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

The study involves 5 study days. The duration of the first 4 study days is approximately 6.5 hours per day and the duration of the 5th study day is approximately 8 hours. On each of the first 4 study days the effect a casein protein meal with or without leucine and carbohydrates will be examined. On the fifth study day the effect of 4 different levels of casein protein and carbohydrate 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.

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