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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University
ClinicalTrials.gov Identifier:
NCT01154400
First received: June 24, 2010
Last updated: October 11, 2012
Last verified: October 2012
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Grant Title: Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in COPD

Resource links provided by NLM:


Further study details as provided by Texas A&M University:

Primary Outcome Measures:
  • Change in net whole body protein balance [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Net whole body protein synthesis before and after protein feeding


Secondary Outcome Measures:
  • Change in whole body protein synthesis rate [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Whole body protein synthesis before and after protein feeding

  • Change in whole body protein breakdown rate [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Whole body protein breakdown rate before and after protein feeding

  • Change in whole body collagen breakdown [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Whole body collagen breakdown before and after protein feeding

  • Change in insulin concentration [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Plasma insulin during protein feeding

  • Change in glucose concentration [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Plasma glucose concentration during protein feeding

  • Change in plasma amino acid levels [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Plasma amino acid level during protein feeding

  • Change in whole body myofibrillar protein breakdown rate [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Whole body myofibrillar protein breakdown before and after protein feeding


Enrollment: 12
Study Start Date: May 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154400

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

No publications provided

Responsible Party: Marielle PKJ Engelen, PhD, PhD, Texas A&M University
ClinicalTrials.gov Identifier: NCT01154400     History of Changes
Other Study ID Numbers: 109237
Study First Received: June 24, 2010
Last Updated: October 11, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Texas A&M University:
casein protein
whey protein
hydrolysates
leucine
protein metabolism
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Caseins
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014