Clinical trial NCT03773991: Dyspnea Assessment in Hemodialysis Patients
Official title: Multimodal Assessment of Dyspnea, Cardiopulmonary Structure and Function in Chronic Hemodialysis Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Dyspnea; Uremic
End Stage Renal Disease
Chronic Lung Disease
Chronic Heart Disease
Hemodialysis-Induced Symptom
Sodium Excess
Keywords: Dyspnea
Hemodialysis
End Stage Renal Disease
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2018-12-12
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients for this trial will be recruited from incident and prevalent hemodialysis patients receiving care for their kidney disease from the Dialysis Service at London Health Sciences Centre, London Ontario. Up to 20 eligible patients will be recruited.

Brief summary: Shortness of breath is very common among patients on dialysis for kidney failure; however, its causes are often not understood. This study will explore the lungs and the heart of these patients to determine the causes of shortness of breath. The amount of salt in the body tissues, which tends to accumulate in dialysis patients and can also cause shortness of breath, will also be measured. Machines that exploit magnetic resonance, ultrasound and x-rays to take images of the body interior will be employed; in addition, breathing tests, questionnaires and blood tests will also be used. 20 patients on dialysis will be recruited and have two visits: one at the beginning of the study and one year later to observe any changes in the lungs, heart and salt accumulation over time.

Detailed description: Rationale:

The available evidence suggest that End-Stage Renal Disease (ESRD) and hemodialysis (HD) have harmful effects on the lungs; the investigators hypothesize that these recurring pulmonary insults, in an analogous way as recurring myocardial ischemic injury for the heart, cause long term impairment in the pulmonary parenchyma, airways and circulation. In addition, observational studies have reported that dyspnea is a common symptom among ESRD patients on chronic HD treatment; however, no study up to now has directly addressed the issue, so that the relationship between dyspnea and pulmonary involvement in the HD population remains poorly understood.

The aim of this study is to explore the pathophysiological basis of dyspnea in patients with end stage renal disease on chronic HD, by using state-of-the-art imaging and functional study techniques.

Study Design:

This is an exploratory study involving a single center recruiting patients from the prevalent dialysis population of London, Ontario. 20 patients on maintenance hemodialysis will be recruited. The patients will undergo imaging, functional studies and blood sampling at the Robarts Research Institute on a non-dialysis day, during the short interval in the dialysis schedule, at baseline and after one year.

Study Procedures:

Blood Collection: blood will be collected from a venous access for standard-of-care tests, uremia and inflammation biomarkers.

Dyspnea Assessment: dyspnea will be assessed with the following self-administered questionnaires: Modified Medical Research Council Breathlessness Scale, the University of California, San Diego Shortness of Breath Questionnaire Pulmonary Function Tests: spirometry and plethysmography pre and post salbutamol administration, carbon monoxide diffusion (DLCO) and the fractional exhaled nitric oxide (FeNO) will be evaluated.

Six Minute Walk Test: the subjects able to do so will perform a six minute walk test, their dyspnea and overall fatigue at baseline and at the end of the exercise will be evaluated using the Borg Scale.

Lung MRI: a proton MRI with ultrashort echo time (UTE) acquisition sequences for the study of lung parenchyma and lung water will be employed. Images will be acquired twice, both pre and post a bronchodilator (salbutamol) challenge.

Sodium MRI: a proton T1 weighted fast-low-angle-shot (FLASH)- sequence will be acquired to delineate the anatomy of the lower leg. Then, a sodium MRI study of the subjects' legs (\~5 cm below the knee) will be obtained with the custom-made sodium coil at 3.0 Tesla.

Water content will also be quantified using proton-MRI with fat-suppressed inversion recovery sequence with proton density contrast.

Chest CT: a high-resolution chest CT scan will be performed using a 64-slice CT scanner. A low radiation dose protocol will be employed. A qualitative and quantitative evaluation of pulmonary airways, blood vessels and parenchyma will be performed.

