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Trial record 27 of 54 for:    COPD OR COPD OR chronic obstructive pulmonary disease OR chronic bronchitis OR emphysema | Recruiting, Not yet recruiting, Available Studies | NIH, U.S. Fed

COPD-Related Physiology and the Brain

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ClinicalTrials.gov Identifier: NCT03269721
Recruitment Status : Recruiting
First Posted : September 1, 2017
Last Update Posted : April 3, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Karin Hoth, University of Iowa

Brief Summary:
COPD is the third leading cause of combined morbidity, disability, and mortality in the United States and is often associated with cognitive impairment. The goal of the proposed project is to examine novel pulmonary and vascular physiological mechanisms that contribute to structural brain abnormalities and cognitive dysfunction early in the course of COPD. The project will generate information to ultimately inform the development of interventions to delay or prevent cognitive dysfunction.

Condition or disease Intervention/treatment
Pulmonary Disease, Chronic Obstructive (COPD) Cognitive Impairment Behavioral: Neuropsychological Assessment Procedure: Spirometry Procedure: Arterial Blood Gas Procedure: Diffusion Capacity of the Lung for Carbon Monoxide Diagnostic Test: 6 Minute Walk Test Procedure: Systemic Vascular Measures Biological: Blood Biomarkers Behavioral: Symptom Questionnaire Measures Procedure: Brain MRI

Detailed Description:
Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of morbidity and mortality in the US with increasing prevalence in older adults. The impact of COPD on the brain is an area of expanding research interest. A staggering 40-60% of patients with COPD have cognitive impairments including deficits in executive functioning (e.g., decision making), processing speed, and memory. Intact cognition is critical for independently managing daily tasks (e.g., medication and money management). Since there are currently no treatments to fully reverse cognitive impairment once it is present, preventing and delaying onset is essential. Given the high prevalence of COPD, understanding how COPD confers an increased risk for cognitive impairment should be a top public health priority. There is an urgent need to identify potentially modifiable physiological characteristics of individuals with early COPD-related pathophysiology who are at risk of developing brain abnormalities. The earliest changes that occur in COPD are driven by an enhanced chronic inflammatory response that includes small airway disease in the lung and vascular abnormalities. COPD-related lung pathophysiology can be measured continuously and is separable from amount of smoking. These physiological changes are often present in individuals who do not meet traditional criteria for COPD diagnosis and have not yet manifested significant clinical symptoms. We propose that chronic smokers who are susceptible to COPD and show evidence of COPD-related lung pathophysiology on lung CT also experience vascular dysfunction (particularly central artery stiffness) that contributes to structural brain abnormalities and cognitive impairment. The proposed project will: 1) model the effects of novel physiological mechanisms on the brain in COPD, 2) focus on changes in brain structure and function early in the development of COPD by including smokers who have evidence of early COPD-related lung pathophysiology but do not meet traditional criteria for COPD, and 3) utilize advanced technology to assess the lung (lung CT) and brain (MRI). We will recruit participants with existing lung CT from ongoing NIH projects to complete pulmonary and vascular measures, cognitive assessment, and brain MRI. The project is highly multidisciplinary and leverages unique resources at the University of Iowa including the CTSA supported Institute for Clinical and Translational Science, the Translational Human Vascular Physiology Lab, the Iowa Neuroimaging Consortium, and the Iowa Comprehensive Lung Imaging Center.

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Study Type : Observational
Estimated Enrollment : 275 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Determinants of Altered Brain Structure and Function in Smokers With COPD-Related Lung Pathophysiology
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : August 31, 2021

Group/Cohort Intervention/treatment
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
Behavioral: Neuropsychological Assessment
Assessments include: Paper and pencil computerized measures of Memory, Language, Visuospatial Function, Executive Functioning-Processing Speed, and Attention

Procedure: Spirometry
Pre and post bronchodilator spirometry will be administered according to ATS guidelines.

Procedure: Arterial Blood Gas
Radial artery blood sample will be collected to measure gas exchange hemoglobin; arterial oxygen and carbon dioxide will be examined as potential covariates.

