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Completed

NCT Number: NCT02660437

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

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).

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Key information

Conditions

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

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Klinikum Berchtesgadener Land der Schön-Kliniken

Schönau am Königssee, 83471, Germany

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

Other names: Exercise intervention

Primary outcomes

  1. Carbon-dioxide partial pressure oscillations (ΔpCO2, mmHg)

    Time frame: Day 4-21

    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).

Secondary outcomes

  1. Cognitive Dysfunction (yes/no)

    Time frame: Day 1-3

    Screening of Cognitive Dysfunction according to Petersen's criteria:

    • Consistent memory complaints preferably corroborated by a close-informant.
    • Objective characterization of specific deficits in memory and/or other cognitive domains, as indicated by a poor performance on MoCA (<26 points), MMSE (<25 points), ACE-R (<88 points) and TICS (<33 points).
    • Preserved ability to perform activities of daily living (ADLs), or minimal impairment if considering instrumental ADLs.
    • Normal global cognitive function.
    • Absence of dementia (Clinical Dementia Rating Scale (CDR ≤1 point)).

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

    Time frame: Day 1-21

    Evaluation of Cognitive Impairment (CI) by the use of clinical instrument of the Standardized Mini-Mental State Examination (SMMSE, scores); 1st measurement prior to the participation in a 3-week (12 sessions) Pulmonary Rehabilitation program (pre-PR); 2nd measurement at the end of PR program (post-PR).

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

    Time frame: Day 1-21

    Evaluation of Cognitive Impairment (CI) by the use of clinical instrument of the Addenbrooke's Cognitive Examination (ACE-R scores); 1st measurement prior to the participation in a 3-week (12 sessions) Pulmonary Rehabilitation program (pre-PR); 2nd measurement at the end of PR program (post-PR).

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

    Time frame: Day 1-21

    Evaluation of Cognitive Impairment (CI) by the use of clinical instrument of the Montreal-Cognitive Assessment (MoCa scores); 1st measurement prior to the participation in a 3-week (12 sessions) Pulmonary Rehabilitation program (pre-PR); 2nd measurement at the end of PR program (post-PR).

  5. Cognitive Impairment (Telephone Interview for Cognitive Status [TICS])

    Time frame: Day 1-21

    Evaluation of Cognitive Impairment (CI) by the use of clinical instrument of the Telephone Interview for Cognitive Status (TICS scores); 1st measurement prior to the participation in a 3-week (12 sessions) Pulmonary Rehabilitation program (pre-PR); 2nd measurement at the end of PR program (post-PR).

  6. Cognitive Performance (Stroop test [reaction-time, seconds])

    Time frame: Day 4-21

    Assessment of cognitive performance (Stroop test - reaction-time, seconds) before and immediately after Cycle-Endurance Test (CET) at 75% of WRpeak. Cognitive performance will be measured by the use of Stroop-test (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).

  7. Cerebral Blood Flow Velocity (CBFv, cm/sec)

    Time frame: Day 4-21

    Measurement of Cerebral Blood Flow velocity (CBFv, cm/sec) as surrogate of Cerebral Blood Flow (CBF) before and immediately after Cycle-Endurance Test (CET) at 75% of WRpeak. Cerebral Blood Flow velocity (CBFv) will be measured by the use of transcranial Doppler ultrasonography (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).

  8. Frontal cortex cerebrovascular oxygen saturation (Tissue Oxygen Saturation [TOI, %])

    Time frame: Day 4-21

    Measurement Tissue Oxygen Saturation (TOI, %) as an index of frontal cortex cerebrovascular oxygen saturation during Cycle-Endurance Test (CET) at 75% of WRpeak. Tissue oxygen saturation (TOI, %) will be continuously measured by the use of Near-Infrared Spectroscopy (NIRS-method; pre/post measurement): 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).

  9. Frontal cortex cerebrovascular oxygen saturation (Changes in Deoxygenated Haemoglobin [ΔHHb, μM/cm])

    Time frame: Day 4-21

    Measurement of the changes in Deoxygenated Haemoglobin (ΔHHb) in micrometer per centimeter (μM/cm) as an index of frontal cortex cerebrovascular oxygen saturation during Cycle-Endurance Test (CET) at 75% of WRpeak. Changes in Deoxygenated Haemoglobin (ΔHHb, μM/cm) will be continuously measured by the use of Near-Infrared Spectroscopy (NIRS-method; pre/post measurement): 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).

Other outcomes

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

    Time frame: Day 1-4

    Measurement of Forced Expiratory Pressure in 1 Second (FEV1, %predicted).

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

    Time frame: Day 1-6

    Measurement of exercise capacity by a cardiopulmonary exercise test (CPET) on cycle ergometer using an incremental protocol to the limit of tolerance (peak Work Rate, watts)) for establishing the work rate corresponding to 75% of peak (maximum working capacity) according to the international guidelines.

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

    Time frame: Day 1-6

    Measurement of arterial oxygen partial pressure (PaO2, mmHg) in blood samples.

  4. Blood Gas Analyses (Arterial carbon-dioxide partial pressure [PaCO2, mmHg])

    Time frame: Day 1-6

    Measurement of arterial carbon-dioxide partial pressure (PaCO2, mmHg) in blood samples.

  5. Brain Derived Neurotrophic Factor (BDNF serum levels, ng/mL).

    Time frame: Day 1-8

    Measurement of serum levels of Brain Derived Neurotrophic Factor (BDNF, ng/mL) in blood samples.

  6. Psychological condition/ Psychological data (Hospital Anxiety and Depression Scale [HADS, scores])

    Time frame: Day 5-8

    Psychological factors will be assessed by the use of the Hospital Anxiety and Depression Scale (HADS).

  7. Psychological condition/ Psychological data (COPD Assessment Test [CAT, scores])

    Time frame: Day 5-8

    Psychological factors will be assessed by the use of the COPD Assessment Test (CAT).

  8. Psychological condition/ Psychological data (St. George Respiratory Questionnaire [SGRQ, scores])

    Time frame: Day 5-8

    Psychological factors will be assessed by the use of the St. George Respiratory Questionnaire (SGRQ).

  9. Perception of Dyspnoea (Medical Research Council dyspnoea scale, [MRC scores])

    Time frame: Day 5-8

    Perception of dyspnoea will be assessed by the use of the Medical Research Council (MRC) dyspnoea scale.

Sponsors and collaborators

Lead sponsor

Schön Klinik Berchtesgadener Land

Other

Collaborators

  • European Respiratory Society

Registry information

Official study title

Carbon Dioxide Partial Pressure Oscillations During Exercise: Relation to Cerebral Blood Flow Regulation and and to the Prevalence of Cognitive Dysfunction in COPD

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Jan 21, 2016
Registry last updated
Feb 28, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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