Oral Supplement and Acute Resistance Exercise

NCT ID: NCT06801951

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-11
• Study Completion Date: 2020-02-27

Brief Summary

This study should provide the mechanistic basis for and evaluation of a new nutritional formulation to be used alongside exercise training to improve muscle function and exercise performance by minimizing exercise induced metabolic deregulation in patients with Chronic Obstructive Pulmonary Disease.

Detailed Description

Our central hypothesis is that improving the metabolic response to resistance exercise via targeted nutritional modulation with EAA enriched with HMB (EAA+HMB) will increase the gain in muscle function and exercise performance by positively influencing skeletal muscle protein homeostasis among severe COPD patients. Our rationale for the proposed research is that detailed insight in the mechanisms by which resistance exercise induces metabolic deregulations in severe COPD patients, and demonstration of the effectiveness of targeted nutritional intervention will provide opportunities for the development of innovative safe and effective nutritional approaches to improve their training response and skeletal muscle repair, leading to increased daily life physical activity. Furthermore, the proposed studies will provide supportive data of, and focus for a subsequent phase 2b/3 clinical trial to improve quality of life, and clinical outcomes of severe COPD patients. We propose to study simultaneously the following specific aim:

Investigate the metabolic mechanisms by which resistance exercise induces protein catabolism in severe COPD patients as compared to healthy age and gender matched control subjects. Our working hypothesis is that patients with severe COPD (GOLD II-IV) have a metabolic signature that relates to their late (24h) post-exercise catabolic response. We will utilize an innovative IV tracer pulse approach of > 15 labeled amino acids to enable kinetic analysis of their intracellular production, disposal and interconversion rates (fluxomics), and quantify the rates of muscle protein synthesis and breakdown.

The liquid nutrition supplement will be either targeted amino acid formulation (7.0 g EAA and 1.5 g HMB (EAA+HMB)) or placebo (7.0 gram non-essential amino acids). Liquid nutrition supplement will be given to subjects according to a randomized, placebo controlled, double blind, cross-over design.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

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

Study Groups

EAA + HMB

Targeted amino acid formulation (7.0 g EAA and 1.5 g HMB (EAA+HMB))

Group Type: EXPERIMENTAL

acute resistance exercise with oral nutrition supplementation

Intervention Type: OTHER

acute bout of resistance exercise on an isokinetic exercise machine of each limb (i.e., right and left arm and right and left leg) allowing control of velocity and force. Immediately upon completion, 1 serving of liquid nutrition supplement will be consumed. An additional serving of the liquid nutrition supplement will be sent home for consumption in the evening.

stable tracer infusion

Intervention Type: OTHER

stable isotopes Such as L-\[ring-13C6\]-Phenylalanine, L-\[ring-D4\]Tyrosine, L-\[Methyl-D3\]Tau-Methylhistidine, trans-\[2,5,5-D3\]4-Hydroxy-L-proline, L-\[Guanido-15N2\]-Arginine, L-\[4,4,5,5-D4-5-13C\]Citruline, L-13C5 -Ornithine, L-15N2-Glutamine, L-\[1,2-13C2\]Glutamic Acid, 1-13C-Glycine, L-15N3-Histidine, L-13C6-Leucine, L-\[methyl-D3\]Methionine, α-1-13C-ketoisocaproic acid, L-1-13C-Methionine, DL-\[3,3,4,4-D4\]Homocysteine, L-\[1,2-13C2\]Taurine, L-(Indole-D5)Tryptophan, 13C-Urea, L-1-13C-Isoleucine, L-13C5-Valine, α-\[Dimethyl-13C2\]ketoisovaleric acid, 2-keto-3-methyl-13C6-pentanoate, 3-hydroxy-\[3,4-methyl-13C3\]isovaleric acid, 13C3-glycerol is given IV simultaneously

