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

NCT ID: NCT01734473

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-28
• Study Completion Date: 2015-05-27

Brief Summary

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.

Detailed Description

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.

Conditions

COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Hydrolyzed casein protein

Intervention Type: DIETARY_SUPPLEMENT

Amount provided is based on the fat-free mass of subject

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.

Group Type: EXPERIMENTAL

Hydrolyzed casein protein + carbohydrates

Intervention Type: DIETARY_SUPPLEMENT

Amount provided is based on the fat-free mass of subject

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.

Group Type: EXPERIMENTAL

Hydrolyzed casein protein + leucine

Intervention Type: DIETARY_SUPPLEMENT

Amount provided is based on the fat-free mass of subject. Leucine (40% of essential amino acid content)

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.

Group Type: EXPERIMENTAL

Hydrolyzed casein protein + carbohydrates + leucine

Intervention Type: DIETARY_SUPPLEMENT

Amount provided is based on the fat-free mass of subject. Leucine (40% of essential amino acid content)

Study Day 5

4 levels of hydrolyzed casein protein + carbohydrates

Group Type: EXPERIMENTAL

4 levels of hydrolyzed casein protein + carbohydrates

Intervention Type: DIETARY_SUPPLEMENT

Amount provided is based on the fat-free mass of subject. The 4 levels are: 0, 0.02, 0.05, 0.15 g casein protein/kg fat free mass/hr. The ratio between protein and carbohydrates is fixed.

Interventions

Hydrolyzed casein protein

Amount provided is based on the fat-free mass of subject

Intervention Type: DIETARY_SUPPLEMENT

Hydrolyzed casein protein + carbohydrates

Amount provided is based on the fat-free mass of subject

Intervention Type: DIETARY_SUPPLEMENT

Hydrolyzed casein protein + leucine

Amount provided is based on the fat-free mass of subject. Leucine (40% of essential amino acid content)

Intervention Type: 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)

Intervention Type: DIETARY_SUPPLEMENT

4 levels of hydrolyzed casein protein + carbohydrates

Amount provided is based on the fat-free mass of subject. The 4 levels are: 0, 0.02, 0.05, 0.15 g casein protein/kg fat free mass/hr. The ratio between protein and carbohydrates is fixed.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

PeptoPro; PeptoPro + maltodextrin; PeptoPro + leucine; PeptoPro + maltodextrin + leucine; 4 levels of PeptoPro + maltodextrin

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Texas A&M University

OTHER

Sponsor Role: lead

Responsible Party

Marielle PKJ Engelen, PhD

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marielle PK Engelen, PhD

Role: PRINCIPAL_INVESTIGATOR

Texas A&M University

Locations

Texas A&M University

College Station, Texas, United States

Countries

United States

References

Jonker R, Deutz NEP, Schols AMWJ, Veley EA, Harrykissoon R, Zachria AJ, Engelen MPKJ. Whole body protein anabolism in COPD patients and healthy older adults is not enhanced by adding either carbohydrates or leucine to a serving of protein. Clin Nutr. 2019 Aug;38(4):1684-1691. doi: 10.1016/j.clnu.2018.08.006. Epub 2018 Aug 16.

Reference Type: DERIVED

PMID: 30150004 (View on PubMed)

Jonker R, Deutz NEP, Ligthart-Melis GC, Zachria AJ, Veley EA, Harrykissoon R, Engelen MPKJ. Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients. Clin Nutr. 2019 Aug;38(4):1833-1843. doi: 10.1016/j.clnu.2018.07.018. Epub 2018 Jul 31.

Reference Type: DERIVED

PMID: 30100106 (View on PubMed)

Related Links

https://www.dsm.com/markets/foodandbeverages/en_US/products/nutraceuticals/peptopro.html

PeptoPro

Other Identifiers

2012-0561

Identifier Type: -

Identifier Source: org_study_id