Casein Protein and Leucine Supplementation in Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Texas A&M University
Sponsor:
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University
ClinicalTrials.gov Identifier:
NCT01734473
First received: November 21, 2012
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

Weight loss commonly occurs in patients with COPD, negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of this weight loss and independently increases mortality. This study will provide relevant clinical information in regards to the anabolic properties of specific dietary substrates and their co-active anabolic effects. Hypotheses: 1) That supplementation of a hydrolyzed casein-based protein meal with the addition of carbohydrates is more anabolic than a hydrolyzed casein-based protein meal without carbohydrates in COPD patients and healthy older adults; 2) That leucine addition to a hydrolyzed casein-based protein meal only enhances the protein anabolic response in COPD patients and healthy older adults when carbohydrates are not added to the protein meal; 3) That COPD patients have a more efficient protein anabolic response to a hydrolyzed casein-based protein meal than healthy older adults.

A fifth study day was added to measure protein requirements of included individuals to be able to interpret their response to the other interventions on the other study days, and to test the hypothesis that subjects with lower protein requirements respond less to intervention with leucine and/or carbohydrates. For the 5th additional test day we will first approach the 10 COPD and 10 healthy subjects who already completed the first 4 study days (and signed the re-contact form) to come back for this extra test day. We will (pre-)screen these subjects by phone for eligibility and check for changes in their recent medical history (with help of the (pre-)screening questionnaires in CRF). If all inclusion criteria are still met, these subjects will be asked to provide a written re-consent. If necessary, we will recruit new subjects who will complete only one of the four test days (i.e. the test day on which the hydrolyzed casein-based protein meal with carbohydrates is provided) and the additional 5th study day.


Condition Intervention
COPD
Dietary Supplement: Hydrolyzed casein protein
Dietary Supplement: Hydrolyzed casein protein + carbohydrates
Dietary Supplement: Hydrolyzed casein protein + leucine
Dietary Supplement: Hydrolyzed casein protein + carbohydrates + leucine
Dietary Supplement: 4 different levels of hydrolyzed casein protein: 0, 0.02, 0.05, 0.15 g/kg fat free mass/hr + carbohydrates (fixed ratio protein : carbohydrate)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Casein Protein and Leucine Supplementation to Induce Anabolism in COPD Patients and Healthy Elderly

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Net whole-body protein synthesis [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Change in net whole-body protein synthesis (whole-body protein synthesis - whole-body protein breakdown)

  • Net whole-body protein synthesis with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Change in net whole-body protein synthesis (whole-body protein synthesis - whole-body protein breakdown) with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)


Secondary Outcome Measures:
  • Whole-body protein synthesis [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Change in whole-body protein synthesis

  • Whole-body protein breakdown [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Change in whole-body protein breakdown

  • Percentage of splanchnic extraction [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    The amount of amino acids in the protein meal extracted by the splanchnic tissues after intake

  • Body composition [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Difference in muscle mass, fat mass and bone density between COPD patients and healthy older adults

  • Skeletal and respiratory muscle strength [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Difference in handgrip strength and fatigue and maximum inspiratory and expiratory pressure between COPD patients and healthy older adults

  • Inflammatory mediators [ Time Frame: 90 min before protein meal ] [ Designated as safety issue: No ]
    C-reactive protein, interleukines

  • Hormones [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of insulin

  • Glucose [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Peak plasma concentration (Cmax) of glucose

  • Amino acid concentrations [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post‐protein meal ] [ Designated as safety issue: No ]
    Peak plasma concentration (Cmax) of amino acids

  • Whole-body protein synthesis with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Change in whole-body protein synthesis with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)

  • Whole-body protein breakdown with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Change in whole-body protein breakdown with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)

  • Percentage of splanchnic extraction with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    The amount of amino acids in the protein meal extracted by the splanchnic tissues after intake of 4 different levels of protein (duration of each level: 2 hours) as sip feeding (every 20 minutes)

  • Hormones with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of insulin with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)

  • Glucose with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Peak plasma concentration (Cmax) of glucose with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)

  • Amino acid concentrations with different levels of protein intake (Fifth Study Day) [ Time Frame: before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min) ] [ Designated as safety issue: No ]
    Peak plasma concentration (Cmax) of amino acids with 4 different levels of protein intake (duration of each level: 2 hours) as sip feeding (every 20 minutes)


Other Outcome Measures:
  • Occurrence of (serious) adverse events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Number of (serious) adverse events