Placebo

7.0 gram non-essential amino acids

Group Type: PLACEBO_COMPARATOR

acute resistance exercise with oral nutrition supplementation

Intervention Type: OTHER

acute bout of resistance exercise on an isokinetic exercise machine of each limb (i.e., right and left arm and right and left leg) allowing control of velocity and force. Immediately upon completion, 1 serving of liquid nutrition supplement will be consumed. An additional serving of the liquid nutrition supplement will be sent home for consumption in the evening.

stable tracer infusion

Intervention Type: OTHER

stable isotopes Such as L-\[ring-13C6\]-Phenylalanine, L-\[ring-D4\]Tyrosine, L-\[Methyl-D3\]Tau-Methylhistidine, trans-\[2,5,5-D3\]4-Hydroxy-L-proline, L-\[Guanido-15N2\]-Arginine, L-\[4,4,5,5-D4-5-13C\]Citruline, L-13C5 -Ornithine, L-15N2-Glutamine, L-\[1,2-13C2\]Glutamic Acid, 1-13C-Glycine, L-15N3-Histidine, L-13C6-Leucine, L-\[methyl-D3\]Methionine, α-1-13C-ketoisocaproic acid, L-1-13C-Methionine, DL-\[3,3,4,4-D4\]Homocysteine, L-\[1,2-13C2\]Taurine, L-(Indole-D5)Tryptophan, 13C-Urea, L-1-13C-Isoleucine, L-13C5-Valine, α-\[Dimethyl-13C2\]ketoisovaleric acid, 2-keto-3-methyl-13C6-pentanoate, 3-hydroxy-\[3,4-methyl-13C3\]isovaleric acid, 13C3-glycerol is given IV simultaneously

Interventions

acute resistance exercise with oral nutrition supplementation

acute bout of resistance exercise on an isokinetic exercise machine of each limb (i.e., right and left arm and right and left leg) allowing control of velocity and force. Immediately upon completion, 1 serving of liquid nutrition supplement will be consumed. An additional serving of the liquid nutrition supplement will be sent home for consumption in the evening.

Intervention Type: OTHER

stable tracer infusion

stable isotopes Such as L-\[ring-13C6\]-Phenylalanine, L-\[ring-D4\]Tyrosine, L-\[Methyl-D3\]Tau-Methylhistidine, trans-\[2,5,5-D3\]4-Hydroxy-L-proline, L-\[Guanido-15N2\]-Arginine, L-\[4,4,5,5-D4-5-13C\]Citruline, L-13C5 -Ornithine, L-15N2-Glutamine, L-\[1,2-13C2\]Glutamic Acid, 1-13C-Glycine, L-15N3-Histidine, L-13C6-Leucine, L-\[methyl-D3\]Methionine, α-1-13C-ketoisocaproic acid, L-1-13C-Methionine, DL-\[3,3,4,4-D4\]Homocysteine, L-\[1,2-13C2\]Taurine, L-(Indole-D5)Tryptophan, 13C-Urea, L-1-13C-Isoleucine, L-13C5-Valine, α-\[Dimethyl-13C2\]ketoisovaleric acid, 2-keto-3-methyl-13C6-pentanoate, 3-hydroxy-\[3,4-methyl-13C3\]isovaleric acid, 13C3-glycerol is given IV simultaneously

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Ability to walk, sit down and stand up independently

Age 45 - 100 years

Willing to lay in bed for 4 hours during study visits

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

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 - 100 years

Willing to lay in bed for 4 hours during long study visits

No diagnosis of COPD

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)

Subjects 86 years and older that fail to get physician eligibility confirmation

Established diagnosis of Insulin dependent diabetes mellitus

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

Use of short course of oral corticosteroids within 4 weeks preceding study day

Dietary or lifestyle characteristics:

Use of protein or amino acid containing nutritional supplements within 5 days of first test day

Indications related to interaction with study products:

Known allergy or sensitivity to milk or milk products

Previous injury that could interfere with participation in resistance exercise protocol

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

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Texas A&M University

OTHER

Sponsor Role: lead

Responsible Party

Marielle PKJ Engelen, PhD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Texas A&M University-CTRAL

College Station, Texas, United States

Countries

United States

Other Identifiers

2017-0655

Identifier Type: -

Identifier Source: org_study_id