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

NCT01734473 | Completed

• 1 other identifier: 2012-0561
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

COPD

Keywords

COPD; Protein synthesis; Protein breakdown; Muscle wasting; Leucine; Hydrolyzed; Casein protein; Carbohydrates

Outcome Measures

Primary Outcomes (2)

• Net whole-body protein synthesis

  Change in net whole-body protein synthesis (whole-body protein synthesis - whole-body protein breakdown)

  0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post-protein meal

• Net whole-body protein synthesis with different levels of protein intake (Fifth Study Day)

  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)

  before each sip feeding in the second hour of a level of protein intake ( at 120, 140 and 160 min)

Secondary Outcomes (15)

• Whole-body protein synthesis

  0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post-protein meal

• Whole-body protein breakdown

  0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post-protein meal

• Splanchnic extraction

  0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min post-protein meal

• Body composition

  1 day

• Skeletal and respiratory muscle strength

  1 day

Other Outcomes (1)

• Occurrence of (serious) adverse events

  Up to 1 year

Study Arms (5)

Study day 1

EXPERIMENTAL

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

Study day 2

EXPERIMENTAL

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

Study day 3

EXPERIMENTAL

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

Study day 4

EXPERIMENTAL

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

Study Day 5

EXPERIMENTAL

4 levels of hydrolyzed casein protein + carbohydrates

Dietary Supplement: 4 levels of hydrolyzed casein protein + carbohydrates

Interventions

Hydrolyzed casein protein DIETARY_SUPPLEMENT

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

Also known as: PeptoPro

Study day 1

Hydrolyzed casein protein + carbohydrates DIETARY_SUPPLEMENT

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

Also known as: PeptoPro + maltodextrin

Study day 2

Hydrolyzed casein protein + leucine DIETARY_SUPPLEMENT

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

Also known as: PeptoPro + leucine

Study day 3

Hydrolyzed casein protein + carbohydrates + leucine DIETARY_SUPPLEMENT

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

Also known as: PeptoPro + maltodextrin + leucine

Study day 4

4 levels of hydrolyzed casein protein + carbohydrates 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.

Also known as: 4 levels of PeptoPro + maltodextrin

Study Day 5

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Texas A&M University: lead

Study Sites (1)

Texas A&M University

College Station, Texas, 77843, United States

Location

Related Publications (2)

• 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.

  PMID: 30150004 DERIVED

• 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.

  PMID: 30100106 DERIVED

Related Links

• PeptoPro

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Muscular Atrophy

Interventions

Carbohydrates; maltodextrin; Leucine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Marielle PK Engelen, PhD

  Texas A&M University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: November 27, 2012
• Study Start: November 28, 2012
• Primary Completion: May 27, 2015
• Study Completion: May 27, 2015
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)