus
Experimental: Total AA vs EAA+LEU	Dietary supplement: Total AA vs EAA+LEU; 15 g as a bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute change in Net whole body protein synthesis rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute change in Whole body myofibrillar protein breakdown rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in Whole body collagen breakdown rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in Urea turnover rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in Arginine turnover rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in Liver protein synthesis rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in plasma Insulin concentrations	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in plasma Amino acid concentrations	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years
Acute change in plasma Glucose concentrations	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years

Collaborators and Investigators

• Sponsor: Texas A&M University
• Collaborators: University of Arkansas
• Investigators: Principal Investigator: Marielle PK Engelen, PhD, University of Arkansas

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: July 27, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (Estimate): July 29, 2010

Study Record Updates

• Last Update Posted (Actual): April 22, 2019
• Last Update Submitted That Met QC Criteria: April 19, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: NSCLC; Weight loss; protein metabolism; essential amino acid intake
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 112254