Estimated Enrollment: 40
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study day 1
Hydrolyzed casein protein. On each study day participants receive one out of 4 protein meals (interventions). The 4 interventions are given in a randomized order.
Dietary Supplement: Hydrolyzed casein protein
Amount provided is based on the fat-free mass of subject
Other Name: PeptoPro
Experimental: Study day 2
Hydrolyzed casein protein + carbohydrates. On each study day participants receive one out of 4 protein meals (interventions). The 4 interventions are given in a randomized order.
Dietary Supplement: Hydrolyzed casein protein + carbohydrates
Amount provided is based on the fat-free mass of subject
Other Name: PeptoPro + maltodextrin
Experimental: Study day 3
Hydrolyzed casein protein + leucine. On each study day participants receive one out of 4 protein meals (interventions). The 4 interventions are given in a randomized order.
Dietary Supplement: Hydrolyzed casein protein + leucine
Amount provided is based on the fat-free mass of subject. Leucine (40% of essential amino acid content)
Other Name: PeptoPro + leucine
Experimental: Study day 4
Hydrolyzed casein protein + carbohydrates + leucine. On each study day participants receive one out of 4 protein meals (interventions). The 4 interventions are given in a randomized order.
Dietary Supplement: Hydrolyzed casein protein + carbohydrates + leucine
Amount provided is based on the fat-free mass of subject. Leucine (40% of essential amino acid content)
Other Name: PeptoPro + maltodextrin + leucine
Experimental: Study Day 5
4 different levels of hydrolyzed casein protein: 0, 0.02, 0.05, 0.15 g/kg fat free mass/hr + carbohydrates (fixed ratio protein : carbohydrate)
Dietary Supplement: 4 different levels of hydrolyzed casein protein: 0, 0.02, 0.05, 0.15 g/kg fat free mass/hr + carbohydrates (fixed ratio protein : carbohydrate)
Other Name: 4 different levels of PeptoPro + maltodextrin

Detailed Description:

The study involves 5 study days. The duration of the first 4 days is approximately 6.5 hours per study day. The duration of the fifth study day is approximately 8 hours. On the first four study days the effects of one protein meal will be examined. On the fifth study day the effect of 4 different levels of protein intake by sip feeding (every 20 minutes) is examined.

Also, subjects will receive a mixture of amino acids (little parts of protein) which are a little bit heavier than normal, called stable isotopes. This is the so-called stable isotope method to investigate protein behavior in the body (protein kinetics). Altogether about 75 ml of blood will be drawn per study day to assess outcome measures.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria COPD subjects:

  • Ability to walk, sit down and stand up independently
  • Age 45 years or older
  • Ability to lie in supine or elevated position for 5.5 hours
  • Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: Forced Expiratory Volume(FEV1)/Forced Vital Capacity (FVC) < 0.70 and FEV1 < 70% of reference FEV1
  • Clinically stable condition and not suffering from a 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, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the first test day
  • Shortness of breath on exertion
  • Willingness and ability to comply with the protocol, including:

    • Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Inclusion criteria healthy control subjects:

  • Healthy male or female according to the investigator's or appointed staff's judgment
  • Ability to walk, sit down and stand up independently
  • Age 45 years or older
  • Ability to lay in supine or elevated position for 5.5 hours
  • No diagnosis of chronic airflow limitation and compliant to the following criteria: FEV1/FVC > 0.70 and FEV1 ≥ 80% of reference FEV1
  • Willingness and ability to comply with the protocol, including:

    • Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Exclusion Criteria all subjects:

  • Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
  • Established diagnosis of malignancy
  • Established diagnosis of Insulin Dependent Diabetes Mellitus
  • History of untreated metabolic diseases including hepatic or renal disorder
  • Presence of acute illness or metabolically unstable chronic illness
  • Recent myocardial infarction (less than 1 year)
  • Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient
  • BMI of < 18.5 or ≥ 35 kg/m2
  • Dietary or lifestyle characteristics:

    • Use of protein or amino acid containing nutritional supplements within 5 days of first test day
    • Current alcohol or drug abuse
  • Indications related to interaction with study products:

    • Known allergy to milk or milk products
  • Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
  • Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
  • (Possible) pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734473

Contacts
Contact: Marielle PK Engelen, PhD +19792202282 mpkj.engelen@ctral.org
Contact: Renate Jonker +19792195437 r.jonker@ctral.org

Locations
United States, Texas
Texas A&M University Recruiting
College Station, Texas, United States, 77843
Sponsors and Collaborators
Texas A&M University
Investigators
Principal Investigator: Marielle PK Engelen, PhD Texas A&M University
  More Information

Additional Information:
No publications provided

Responsible Party: Marielle PKJ Engelen, PhD, PhD, Texas A&M University
ClinicalTrials.gov Identifier: NCT01734473     History of Changes
Other Study ID Numbers: 2012-0561
Study First Received: November 21, 2012
Last Updated: April 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Texas A&M University:
COPD
Protein synthesis
Protein breakdown
Muscle wasting
Leucine
Hydrolyzed
Casein protein
Carbohydrates

Additional relevant MeSH terms:
Lung Diseases
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 July 24, 2014