Physical Exercise and Responses Measured by HIF-1 in COPD

NCT04955977 | Unknown

• 1 other identifier: 47970
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Despite being considered a potentially preventable disease, COPD is classified as one of the respiratory problems with the highest prevalence and socioeconomic impact. According to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD), people with COPD require actions that optimize quality of life by improving lung function and increasing tolerance to fatigue. Research such as those carried out by Semenza, establish that metazoan organisms such as the human species present biomolecular mechanisms for O2 homeostasis, based on transcriptional changes that allow regulating or modifying the responses necessary for the maintenance of the cellular metabolic functions. Hypoxia Induced Factor 1 (HIF-1) is the primary molecular mechanism for the regulation of O2-regulated genes in nuclear cells; Therefore, they promote adaptive mechanisms to hypoxia, through the generation of protein synthesis that favor processes such as erythropoiesis, angiogenesis, changes in oxidative metabolism and modification of the pulmonary vascular response. Research carried out in cells of people with COPD exposed to environmental hypoxia by low oxygen pressure (PO2), have shown changes in the nuclear concentrations of HIF-1, affecting the transcriptional mechanisms of specific genes for Erythropoietin (EPO), the Factor of Vascular Endothelial Growth (VEFG) and therefore limit the generation of essential proteins for systemic responses. These transcriptional mechanisms are conditioned by the structural changes of chromatin seconded by the inhibition in the performance of histone enzymes, which influences the synthesis of proteins involved in metabolic, hematological and / or ventilatory processes as a response. to hypoxia. However, the concentration and effect of HIF 1 on the synthesis of EPO and VEGF and its relationship with spirometric and hematological tests have not been studied in COPD people who live in medium altitudes and who are additionally exposed to additional hypoxic stimuli such as exercise physical. Although it is known that in COPD there is a decrease in the diffusion of O2 through the blood-gas barrier generating hypoxia and that with low PO2 there are biomolecular adaptations to favor oxygenation, perfusion, and metabolism; At the moment, the responses of HIF-1 and its effect on the generation of proteins associated with erythropoiesis and angiogenesis (EPO, FEVG) in people with COPD with physical exercise-based treatments are unknown.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Exercise; Hypoxia; Epigenomics; Therapeutics

Outcome Measures

Primary Outcomes (3)

• Nuclear concentration of HIF-1

  Changes in the nuclear concentration of hypoxia-inducible factor (HIF-1) in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• VEGF protein synthesis.

  Changes in the synthesis of the Vascular Endoletial Growth Factor (VEGF) protein in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• Synthesis of EPO protein.

  Changes in the synthesis of Erythropoietin (EPO) protein synthesis in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

Secondary Outcomes (13)

• Arm Curl Test

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• Chair Stand Test

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• 6 Minute WalK Test

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• Chair-Sit and Reach Test

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

• Back Scratch Test

  1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.

Study Arms (3)

G1: People with a diagnosis of COPD stratified in GOLD 1-2.

EXPERIMENTAL

* Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years. * People with a diagnosis of COPD categorized in GOLD 1-2, with no record of respiratory crises in the last 3 months. * People with a diagnosis of COPD categorized by lung function in GOLD 1,2,3 and 4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen. * People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l. * People who have read and signed informed consent and who have membership in a mandatory health plan.

Other: Physical exercise program; Other: Health education in COPD

G2: People with a diagnosis of COPD stratified in GOLD 3-4.

EXPERIMENTAL

* Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years. * People with a diagnosis of COPD categorized in GOLD 1,2,3 and 4, with no record of respiratory crises in the last 3 months. * People with a diagnosis of COPD categorized by lung function in GOLD 3-4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen. * People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l. * People who have read and signed informed consent and who have membership in a mandatory health plan.

Other: Physical exercise program; Other: Health education in COPD

G3: Control - People without a COPD diagnosis.

ACTIVE COMPARATOR

Healthy people, over 40 years old. No history of cigarette smoking or exposure to wood smoke. Who do not present diagnoses of musculoskeletal injuries and who are residents at 2600 meters above sea level for more than 14 months. With affiliation to a mandatory health plan and signature of informed consent.

Other: Physical exercise program

Interventions

Physical exercise program OTHER

Step 1 • Diaphragmatic reeducation: • Aerobic capacity: Intensity: zone 2, 60% HRMax, 4-6 / 10 Borg Scale; Charge: 20 m. Step 2 • Aerobic capacity: Intensity: zone 2, 65% HRMax, 4-6 Borg Scale; Charge: 25 m. • Muscular strength: Method: Pyramidal; Intensity: 3-4 / 10 Omni-Res; Load: 20% 1RM; Series: 3; Reps: 1. • Flexibility and elasticity: Intensity: 31-60 Perflex Scale; Charge: 10 - 20 s. Step 3 • Aerobic capacity: Intensity: zone 3, 70% HRMax, 5-6 / 10 Borg scale, Load: 25 m. • Muscular strength: Method: Pyramidal; Intensity: 4-5 / 10 Omni-Res; Load: 30% 1RM; Series: 4; Reps: 10. • Flexibility and elasticity: Method: active stretching; Intensity: 31-60 Perflex Scale; Charge: 10 - 20 s. Step 4 •Aerobic capacity: Intensity: zone 3, 75% HRMax, 6-7 / 10 Borg scale, Load: 30 m. • Muscular strength: Intensity: 5-6 / 10 Omni-Res; Load: 40-50% 1RM; Series: 4 s; Reps: 13. • Flexibility and elasticity: Method: active stretching; Intensity: 31-60 Perflex Scale; Charge: 10 - 20 s.

Also known as: Therapeutic exercise

G1: People with a diagnosis of COPD stratified in GOLD 1-2.; G2: People with a diagnosis of COPD stratified in GOLD 3-4.; G3: Control - People without a COPD diagnosis.