Procedure: Diffusion Capacity of the Lung for Carbon Monoxide
For measurement of gas exchange in the lung. DLCO adjusted for hemoglobin will be the primary variable of interest and will be examined as a potential covariate.
Other Name: (DLCO)

Diagnostic Test: 6 Minute Walk Test
Distance walked in 6 minutes will be the primary outcome.
Other Name: 6MWT

Procedure: Systemic Vascular Measures
Carotid artery ultrasound, pulse wave velocity, brachial artery endothelium-dependent flow mediated dilation and endothelium-independent dilation will be measured.

Biological: Blood Biomarkers
High sensitivity C-reactive protein (hs-CRP), and fibrinogen will be used as indicators of systemic inflammation, complete blood count with differential (CBC with diff) will be obtained to rule out acute infection as a cause of inflammation.

Behavioral: Symptom Questionnaire Measures
M.I.N.I Screen 7.0.0, Beck Depression Inventory-II (DBI-II), State Trait Anxiety Inventory (STAI), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), MMRC Dyspnea Scale (MMRC), Berlin Questionnaire

Procedure: Brain MRI
Primary neuroimaging outcomes of interest are white matter structural integrity

Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
Behavioral: Neuropsychological Assessment
Assessments include: Paper and pencil computerized measures of Memory, Language, Visuospatial Function, Executive Functioning-Processing Speed, and Attention

Procedure: Spirometry
Pre and post bronchodilator spirometry will be administered according to ATS guidelines.

Procedure: Arterial Blood Gas
Radial artery blood sample will be collected to measure gas exchange hemoglobin; arterial oxygen and carbon dioxide will be examined as potential covariates.

Procedure: Diffusion Capacity of the Lung for Carbon Monoxide
For measurement of gas exchange in the lung. DLCO adjusted for hemoglobin will be the primary variable of interest and will be examined as a potential covariate.
Other Name: (DLCO)

Diagnostic Test: 6 Minute Walk Test
Distance walked in 6 minutes will be the primary outcome.
Other Name: 6MWT

Procedure: Systemic Vascular Measures
Carotid artery ultrasound, pulse wave velocity, brachial artery endothelium-dependent flow mediated dilation and endothelium-independent dilation will be measured.

Biological: Blood Biomarkers
High sensitivity C-reactive protein (hs-CRP), and fibrinogen will be used as indicators of systemic inflammation, complete blood count with differential (CBC with diff) will be obtained to rule out acute infection as a cause of inflammation.

Behavioral: Symptom Questionnaire Measures
M.I.N.I Screen 7.0.0, Beck Depression Inventory-II (DBI-II), State Trait Anxiety Inventory (STAI), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), MMRC Dyspnea Scale (MMRC), Berlin Questionnaire

Procedure: Brain MRI
Primary neuroimaging outcomes of interest are white matter structural integrity

Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
Behavioral: Neuropsychological Assessment
Assessments include: Paper and pencil computerized measures of Memory, Language, Visuospatial Function, Executive Functioning-Processing Speed, and Attention

Procedure: Spirometry
Pre and post bronchodilator spirometry will be administered according to ATS guidelines.

Procedure: Arterial Blood Gas
Radial artery blood sample will be collected to measure gas exchange hemoglobin; arterial oxygen and carbon dioxide will be examined as potential covariates.

Procedure: Diffusion Capacity of the Lung for Carbon Monoxide
For measurement of gas exchange in the lung. DLCO adjusted for hemoglobin will be the primary variable of interest and will be examined as a potential covariate.
Other Name: (DLCO)

Diagnostic Test: 6 Minute Walk Test
Distance walked in 6 minutes will be the primary outcome.
Other Name: 6MWT

Procedure: Systemic Vascular Measures
Carotid artery ultrasound, pulse wave velocity, brachial artery endothelium-dependent flow mediated dilation and endothelium-independent dilation will be measured.

Biological: Blood Biomarkers
High sensitivity C-reactive protein (hs-CRP), and fibrinogen will be used as indicators of systemic inflammation, complete blood count with differential (CBC with diff) will be obtained to rule out acute infection as a cause of inflammation.