2D Transthoracic Echocardiography: images will be taken in the left lateral decubitus. Images and loops from standard parasternal long axis and short axis, subcostal, apical 4, 2 and 3- chamber views will be recorded and analyzed for: global longitudinal strain, left ventricular ejection fraction, left ventricular mass, left atrial volume, right ventricular diameter, right atrial volume, right ventricular wall thickness, tricuspid annular plane systolic excursion, pulmonary artery systolic pressure, E/A ratio, E/E' ratio at the basal interventricular septum, aortic, mitral, tricuspid and pulmonary valve qualitative and quantitative function.

Eligibility criteria: Inclusion Criteria:

* Age equal to or greater than 18 years.
* Dialysis vintage equal to or greater than 3 months.

Exclusion Criteria

* Smoking history of more than 10 packs/year.
* Active tobacco and/or cannabis smoking.
* Diagnosed chronic pulmonary disease.
* Severe heart failure (NYHA class IV)
* Active infection (including tuberculosis) or malignancy.
* Pregnancy.
* Inability to give consent or understand written information.
* Peripheral oxygen saturation (by pulse oxymetry) dropping below 80% when performing a 12-seconds breathhold.
* Inability to perform spirometry or plethysmography maneuvers.
* Inability to tolerate MRI due to patient size and/or known history of claustrophobia.
* Subject has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants.).

Primary outcomes:
measure: Baseline Modified Medical Research Council scale score.
timeFrame: Baseline
measure: Baseline University of California, San Diego Shortness of Breath Questionnaire score.
timeFrame: Baseline
measure: Baseline pulmonary artery diameter.
timeFrame: Baseline
measure: Baseline lung total blood vessel volume.
timeFrame: Baseline
measure: Baseline lung total airway count.
timeFrame: Baseline
measure: Baseline lung low attenuation area.
timeFrame: Baseline
measure: Baseline lung water content.
timeFrame: Baseline
measure: Baseline soft tissue sodium content.
timeFrame: Baseline
Secondary outcomes:
measure: One year changes in Modified Medical Research Council scale score.
timeFrame: Baseline and one year
measure: Correlation between baseline modified Medical Research Council scale score and one year morbidity.
timeFrame: Baseline and one year
measure: Correlation between baseline modified Medical Research Council scale score and one year mortality.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and soft tissue sodium content.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and pulmonary artery diameter.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and lung total blood vessel volume.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and lung total airway count.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and lung low attenuation areas.
timeFrame: Baseline and one year
measure: Correlation between modified Medical Research Council scale score and lung total water content.
timeFrame: Baseline and one year
measure: One year changes in University of California, San Diego Shortness of Breath Questionnaire score.
timeFrame: Baseline and one year
measure: Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year morbidity.
timeFrame: Baseline and one year
measure: Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year mortality.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and soft tissue sodium content.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas.
timeFrame: Baseline and one year
measure: Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content.
timeFrame: Baseline and one year
measure: One year changes in lung total blood vessel volume.
timeFrame: Baseline and one year
measure: One year changes in lung total airway count.
timeFrame: Baseline and one year
measure: One year changes in lung water content.
timeFrame: Baseline and one year
measure: One year changes in lung low attenuation areas.
timeFrame: Baseline and one year
measure: One year changes in pulmonary artery diameter.
timeFrame: Baseline and one year
measure: Baseline pulmonary artery systolic pressure.
timeFrame: Baseline
measure: One year changes in pulmonary artery systolic pressure.
timeFrame: Baseline and one year
measure: Baseline fractional exhaled nitric oxide.
timeFrame: Baseline
measure: One year changes in fractional exhaled nitric oxide.
timeFrame: Baseline and one year
measure: Baseline forced expiratory volume at one second/forced vital capacity ratio.
timeFrame: Baseline
measure: One year changes in forced expiratory volume at one second/forced vital capacity ratio.
timeFrame: Baseline and one year
measure: Baseline diffusing capacity of the lung for carbon monoxide.
timeFrame: Baseline
measure: One year changes in diffusing capacity of the lung for carbon monoxide.
timeFrame: Baseline and one year
measure: Baseline six minute walk distance.
timeFrame: Baseline
measure: One year changes in six minute walk distance.
timeFrame: Baseline and one year
measure: One year changes in soft tissue sodium content.
timeFrame: Baseline and one year
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Christopher W McIntyre, MD PhD
role: PRINCIPAL_INVESTIGATOR
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