Hydrolyzed Casein and Whey Protein Supplementation and the Addition of Leucine to Induce Protein Anabolism in Malnourished COPD Patients

Grant Title: Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in COPD

The aim of this study is the first aim of a NIH project that consists of 3 aims. The first aim examines the acute effects of two high-quality milk proteins (casein vs. whey) on whole-body and muscle protein metabolism in COPD patients with severe loss of muscle mass and the effects of adding leucine. The principal endpoints will be the extent of stimulation of net whole body protein synthesis as this is the principal mechanism by which either amino acid or protein intake causes muscle anabolism. After determining the optimal nutritional formulation based on the first aim we will continue to work on the second and third aim where fish oil supplementation will be part of the nutritional intervention as well.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Dietary supplement: Casein protein hydrolysates; Dietary supplement: Whey protein hydrolysates; Dietary supplement: Casein protein hydrolysates + LEU; Dietary supplement: Whey protein hydrolysates + LEU

Detailed Description

Cachectic COPD patients are characterized by a decreased muscle protein synthesis and an elevated myofibrillar protein breakdown. A substantial number of these patients, characterized by an enhanced systemic inflammatory response, fails to respond to nutritional therapy, which is of clinical relevance as weight gain to nutritional therapy is a significant, independent predictor of mortality in COPD.

In the present study, the acute protein anabolic effect of two high-quality milk protein supplements in COPD will be examined by comparing a hydrolyzed casein and whey protein meal. We make use of hydrolyzed proteins to correct for absorption differences. Furthermore the effects of these milk proteins with or without enrichment of leucine will be investigated.

Variables of interest are: net whole body protein synthesis; whole body protein synthesis and breakdown rate; whole body myofibrillar protein breakdown rate; whole body collagen breakdown; kinetics of insulin; glucose; amino acid levels.

It is the investigators hypothesis that a nutritional supplement containing casein protein and high levels of leucine will target the metabolic alterations of these cachectic COPD patients and will specifically stimulate protein anabolism. The knowledge gained from this study will benefit our insight in terms of promotion of protein anabolism in COPD patients. The long-term goal is to reformulate nutritional composition in accord with the effects of COPD on protein metabolism in order to ameliorate or even prevent progressive muscle wasting in these subjects, and improve their quality of life and survival rates.

• Study Type: Interventional
• Enrollment (Actual): 12
• 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: 45 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of moderate to severe chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) ≤ 70% of reference FEV1
• Shortness of breath on exertion
• Age 45 years and older
• Clinically stable condition and not suffering from respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever) at least 4 weeks prior to the study
• Cachexia based on the criteria: Body mass index ≤ 25 kg/m2 and/or FFM-Index: FFM/height2 ≤ 17 (males), 15 (females) kg/m2 and/or recent involuntary weight loss

Exclusion Criteria:

• Established diagnosis of malignancy
• Presence of fever within the last 3 days
• Established diagnosis of Diabetes Mellitus
• Untreated metabolic diseases including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Recent myocardial infarction (less than 1 year)
• Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
• Allergy to cow's milk protein
• Any other condition according to the PI or study physicians would interfere with proper conduct of the study / safety of the patient
• Failure to give informed consent

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Casein protein hydrolysates; 15 g casein protein hydrolysates and 15 g maltodextrin	Dietary supplement: Casein protein hydrolysates; 15 g casein protein hydrolysates + 15 g maltodextrin; Other Names: Casein
EXPERIMENTAL: Whey protein hydrolysates; 15 g whey protein hydrolysates and 15 g maltodextrin	Dietary supplement: Whey protein hydrolysates; 15 g whey protein isolate + 15 g maltodextrin; Other Names: Whey
EXPERIMENTAL: Casein protein hydrolysates + LEU; 15 g casein protein hydrolysates + 2.1 g LEU (40% of EAA content) + 15 g maltodextrin	Dietary supplement: Casein protein hydrolysates + LEU; 15 g casein protein hydrolysate + 2.1 g LEU (40% of EAA content) + 15 g maltodextrin; Other Names: Casein + LEU
EXPERIMENTAL: Whey protein hydrolysates + LEU; 15 g whey protein hydrolysates + 1.5 g LEU (40% of EAA content) + 15 g maltodextrin	Dietary supplement: Whey protein hydrolysates + LEU; 15 g whey protein isolate + 1.5 g LEU (40% of EAA content) + 15 g maltodextrion; Other Names: Whey + LEU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in net whole body protein balance	Net whole body protein synthesis before and after protein feeding	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in whole body protein synthesis rate	Whole body protein synthesis before and after protein feeding	6 hours
Change in whole body protein breakdown rate	Whole body protein breakdown rate before and after protein feeding	6 hours
Change in whole body collagen breakdown	Whole body collagen breakdown before and after protein feeding	6 hours
Change in insulin concentration	Plasma insulin during protein feeding	6 hours
Change in glucose concentration	Plasma glucose concentration during protein feeding	6 hours
Change in plasma amino acid levels	Plasma amino acid level during protein feeding	6 hours
Change in whole body myofibrillar protein breakdown rate	Whole body myofibrillar protein breakdown before and after protein feeding	6 hours

Collaborators and Investigators

• Sponsor: Texas A&M University

Publications and helpful links

General Publications

• Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion. Clin Nutr. 2014 Apr;33(2):211-20. doi: 10.1016/j.clnu.2013.06.014. Epub 2013 Jul 1.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: June 24, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (ESTIMATE): June 30, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: COPD; whey protein; protein metabolism; leucine; casein protein; hydrolysates
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: 109237