Behavioral: Symptom Questionnaire Measures
M.I.N.I Screen 7.0.0, Beck Depression Inventory-II (DBI-II), State Trait Anxiety Inventory (STAI), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), MMRC Dyspnea Scale (MMRC), Berlin Questionnaire

Procedure: Brain MRI
Primary neuroimaging outcomes of interest are white matter structural integrity




Primary Outcome Measures :
  1. White matter (WM) structural integrity from brain magnetic resonance imaging (MRI) [ Time Frame: At the end of data collection in 2021 ]
    Fractional anisotropy from diffusion weighted imaging will be the primary WM measure

  2. Neuropsychological test performance: average executive functioning-processing speed domain summary score [ Time Frame: At the end of data collection in 2021 ]
    The domain summary score represents the average of the norm referenced standardized scores for the following measures: Trail Making Test Part B, Controlled Oral Word Association, Stroop Color Word Test Interference Score, and WAIS-IV Coding


Biospecimen Retention:   Samples With DNA
Stored blood samples may be used to evaluate additional biomarkers. These future studies may provide additional information that will be helpful in understanding COPD and its comorbidities. If consent is given, samples may also be used for potential genetic research.


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Ages Eligible for Study:   30 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants will be recruited from the Iowa COPD research registry, which includes participants from several NIH funded studies with quantitative lung imaging obtained in the Iowa Comprehensive Lung Imaging Center.
Criteria

Inclusion Criteria:

Age 30-85, > 8th grade education, Normal/corrected hearing and vision, English Speaker, Ability to comfortably lie flat for 1 hour.

Exclusion Criteria:

Other concomitant respiratory disorder other than asthma (e.g., cystic fibrosis), Use of antibiotics or steroids for a COPD exacerbation within the past month, Use of 24-hour oxygen, Pregnancy or suspected pregnancy, Uncontrolled cancer within the last 5 years, Radiation therapy to the chest, Lung surgery (LVRS, transplant, lobectomy), Lung cancer known or suspected, Eye surgery in the last 3 months, Pulmonary Hypertension, Insulin-dependent diabetes, Inability to use albuterol, Chest or abdominal surgery in the past 3 months, Heart attack in the last 3 months, Hospitalization for any heart problem in the past month, Prior neurological condition (e.g., stroke, epilepsy, head injury with >15 mins. loss of consciousness), Previous diagnosis of dementia or learning disability, Major comorbid medical conditions with known cognitive effects (e.g., renal failure, HF), Psychotic disorder, bipolar disorder, current substance use disorder other than tobacco use, Change in psychiatric medication in last month, Claustrophobia, Metal object in body that may interfere with neuroimaging.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269721


Contacts
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Contact: Hannatu I Amaza, BS 319-384-9210 hannatu-amaza@uiowa.edu
Contact: Carinda J Linkenmeyer, MA 319-353-8520 Carinda-linkenmeyer@uiowa.edu

Locations
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United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Hannatu I Amaza, B.S.    319-384-9210    hannatu-amaza@uiowa.edu   
Contact: Carinda J Linkenmeyer, M.A.    319-353-8520    carinda-linkenmeyer@uiowa.edu   
Principal Investigator: Karin F Hoth, PhD         
Sub-Investigator: Gary L Pierce, PhD         
Sub-Investigator: Alejandro Comella, MD         
Sub-Investigator: John D Newell, MD         
Sub-Investigator: Peggy Nopoulos, MD         
Sub-Investigator: Vincent A Magnotta, PhD         
Sub-Investigator: Stephan Arndt, PhD         
Sub-Investigator: Eric Hoffman, PhD         
Sponsors and Collaborators
Karin Hoth
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Karin F Hoth, PhD University of Iowa Department of Psychiatry

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Responsible Party: Karin Hoth, Associate Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT03269721     History of Changes
Other Study ID Numbers: 201404738
1R01HL134822-01 ( U.S. NIH Grant/Contract )
First Posted: September 1, 2017    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karin Hoth, University of Iowa:
Cognition
Pulmonary
COPD
Lung
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Lung Diseases, Obstructive
Cognitive Dysfunction
Carbon Monoxide
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Gasotransmitters
Neurotransmitter Agents
Physiological Effects of Drugs