pCO2 Oscillations During Exercise: Relation to Cerebral Blood Flow and to Cognitive Dysfunction in COPD

NCT02660437 | Completed

• 1 other identifier: RESPIRE2-8465
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators wish to identify a relationship between substantial changes in carbon dioxide partial-pressure (pCO2), which frequently occur during the transitions from rest to exercise (ΔpCO2 \>4 millimeters of mercury \[mmHg\] from baseline), and the prevalence of cognitive dysfunction in COPD. In particular, it is anticipated to investigate the vascular effect of pCO2 oscillations in the regulation of cerebral blood flow (CBF) during exercise and its impact on cognitive function in Chronic Obstructive Pulmonary Disease (COPD). Furthermore, this study aims to examine whether major pCO2 oscillations have prognostic value in cognitive deterioration at 6, 12, and 18-month follow-up. In addition, the acute effect of 3-week pulmonary rehabilitation (PR) on cognitive function will be explored. The evaluation of cognitive function will be performed by the use of Standardized Mini Mental State Examination (SMMSE), Addenbrooke's Cognitive Examination (ACE-R), Montreal Cognitive Assessment (MoCA), and Telephone Interview for Cognitive Status (TICS) assessing several cognitive domains (cognitive scores) whereas Stroop test \[color reading interference\] will be used for measuring cognitive performance (Reaction-Time).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Carbon dioxide partial pressure (pCO2); Cerebral blood flow (CBF); Cognitive dysfunction; Mild/Moderate Cognitive Impairment (MCI); Pulmonary Rehabilitation (PR); Standardized Mini Mental State Examination (SMMSE); Addenbrooke's Cognitive Examination (ACE-R); Montreal Cognitive Assessment (MoCA); Telephone Interview for Cognitive Status (TICS); Stroop test (Reaction Time)

Outcome Measures

Primary Outcomes (1)

• Carbon-dioxide partial pressure oscillations (ΔpCO2, mmHg)

  Changes in transcutaneous pCO2 (ΔpCO2, mmHg from baseline values) during Cycle-Endurance Test (CET) at 75% of peak Work Rate (WRpeak). The pCO2 oscillations will be transcutaneous monitored and continuously recorded by the use of "SenTec" Digital Monitoring System (pre/post measurements): 1st measurement during a CET prior to the participation in a 3-week (12 sessions) Pulmonary Rehabilitation program (pre-PR); 2nd measurement during a CET at the end of PR program (post-PR).

  Day 4-21

Secondary Outcomes (9)

• Cognitive Dysfunction (yes/no)

  Day 1-3

• Cognitive Impairment (Standardized Mini-Mental State Examination [SMMSE, scores])

  Day 1-21

• Cognitive Impairment (Addenbrooke's Cognitive Examination [ACE-R])

  Day 1-21

• Cognitive Impairment (Montreal-Cognitive Assessment [MoCA, scores])

  Day 1-21

• Cognitive Impairment (Telephone Interview for Cognitive Status [TICS])

  Day 1-21

Other Outcomes (9)

• Airflow limitation (Forced Expiratory Pressure in 1 Second [FEV1, %predicted])

  Day 1-4

• Exercise capacity (peak Work Rate, [WRpeak watts])

  Day 1-6

• Blood Gas Analyses (Arterial oxygen partial pressure [PaO2, mmHg])

  Day 1-6

Study Arms (2)

Effect of PR in MCI-group

ACTIVE COMPARATOR

Evaluation of the acute effect of a 3-week Pulmonary Rehabilitation (PR) program in cognitive function of MCI-Group using SMMSE, ACE-R, MoCA, TICS and Stroop test clinical instruments in reference to potential changes in pCO2 oscillation patterns (post-PR). Intervention: Pulmonary Rehabilitation program; 12 sessions of exercise training/breathing techniques.

Other: Pulmonary Rehabilitation program

Effect of PR in control-group

PLACEBO COMPARATOR

Evaluation of the acute effect of a 3-week Pulmonary Rehabilitation (PR) program in cognitive function of control-group using SMMSE, ACE-R, MoCA, TICS and Stroop test clinical instruments in reference to potential changes in pCO2 oscillation patterns (post-PR). Intervention: Pulmonary Rehabilitation program; 12 sessions of exercise training/breathing techniques.

