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

• ClinicalTrials.gov Identifier: NCT01154400
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Last Update Posted: October 15, 2012
• Sponsor: Texas A&M University
• Information provided by (Responsible Party): Marielle PKJ Engelen, PhD, Texas A&M University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Dietary Supplement: Casein protein hydrolysates; Dietary Supplement: Whey protein hydrolysates; Dietary Supplement: Casein protein hydrolysates + LEU; Dietary Supplement: Whey protein hydrolysates + LEU	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: Grant Title: Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in COPD
• Study Start Date: May 2009
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Whey + LEU

Outcome Measures

Primary Outcome Measures :

1. Change in net whole body protein balance [ Time Frame: 6 hours ]
   Net whole body protein synthesis before and after protein feeding

Secondary Outcome Measures :

1. Change in whole body protein synthesis rate [ Time Frame: 6 hours ]
   Whole body protein synthesis before and after protein feeding
2. Change in whole body protein breakdown rate [ Time Frame: 6 hours ]
   Whole body protein breakdown rate before and after protein feeding
3. Change in whole body collagen breakdown [ Time Frame: 6 hours ]
   Whole body collagen breakdown before and after protein feeding
4. Change in insulin concentration [ Time Frame: 6 hours ]
   Plasma insulin during protein feeding
5. Change in glucose concentration [ Time Frame: 6 hours ]
   Plasma glucose concentration during protein feeding
6. Change in plasma amino acid levels [ Time Frame: 6 hours ]
   Plasma amino acid level during protein feeding
7. Change in whole body myofibrillar protein breakdown rate [ Time Frame: 6 hours ]
   Whole body myofibrillar protein breakdown before and after protein feeding

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

Texas A&M University

Investigators

• Principal Investigator: Marielle Engelen, PhD; Texas A&M University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Marielle PKJ Engelen, PhD, PhD, Texas A&M University
• ClinicalTrials.gov Identifier: NCT01154400
• Other Study ID Numbers: 109237
• First Posted: June 30, 2010
• Last Update Posted: October 15, 2012
• Last Verified: October 2012

Keywords provided by Marielle PKJ Engelen, PhD, Texas A&M University:

casein protein; whey protein; hydrolysates; leucine; protein metabolism; COPD

Additional relevant MeSH terms:

Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Lung Diseases; Respiratory Tract Diseases; Caseins; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action