Clinical trial NCT01787682: Nutritional and Functional Changes in Heart Failure and COPD
Official title: Metabolic and Functional Changes in Relation to Nutritional Status in Chronic Heart Failure and Chronic Obstructive Pulmonary Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Heart Failure
Chronic Obstructive Pulmonary Disorder
Keywords: CHF
Protein digestion
Fat digestion
Gut function
Glucose absorption
Muscle function
Lead sponsor: Texas A&M University
Sponsor class: OTHER
First posted: 2013-02-11
Enrollment: 99
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Weight loss commonly occurs in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disorder (COPD), negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of weight loss in CHF and COPD patients but patients also have reductions in fat mass and bone density, independent of the severity of the disease state. The purpose of this cross-sectional study is to provide detailed insight in disease related gut function by obtaining information on gut permeability, digestion and absorption of glucose, fat and protein in CHF and COPD patients compared to matched healthy controls. This will provide required information that is necessary to implement new strategies to develop optimal nutritional regimen in CHF and COPD. The hypothesis is that CHF and COPD are related to decreased gut function and absorption, leading to decreased anabolic response. Second, this decreased nutritional status is linked to reduced muscle functioning and possibly decreased cognition. In addition, we will examine the effect of aging on by comparing gut function digestion and absorption of the CHF and COPD aged matched healthy controls to a group of young healthy subjects.

Detailed description: This study involves one test day of approximately 7-8 hours. On this test day subjects will ingest a sugar drink to assess gut permeability and gut function, and a protein meal to measure digestion/absorption and the anabolic response to food intake. Subjects will also receive a mixture of amino acids that are made a little heavier than normal, called stable isotopes. This stable isotopes is used to investigate protein behavior in the body (protein kinetics). Blood (100-120 ml in total) and urine samples will be collected over 7 hours.

Eligibility criteria: Inclusion criteria CHF subjects:

* Ability to walk, sit down and stand up independently
* Age 45 years or older
* Ability to lie in supine or elevated position for 7 hours
* Diagnosis of Chronic Heart Failure; under regular care by cardiologist
* NYHA class II-IV
* Reduced ejection fraction (\<45%) assessed in the past 2 years
* Clinically stable condition; no hospitalization 4 weeks preceding first study day
* Willingness and ability to comply with the protocol

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 8 hours
* Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: 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

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 (older control group)
* Age between 20-30 years old (young group)
* Ability to lay in supine or elevated position for 7 hours
* No diagnosis of CHF
* Willingness and ability to comply with the protocol

Exclusion Criteria:

* Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only)
* History of untreated metabolic diseases including hepatic or renal disorder
* Presence of acute illness or metabolically unstable chronic illness
* Presence of fever within the last 3 days
* Body mass index \>40 kg/m2 (healthy subjects only)
* 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
* Use of protein or amino acid containing nutritional supplements within 5 days of first study day
* Current use of long-term oral corticosteroids (CHF only)
* Use of short course of oral corticosteroids within 4 weeks preceding first study 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

Primary outcomes:
measure: Net whole-body protein synthesis
timeFrame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Secondary outcomes:
measure: Citrulline Rate of appearance
timeFrame: Postabsorptive state during 2 hours
measure: Glucose absorption
timeFrame: 7 hours
measure: Gut permeability
timeFrame: 7 hours
measure: Skeletal and respiratory muscle strength
timeFrame: 1 day
measure: Cognitive function
timeFrame: 1 day
measure: Fatty acid digestion after feeding
timeFrame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal
measure: Protein digestion after feeding
timeFrame: 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal
measure: Arginine turnover rate
timeFrame: postabsorptive state during 3 hours
measure: Whole body collagen breakdown rate
timeFrame: Postabsorptive state during 3 hours
measure: Tryptophan turnover rate
timeFrame: Postabsorptive state during 3 hours
measure: Insulin response to feeding
timeFrame: during 3 hours after feeding
measure: Fat-free mass
timeFrame: postabsorptive state during 15 min
measure: Myofibrillar protein breakdown rate
timeFrame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal
measure: Glycine rate of appearance
timeFrame: Postabsorptive state during 3 hours
measure: Taurine turnover rate
timeFrame: postabsorptive state during 3 hours
Other outcomes:
Locations:
city: College Station
country: United States
facility: Texas A&M University
state: Texas
Study officials:
affiliation: Texas A&M Univeristy
name: Marielle PKJ Engelen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wierzchowska-McNew RA, Engelen MPKJ, Thaden JJ, Ten Have GAM, Deutz NEP. Obesity- and sex-related metabolism of arginine and nitric oxide in adults. Am J Clin Nutr. 2022 Dec 19;116(6):1610-1620. doi: 10.1093/ajcn/nqac277.
citation: Pinson MR, Deutz NEP, Harrykissoon R, Zachria AJ, Engelen MPKJ. Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients. BMC Pulm Med. 2021 Nov 7;21(1):351. doi: 10.1186/s12890-021-01719-9.
citation: Engelen MPKJ, Jonker R, Thaden JJ, Ten Have GAM, Jeon MS, Dasarathy S, Deutz NEP. Comprehensive metabolic flux analysis to explain skeletal muscle weakness in COPD. Clin Nutr. 2020 Oct;39(10):3056-3065. doi: 10.1016/j.clnu.2020.01.010. Epub 2020 Jan 29.
citation: Deutz NEP, Thaden JJ, Ten Have GAM, Walker DK, Engelen MPKJ. Metabolic phenotyping using kinetic measurements in young and older healthy adults. Metabolism. 2018 Jan;78:167-178. doi: 10.1016/j.metabol.2017.09.015. Epub 2017 Oct 3.