Clinical trial NCT02770092: CHF COPD Sip Feed Anabolic Response
Official title: Anabolic Responsiveness to Protein Intake in Chronic Heart Failure and Chronic Obstructive Pulmonary Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Congestive Heart Failure
Lead sponsor: Texas A&M University
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 150
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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 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.

Detailed description: General aims:

* To study the whole-body protein anabolic effect of several dosages of a high-quality protein sip feeding in COPD and CHF subjects as compared to healthy controls.
* To investigate the anabolic threshold in subjects with COPD and CHF as compared to healthy controls.

Purpose and objectives: Although the Researchers' previous study supports the concept of supplementing high-quality milk proteins in chronic wasting diseases i.e., COPD and CHF, the dose-response anabolic effects of proteins with high EAA levels are still unclear. Furthermore, there is no insight in the actual protein requirements in COPD and CHF. The knowledge gained from this study will benefit insight in terms of promotion of protein gain after feeding in COPD and CHF subjects. Based on the obtained data of protein behavior (protein kinetics) the Researchers will be able to further refine and personalize nutritional supplementation in COPD and CHF subjects in order to stop and even restore progressive muscle wasting.

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 8 hours
* Diagnosis of CHF; under regular care by cardiologist
* Reduced ejection fraction (\<45%) assessed in the past 2 years
* NYHA class II-IV
* 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 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 8 hours
* No diagnosis of CHF or COPD
* Willingness and ability to comply with the protocol

Exclusion Criteria all subjects:

* Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only)
* Established diagnosis of malignancy
* 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
* Already enrolled in another clinical trial and that clinical trial interferes with participating in this study

When during the period from enrollment to the test day any condition causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study.

Primary outcomes:
measure: Change in net whole-body protein synthesis
timeFrame: 0, 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 225, 240, 260, 280, 300, 320, 340, 360 ± 5 min
Secondary outcomes:
measure: Body Composition
timeFrame: 15 minutes on screening or study day 1
measure: Skeletal muscle strength
timeFrame: on study day 1
measure: Respiratory muscle strength
timeFrame: on study day 1
measure: Gut function
timeFrame: In postabsorptive and prandial state every 20 minutes up to 6 hours before each sip feeding on study day
measure: Group differences in state of mood as measured by the Hospital Anxiety and Depression Scale (HADS)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Executive Function-Adolescent/Adult Sensory Profile (ASP):
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in quality of life as measured by Short Form (36) Health Survey (SF36)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in activity as measured by Physical Activity Scale for the Elderly (PASE)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT),
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in state of mood as measured by the Profile of Mood State (POMS)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in learning and memory as measured by Controlled Oral Word Association Test (COWAT),
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in learning and memory as measured by Auditory Verbal Learning Test (AVLT)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in attention and executive functions as measured by PASAT
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in attention and executive functions as measured by Trail Making Test (TMT)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in overall cognitive abilities as measured by Montreal Cognitive Assessment (MoCA)
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: Group differences in attention and executive functions as measured by Brief-A
timeFrame: Postabsorptive state during 3 hours and change after feeding on study day 1
measure: diet recall
timeFrame: on study day 1
Other outcomes:
Locations:
city: College Station
country: United States
facility: Texas A&M University-CTRAL
state: Texas
Study officials:
affiliation: Study Principal Investigator
name: Marielle Engelen
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: Deutz NEP, Singer P, Wierzchowska-McNew RA, Viana MV, Ben-David IA, Pantet O, Thaden JJ, Ten Have GAM, Engelen MPKJ, Berger MM. Comprehensive metabolic amino acid flux analysis in critically ill patients. Clin Nutr. 2021 May;40(5):2876-2897. doi: 10.1016/j.clnu.2021.03.015. Epub 2021 Mar 18.