Other: Pulmonary Rehabilitation program

Interventions

Pulmonary Rehabilitation program OTHER

Patients will attend a comprehensive 3-week PR program (12sessions/ 60min·day) including high intensive interval exercise equivalent to 100% of peak work rate (WRpeak) with 30sec work periods interspersed with 30sec rest periods for 30min and light resistance training (3muscle groups/ 4sets each/10repetitions; \~30min).

Also known as: Exercise intervention

Effect of PR in MCI-group; Effect of PR in control-group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Chronic Obstructive Pulmonary Disease (COPD) in Global Initiative on Obstructive Lung Disease (GOLD) stages II to IV
• COPD patients with mild to moderate cognitive impairment (MCI-group: n=100) and without cognitive impairment (Control-group: n=60)
• Normotensive (Blood Pressure range: 101-143/62-91 millimeters of mercury \[mmHg\])

You may not qualify if:

• Resting partial pressure of oxygen in arterial blood (paO2) \<55 millimeters of mercury \[mmHg\]
• Resting partial pressure of carbon dioxide in arterial blood (paCO2) \>45 millimeters of mercury \[mmHg\]
• last exacerbation ≤4weeks
• severe cognitive impairment/dementia
• other neuropsychiatric symptoms

Sponsors & Collaborators

• Schön Klinik Berchtesgadener Land: lead
• European Respiratory Society: collaborator

Study Sites (1)

Klinikum Berchtesgadener Land der Schön-Kliniken

Schönau am Königssee, 83471, Germany

Location

Related Publications (8)

• Payne SJ, Mohammad J, Tisdall MM, Tachtsidis I. Effects of arterial blood gas levels on cerebral blood flow and oxygen transport. Biomed Opt Express. 2011 Mar 25;2(4):966-79. doi: 10.1364/BOE.2.000979.

  PMID: 21483617 BACKGROUND

• Ogoh S, Tsukamoto H, Hirasawa A, Hasegawa H, Hirose N, Hashimoto T. The effect of changes in cerebral blood flow on cognitive function during exercise. Physiol Rep. 2014 Sep 28;2(9):e12163. doi: 10.14814/phy2.12163. Print 2014 Sep 1.

  PMID: 25263210 BACKGROUND

• Shimada H, Makizako H, Doi T, Yoshida D, Tsutsumimoto K, Anan Y, Uemura K, Lee S, Park H, Suzuki T. A large, cross-sectional observational study of serum BDNF, cognitive function, and mild cognitive impairment in the elderly. Front Aging Neurosci. 2014 Apr 15;6:69. doi: 10.3389/fnagi.2014.00069. eCollection 2014.

  PMID: 24782766 BACKGROUND

• Ito H, Ibaraki M, Kanno I, Fukuda H, Miura S. Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. J Cereb Blood Flow Metab. 2005 Jul;25(7):852-7. doi: 10.1038/sj.jcbfm.9600076.

  PMID: 15716851 BACKGROUND

• Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999 Mar;56(3):303-8. doi: 10.1001/archneur.56.3.303.

  PMID: 10190820 BACKGROUND

• Van der Elst W, Van Boxtel MP, Van Breukelen GJ, Jolles J. The Stroop color-word test: influence of age, sex, and education; and normative data for a large sample across the adult age range. Assessment. 2006 Mar;13(1):62-79. doi: 10.1177/1073191105283427.

  PMID: 16443719 BACKGROUND

• Valdueza JM, Balzer JO, Villringer A, Vogl TJ, Kutter R, Einhaupl KM. Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography. AJNR Am J Neuroradiol. 1997 Nov-Dec;18(10):1929-34.

  PMID: 9403456 BACKGROUND

• Vogiatzis I, Louvaris Z, Habazettl H, Andrianopoulos V, Wagner H, Roussos C, Wagner PD, Zakynthinos S. Cerebral cortex oxygen delivery and exercise limitation in patients with COPD. Eur Respir J. 2013 Feb;41(2):295-301. doi: 10.1183/09031936.00016312. Epub 2012 May 3.

  PMID: 22556019 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Klaus Kenn, Prof. med.

  Schön Klinik Berchtesgadener Land

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med., Head physician

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 21, 2016
• Study Start: March 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: July 1, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)