Dyspnea; UremicNCT03773991
Dyspnea Assessment in Hemodialysis Patients
An observational study of Dyspnea; Uremic and End Stage Renal Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dyspnea; Uremic, End Stage Renal Disease, Chronic Lung Disease
- What is being tested?
- Lung MRI, Sodium MRI and Chest CT
- How many people
- 7 participants
- Where
- 1 siteCanada
- Study dates
- 29 Mar 2019to 25 Feb 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Age equal to or greater than 18 years.
- Dialysis vintage equal to or greater than 3 months.
Who cannot join
- 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.
Show all 11Show fewer
- 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.).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multimodal Assessment of Dyspnea, Cardiopulmonary Structure and Function in Chronic Hemodialysis Patients
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.
Read the 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.
- Conditions
- Dyspnea; Uremic, End Stage Renal Disease, Chronic Lung Disease, Chronic Heart Disease, Hemodialysis-Induced Symptom, Sodium Excess
- Being tested
- Lung MRI, Sodium MRI, Chest CT, Echocardiography, Fractional Exhaled Nitric Oxide
- Keywords
- Dyspnea, Hemodialysis, End Stage Renal Disease
- Medical subject headings
- Dyspnea, Kidney Failure, Chronic, Hypernatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung MRIDiagnostic test
Proton Lung Magnetic Resonance Imaging
Sodium MRIDiagnostic test
Sodium Soft Tissue Magnetic Resonance Imaging
Chest CTDiagnostic test
High-resolution Quantitative Chest CT
EchocardiographyDiagnostic test
Transthoracic 2D Speckle-Tracking Echocardiography
Fractional Exhaled Nitric OxideDiagnostic test
Fractional Exhaled Nitric Oxide testing
Pulmonary Function TestsDiagnostic test
Spirometry and Plethysmography
Blood SamplingDiagnostic test
Blood testing for: standard-of-care, inflammatory biomarkers, uremic toxins
Six-Minute Walk TestDiagnostic test
Six-Minute Walk Test
Dyspnea QuestionnairesDiagnostic test
Modified Medical Research Council; University of California, San Diego Shortness of Breath Questionnaire; Borg Scale
| Study group | Role | What they receive |
|---|---|---|
| Maintenance Hemodialysis Patients | Patients on chronic hemodialysis therapy due to end-stage renal disease.
* Proton Lung MRI
* Sodium MRI of the leg
* Chest CT
* Transthoracic Echocardiography
* Fractional Exhaled Nitric Oxide
* Six-Minute Walk Test
* Pulmonary Function Tests
* Blood sampling
* Self-administered dyspnea questionnaires Receives: Diagnostic Test: Lung MRI; Diagnostic Test: Sodium MRI; Diagnostic Test: Chest CT; Diagnostic Test: Echocardiography; Diagnostic Test: Fractional Exhaled Nitric Oxide; Diagnostic Test: Pulmonary Function Tests; Diagnostic Test: Blood Sampling; Diagnostic Test: Six-Minute Walk Test; Diagnostic Test: Dyspnea Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Modified Medical Research Council scale score.
Baseline dyspnea measured by Modified Medical Research Council scale. 0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Measured: Baseline
Baseline University of California, San Diego Shortness of Breath Questionnaire score.
Baseline dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire.
0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Measured: Baseline
Baseline pulmonary artery diameter.
Baseline pulmonary artery diameter (in millimeters) by chest Computed Tomography.
Measured: Baseline
Baseline lung total blood vessel volume.
Baseline lung total blood vessel volume in ml by chest Computed Tomography.
Measured: Baseline
Baseline lung total airway count.
Baseline lung total airway count by chest Computed Tomography.
Measured: Baseline
Baseline lung low attenuation area.
Baseline lung low attenuation area by chest Computed Tomography.
Measured: Baseline
Baseline lung water content.
Baseline lung water content in arbitrary units measured by proton Magnetic Resonance Imaging.
Measured: Baseline
Baseline soft tissue sodium content.
Baseline soft tissue sodium content in mmol/L measured by sodium Magnetic Resonance Imaging.
Measured: Baseline
Secondary outcomes (34)
One year changes in Modified Medical Research Council scale score.
Comparison of dyspnea measured by Modified Medical Research Council scale at one year versus baseline.
0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Measured: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year morbidity.
One year morbidity risk by modified Medical Research Council scale baseline score.
Measured: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year mortality.
One year mortality risk by modified Medical Research Council scale baseline score.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and soft tissue sodium content.
Correlation coefficient between soft tissue sodium content (mmol/L) and modified Medical Research Council scale score.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and pulmonary artery diameter.
Correlation coefficient between modified Medical Research Council scale score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total blood vessel volume.
Correlation coefficient between modified Medical Research Council scale score and lung total blood vessel volume (in milliliters), measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total airway count.
Correlation coefficient between modified Medical Research Council scale score and lung total airway count, measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and lung low attenuation areas.
Correlation coefficient between modified Medical Research Council scale score and lung low attenuation areas, measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total water content.
Correlation coefficient between modified Medical Research Council scale score and lung total water content (in arbitrary units), measured by proton Magnetic Resonance Imaging.
Measured: Baseline and one year
One year changes in University of California, San Diego Shortness of Breath Questionnaire score.
Comparison of dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire at one year versus baseline.
0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Measured: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year morbidity.
One year morbidity risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Measured: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year mortality.
One year mortality risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and soft tissue sodium content.
Correlation coefficient between soft tissue sodium content (mmol/L) and University of California, San Diego Shortness of Breath Questionnaire score.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume (in milliliters), measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count, measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas, measured by chest Computed Tomography.
