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For this study a resistance bout will be performed in order to promote the robust response of protein synthesis. Type II muscle fibers often exhibit more atrophy than type I fibers in COPD subjects therefore specifically targeting them in an exercise protocol could have more beneficial outcome for these individuals.
In this study, the following hypothesis will be tested: A bout of resistance exercise will affect the acute and 24h response in whole-body protein and amino acid metabolism and cognitive function as compared to baseline values in COPD patients and healthy subjects. To do this, subjects will complete a baseline visit in which they receive stable amino acid tracers. The next day they will complete a one-time resistance exercise with an immediate measurement of the amino acid tracers, and return 24 hours after exercise to repeat amino acid tracer measurements. This project will provide important clinical information on the whole body protein and amino acid metabolic response to acute resistance exercise in elderly subjects with COPD, as well as, the exercise induced changes in physical and cognitive function, and absolute muscular strength capacity in this population. In this way, this study will provide preliminary data for the development of standardized, repeatable resistance exercise protocols that will stop the process of ongoing muscle loss and improve metabolism and function in COPD subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy | Experimental | screening visit: body weight and composition by DXA, height, and vital signs will be assessed. study day(s): may include combinations of stable isotope infusions with blood draws, acute exercise, cognition testing |
|
| Chronic Obstructive Pulmonary Disorder | Experimental | screening visit: body weight and composition by DXA, height, and vital signs will be assessed. study day(s): may include combinations of stable isotope infusions with blood draws, acute exercise, cognition testing |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| stable amino acid infusion | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in net whole-body protein synthesis | Change in whole-body protein synthesis rate | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| glutamate related metabolism | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes | |
| tryptophan related metabolism | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes |
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Inclusion criteria COPD subjects:
Inclusion criteria healthy subjects:
Exclusion Criteria all subjects:
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| Name | Affiliation | Role |
|---|---|---|
| Marielle Engelen, PhD | Texas A&M University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texas A&M University-CTRAL | College Station | Texas | 77845-4253 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40233541 | Derived | Sontam T, Deutz NEP, Cruthirds CL, Mbilinyi R, Ruebush LE, Ten Have GA, Thaden JJ, Engelen MPKJ. Prolonged disturbances in citrulline metabolism following resistance exercise in COPD. Clin Nutr. 2025 Jun;49:21-32. doi: 10.1016/j.clnu.2025.03.021. Epub 2025 Apr 8. | |
| 40113079 | Derived | Mbilinyi RH, Deutz NEP, Cruthirds CL, Ruebush LE, Sontam T, Ten Have GAM, Thaden JJ, Engelen MPKJ. Prolonged increase in glutamate whole body and intracellular production in older adults with COPD and healthy controls post-resistance exercise. Metabolism. 2025 Jul;168:156185. doi: 10.1016/j.metabol.2025.156185. Epub 2025 Mar 18. |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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|
| acute exercise with amino acid infusion | Other | resistance exercise of each limb (i.e., leg (right/left); arm (right/left) on an isokinetic exercise machine allowing control of velocity, force, etc. with 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 |
|
| 24-hour post exercise amino acid infusion | 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 |
|
| arginine related metabolism | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes |
| leucine related metabolism | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes |
| taurine related metabolism | 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210 and 240 ± 5 minutes |
| Body Composition | Body composition as measured by Dual-Energy X-ray Absorptiometry | 15 minutes on screening or study day 1 |
| changes in skeletal muscle fatigue | kin-com 1-leg test | on study day 1 and change from day 2 and day 3 |
| Group differences in state of mood as measured by the Hospital Anxiety and Depression Scale (HADS) | a fourteen item self-assessment scale. Seven of the items related to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. | 1 day |
| Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT) | a word page with words printed in black ink, a color page with blocks printed in color, and a color-word page where the color and the word do not match. The examinee reads the words or names the ink colors as quickly as possible within a time limit. Measures selective attention and inhibitory control. The total time in seconds was reported for each trial. | on study day 1 and change from day 2 and day 3 |
| Group differences in learning and memory as measured by Digit Span | recall of numbers in the same order (Digit Forward) and in reverse order (Digit Backward). Measures auditory attention and verbal working memory. | on study day 1 and change from day 2 and day 3 |
| Group differences in attention and executive functions as measured by Digit Symbol Modalities Test | Using a legend with nine symbols that correspond to nine different numbers, the examinee is asked to fill in as many blank squares as possible by copying the corresponding number in each box, indexed by a symbol within a 90 sec time limit. | on study day 1 and change from day 2 and day 3 |
| Group differences in activity as measured by Physical Activity Scale for the Elderly (PASE) | This questionnaire is intended for use in an elderly population and focuses on 3 types of activities: leisure time activities, household activities and work-related activities. | study day 1 |
| 24 hour diet recall | The subject is asked to recall in detail all the food and drink consumed during the 24 hours prior to the test day. | study day 1 |
| appetite questionnaire | The subject is asked to rate various aspects of their appetite as relates to overall health | study day 1 |
| 38616018 | Derived | Deutz LN, Wierzchowska-McNew RA, Deutz NE, Engelen MP. Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity? Am J Clin Nutr. 2024 Jun;119(6):1455-1464. doi: 10.1016/j.ajcnut.2024.04.008. Epub 2024 Apr 12. |
| 37542951 | Derived | Engelen MPKJ, Kirschner SK, Coyle KS, Argyelan D, Neal G, Dasarathy S, Deutz NEP. Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease. Clin Nutr. 2023 Sep;42(9):1737-1746. doi: 10.1016/j.clnu.2023.06.031. Epub 2023 Jul 26. |
| 36166849 | Derived | 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. |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |