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

NCT ID: NCT02660437

Last Updated: 2019-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

91 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2018-07-31

Brief Summary

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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).

Detailed Description

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Cerebral Blood Flow (CBF) regulation is crucial for the adequate oxygen supply to the brain and the sustenance of cerebrovascular reserve capacity. A fundamental physiologic regulator of CBF is the carbon dioxide partial pressure (pCO2), which determines the dilatation or contraction of cerebral vasculature. CBF regulation response has been found to be strongly dependent upon pCO2 but much less so upon changes in arterial oxygen saturation. CBF is highly sensitive to pCO2 changes which cause pronounced-vasodilatation in increased pCO2 (CBF augmentation) or vasoconstriction in decreased pCO2 levels (CBF diminution). During cerebral activation and increased metabolism, cerebral arterioles dilate contributing to increase CBF but this process is often challenged during exercise and has a potential impact on cognitive function. CBF is linked to cognitive function while serum level of Brain Derived Neurotrophic Factor (BDNF) has been shown as a critical driving force behind neural plasticity with a potential utility as a biomarker of cognitive decline.

Investigators assume that major pCO2 oscillations during exercise (ΔpCO2 \>4 millimeters of mercury \[mmHg\] from baseline) as a reflection of the abnormality in ventilatory efficiency/drive, lead to overall and local disturbances of cerebral blood flow (CBF) and thus can be associated to increased prevalence of cognitive dysfunction in patients with Chronic Obstructive Pulmonary Disease (COPD). Moreover, investigators hypothesize that patients with major pCO2 oscillations during exercise may develop worse cognitive impairment in several cognitive domains and greater cognitive decline compared to "isocapnic" patients at 6, 12, and 18-month follow-up. Inpatient PR may benefit cognitive function by improving breathing (diminishing pCO2 oscillations), therefore improving CBF, and by increasing cerebral neural activation through exercise.

With regard to cognitive dysfunction, which is associated to increased all-cause mortality and disability, investigators wish:

(A) to detect a relationship between major pCO2 oscillations during exercise and increased prevalence of cognitive dysfunction in COPD; (B) to investigate the impact of different pCO2 transitory-patterns (1. pCO2: decline/ hypocapnic, 2. steady/ isocapnic, 3. increase/ hypercapnic) on CBF regulation and cognitive function; (C) to examine whether major pCO2 oscillations can be a determinant of greater cognitive deterioration in several cognitive domains at 6, 12, and18-month follow-up and (D) to explore the acute effect of 3-week PR on pCO2 oscillations and CBF in respect to cognitive function in COPD patients with cognitive impairment.

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 will be used for measuring cognitive performance (Reaction-Time).

Conditions

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Chronic Obstructive Pulmonary Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Effect of PR in MCI-group

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.

Group Type ACTIVE_COMPARATOR

Pulmonary Rehabilitation program

Intervention Type 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).

Effect of PR in control-group

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.

Group Type PLACEBO_COMPARATOR

Pulmonary Rehabilitation program

Intervention Type 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).

Interventions

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Pulmonary Rehabilitation program

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).

Intervention Type OTHER

Other Intervention Names

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Exercise intervention

Eligibility Criteria

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Inclusion Criteria

* 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 \[mmHg\])

Exclusion Criteria

* 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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Respiratory Society

OTHER

Sponsor Role collaborator

Schön Klinik Berchtesgadener Land

OTHER

Sponsor Role lead

Responsible Party

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Klaus Kenn

Dr. med., Head physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Klaus Kenn, Prof. med.

Role: STUDY_CHAIR

Schön Klinik Berchtesgadener Land

Locations

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Klinikum Berchtesgadener Land der Schön-Kliniken

Schönau am Königssee, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 21483617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25263210 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24782766 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15716851 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10190820 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16443719 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9403456 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22556019 (View on PubMed)

Other Identifiers

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RESPIRE2-8465

Identifier Type: -

Identifier Source: org_study_id

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