Health education in COPD OTHER

Week 1-2: Health education: COPD and respiratory care at home. Week 3-4: Importance of daily physical activity in COPD. Week 5-6: Early Signs of COPD Exacerbation and Action Plan Week 7-8: Use and care of respiratory devices at home.

Also known as: Health education

G1: People with a diagnosis of COPD stratified in GOLD 1-2.; G2: People with a diagnosis of COPD stratified in GOLD 3-4.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
• People with a diagnosis of COPD categorized in GOLD 1,2,3 and 4, with no record of respiratory crises in the last 3 months.
• People with a diagnosis of COPD categorized by lung function in GOLD 1,2,3 and 4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
• People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
• People who have read and signed informed consent and who have membership in a mandatory health plan.

You may not qualify if:

• People with a medical diagnosis of anemia, liver disease, chronic kidney disease, rheumatological diseases or a history of gastrointestinal bleeding in the last 2 months.
• People with a diagnosis of COPD who have a history of kidney or liver transplantation.
• People with a diagnosis of COPD who present severity of symptoms and/or respiratory exacerbations categorized in D presenting an mMRC \> 2 and CAT \> 10 with \>1 hospitalization requirements.
• People who are under pharmacological management with erythropoietin (EPO), antibiotics and / or steroids on a chronic basis.
• People with musculoskeletal injuries that limit the execution of the physical training program or that present medical restrictions for the execution of physical exercise.
• People with a diagnosis of COPD who record active smoking.
• People who are participating in research related to medical, pharmacological or physiotherapeutic intervention protocols.

Sponsors & Collaborators

• Universidad Nacional de Colombia: lead
• University of Barcelona: collaborator

Study Sites (1)

National university of Colombia

Bogotá, Cundinamarca, 110821, Colombia

RECRUITING

Related Publications (9)

• Lee SW, Hwang HH, Hsu PW, Chuang TY, Liu CW, Wu LS. Whole-genome methylation profiling from PBMCs in acute-exacerbation COPD patients with good and poor responses to corticosteroid treatment. Genomics. 2019 Dec;111(6):1381-1386. doi: 10.1016/j.ygeno.2018.09.010. Epub 2018 Sep 21.

  PMID: 30248490 BACKGROUND

• To M, Yamamura S, Akashi K, Charron CE, Haruki K, Barnes PJ, Ito K. Defect of adaptation to hypoxia in patients with COPD due to reduction of histone deacetylase 7. Chest. 2012 May;141(5):1233-1242. doi: 10.1378/chest.11-1536. Epub 2011 Dec 15.

  PMID: 22172637 BACKGROUND

• Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 2005 May 12;352(19):1967-76. doi: 10.1056/NEJMoa041892.

  PMID: 15888697 BACKGROUND

• Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE. 2007 Oct 9;2007(407):cm8. doi: 10.1126/stke.4072007cm8.

  PMID: 17925579 BACKGROUND

• Fu X, Zhang F. Role of the HIF-1 signaling pathway in chronic obstructive pulmonary disease. Exp Ther Med. 2018 Dec;16(6):4553-4561. doi: 10.3892/etm.2018.6785. Epub 2018 Sep 21.

  PMID: 30542404 BACKGROUND

• Chen LJ, Xu W, Li YP, Ma LT, Zhang HF, Huang XB, Yu GG, Ma XQ, Chen C, Liu YH, Wu J, Wang LJ, Xu Y. Lycium barbarum Polysaccharide Inhibited Hypoxia-Inducible Factor 1 in COPD Patients. Int J Chron Obstruct Pulmon Dis. 2020 Aug 24;15:1997-2004. doi: 10.2147/COPD.S254172. eCollection 2020.

  PMID: 32921997 BACKGROUND

• Kanazawa H, Yoshikawa J. Elevated oxidative stress and reciprocal reduction of vascular endothelial growth factor levels with severity of COPD. Chest. 2005 Nov;128(5):3191-7. doi: 10.1378/chest.128.5.3191.

  PMID: 16304261 BACKGROUND

• Tao H, Luo W, Pei H, Zhu S, Zhang M, Chen B, He J, Zhang M, Zhou R. [Expression and significance of hypoxia-inducible factor-1alpha in patients with chronic obstructive pulmonary disease and smokers with normal lung function]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014 Aug;30(8):852-5. Chinese.

  PMID: 25108440 RESULT

• Villamil-Parra W, Cristancho-Mejia E, Ramon Torrella J, Mancera-Soto EM. Effects of a physical exercise program on HIF-1alpha in people with Chronic Obstructive Pulmonary Disease living at high altitude: study protocol for a clinical trial. Trials. 2023 Oct 29;24(1):698. doi: 10.1186/s13063-023-07698-y.

  PMID: 37899477 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Motor Activity; Hypoxia

Interventions

Exercise Therapy

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• Wilder A Villamil-Parra, Therapist

  Universidad Nacional de Colombia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wilder A Villamil-Parra, Therapist

CONTACT

(57)3017564038; wavillamilp@unal.edu.co

Erica M Mancera-Soto, Therapist

CONTACT

emmanceras@unal.edu.co

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Unique masking when study participants, who will not know: 1. Assignment to research groups, for which the measurement of the severity of the disease will be developed individually. 2. Treatment to receive, for which the intervention will be carried out individually and at the home of each participant.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Quasi-experimental study with assignment to groups by convenience by severity of the disease. Group 1: COPD GOLD1-2, Group 2: COPD GOLD3-4, Group 3: Control. Study with intra- and inter-group comparison before and after intervention with an external control group

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 9, 2021
• Study Start: January 1, 2022
• Primary Completion: March 1, 2022
• Study Completion: June 1, 2022
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)