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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01154400
• Other study ID #: 109237
• Status: Completed
• Phase: N/A
• First received: June 24, 2010
• Last updated: October 11, 2012
• Start date: May 2009
• Est. completion date: July 2011

Study information

• Verified date: October 2012
• Source: Texas A&M University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Dietary Supplement:
• Casein protein hydrolysates
15 g casein protein hydrolysates + 15 g maltodextrin
• Whey protein hydrolysates
15 g whey protein isolate + 15 g maltodextrin
• Casein protein hydrolysates + LEU
15 g casein protein hydrolysate + 2.1 g LEU (40% of EAA content) + 15 g maltodextrin
• Whey protein hydrolysates + LEU
15 g whey protein isolate + 1.5 g LEU (40% of EAA content) + 15 g maltodextrion

Locations

Country	Name	City	State
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Texas A&M University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in net whole body protein balance	Net whole body protein synthesis before and after protein feeding	6 hours	No
Secondary	Change in whole body protein synthesis rate	Whole body protein synthesis before and after protein feeding	6 hours	No
Secondary	Change in whole body protein breakdown rate	Whole body protein breakdown rate before and after protein feeding	6 hours	No
Secondary	Change in whole body collagen breakdown	Whole body collagen breakdown before and after protein feeding	6 hours	No
Secondary	Change in insulin concentration	Plasma insulin during protein feeding	6 hours	No
Secondary	Change in glucose concentration	Plasma glucose concentration during protein feeding	6 hours	No
Secondary	Change in plasma amino acid levels	Plasma amino acid level during protein feeding	6 hours	No
Secondary	Change in whole body myofibrillar protein breakdown rate	Whole body myofibrillar protein breakdown before and after protein feeding	6 hours	No