Nutritional and Functional Changes in Heart Failure and COPD

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metabolic and Functional Changes in Relation to Nutritional Status in Chronic Heart Failure and Chronic Obstructive Pulmonary Disorder

Conditions
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Chronic Heart Failure, Chronic Obstructive Pulmonary Disorder

Intervention / Treatment
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* Dietary Supplement: BOOST High Protein


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boost High Protein<br>Boost high protein with added spirulina | Dietary Supplement: BOOST High Protein<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net whole-body protein synthesis | change in whole-body protein synthesis rate after intake of meal | 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Citrulline Rate of appearance | plasma enrichment of citrulline | Postabsorptive state during 2 hours | 
| Glucose absorption | Recovery of 3-O-Methyl-D-glucose in the urine. | 7 hours | 
| Gut permeability | recovery of rhamnose/lactulose in urine | 7 hours | 
| Skeletal and respiratory muscle strength | Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between heart failure patients and healthy controls. | 1 day | 
| Cognitive function | Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism | 1 day | 
| Fatty acid digestion after feeding | Enrichment in palmitic acid and tripalmitin fatty acids in plasma | 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal | 
| Protein digestion after feeding | Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina | 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal | 
| Arginine turnover rate | Arginine enrichment in plasma | postabsorptive state during 3 hours | 
| Whole body collagen breakdown rate | Hydroxyproline enrichment in plasma | Postabsorptive state during 3 hours | 
| Tryptophan turnover rate | Tryptophan enrichment in plasma | Postabsorptive state during 3 hours | 
| Insulin response to feeding | Acute change from postabsorptive state after intake of meal | during 3 hours after feeding | 
| Fat-free mass | Characteristics of study subjects | postabsorptive state during 15 min | 
| Myofibrillar protein breakdown rate | 3methylhistidine enrichment in plasma | 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal | 
| Glycine rate of appearance | glycine enrichment in plasma | Postabsorptive state during 3 hours | 
| Taurine turnover rate | enrichment of taurine in | postabsorptive state during 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHF, Protein digestion, Fat digestion, Gut function, Glucose absorption, Muscle function