Measured: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content (in arbitrary units), measured by proton Magnetic Resonance Imaging.
Measured: Baseline and one year
One year changes in lung total blood vessel volume.
Comparison of lung total blood vessel volume (in milliliters) at one year versus baseline, measured by chest Computed Tomography.
Measured: Baseline and one year
One year changes in lung total airway count.
Comparison of lung total airway count at one year versus baseline, measured by chest Computed Tomography.
Measured: Baseline and one year
One year changes in lung water content.
Comparison of lung water content (in arbitrary units) at one year versus baseline, measured by proton Magnetic Resonance Imaging.
Measured: Baseline and one year
One year changes in lung low attenuation areas.
Comparison of lung low attenuation areas at one year versus baseline, measured by chest Computed Tomography.
Measured: Baseline and one year
One year changes in pulmonary artery diameter.
Comparison of pulmonary artery diameter (in millimeters) at one year versus baseline, measured by chest Computed Tomography.
Measured: Baseline and one year
Baseline pulmonary artery systolic pressure.
Baseline pulmonary artery systolic pressure (in mmHg), measured by transthoracic doppler echocardiography.
Measured: Baseline
One year changes in pulmonary artery systolic pressure.
Comparison of pulmonary artery systolic pressure in mmHg at one year versus baseline, measured by transthoracic doppler echocardiography.
Measured: Baseline and one year
Baseline fractional exhaled nitric oxide.
Baseline fractional exhaled nitric oxide measured (in parts per billion).
Measured: Baseline
One year changes in fractional exhaled nitric oxide.
Comparison of fractional exhaled nitric oxide measured (in parts per billion) at one year versus baseline.
Measured: Baseline and one year
Baseline forced expiratory volume at one second/forced vital capacity ratio.
Baseline forced expiratory volume at one second/forced vital capacity ratio by pulmonary function tests.
Measured: Baseline
One year changes in forced expiratory volume at one second/forced vital capacity ratio.
Comparison of forced expiratory volume at one second/forced vital capacity ratio at one year versus baseline, by pulmonary function tests.
Measured: Baseline and one year
Baseline diffusing capacity of the lung for carbon monoxide.
Baseline diffusing capacity of the lung for carbon monoxide (in ml/min/kPa), by pulmonary function tests.
Measured: Baseline
One year changes in diffusing capacity of the lung for carbon monoxide.
Comparison of diffusing capacity of the lung for carbon monoxide (in ml/min/kPa) at one year versus baseline, by pulmonary function tests
Measured: Baseline and one year
Baseline six minute walk distance.
Baseline six minute walk distance (in meters) measured by six minute walk test.
Measured: Baseline
One year changes in six minute walk distance.
Comparison of six minute walk distance (in meters) at one year versus baseline, measured by six minute walk test.
Measured: Baseline and one year
One year changes in soft tissue sodium content.
Comparison of soft tissue sodium content (in mmol/L) at one year versus baseline, measured by sodium Magnetic Resonance Imaging.
Measured: Baseline and one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start29 Mar 2019
- Primary completion25 Feb 2020
- Study completion25 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Dyspnea; UremicStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chris McIntyre, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Christopher W McIntyre, MD PhD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03773991
- Sponsor's protocol ID
- 110256
- Status last verified
- Aug 2024
- First submitted
- 29 Nov 2018
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murtagh FE, Addington-Hall JM, Edmonds PM, Donohoe P, Carey I, Jenkins K, Higginson IJ. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J Palliat Med. 2007 Dec;10(6):1266-76. doi: 10.1089/jpm.2007.0017.
PubMed 18095805Fairshter RD, Vaziri ND, Mirahmadi MK. Lung pathology in chronic hemodialysis patients. Int J Artif Organs. 1982 Mar;5(2):97-100.
PubMed 7095887Zoccali C, Torino C, Tripepi R, Tripepi G, D'Arrigo G, Postorino M, Gargani L, Sicari R, Picano E, Mallamaci F; Lung US in CKD Working Group. Pulmonary congestion predicts cardiac events and mortality in ESRD. J Am Soc Nephrol. 2013 Mar;24(4):639-46. doi: 10.1681/ASN.2012100990. Epub 2013 Feb 28.
PubMed 23449536Nascimento MM, Qureshi AR, Stenvinkel P, Pecoits-Filho R, Heimburger O, Cederholm T, Lindholm B, Barany P. Malnutrition and inflammation are associated with impaired pulmonary function in patients with chronic kidney disease. Nephrol Dial Transplant. 2004 Jul;19(7):1823-8. doi: 10.1093/ndt/gfh190. Epub 2004 May 18.
PubMed 15150347Wallin CJ, Jacobson SH, Leksell LG. Subclinical pulmonary oedema and intermittent haemodialysis. Nephrol Dial Transplant. 1996 Nov;11(11):2269-75. doi: 10.1093/oxfordjournals.ndt.a027147.
PubMed 8941589Bolignano D, Rastelli S, Agarwal R, Fliser D, Massy Z, Ortiz A, Wiecek A, Martinez-Castelao A, Covic A, Goldsmith D, Suleymanlar G, Lindholm B, Parati G, Sicari R, Gargani L, Mallamaci F, London G, Zoccali C. Pulmonary hypertension in CKD. Am J Kidney Dis. 2013 Apr;61(4):612-22. doi: 10.1053/j.ajkd.2012.07.029. Epub 2012 Nov 17.
PubMed 23164943Barak M, Nakhoul F, Katz Y. Pathophysiology and clinical implications of microbubbles during hemodialysis. Semin Dial. 2008 May-Jun;21(3):232-8. doi: 10.1111/j.1525-139X.2008.00424.x. Epub 2008 Mar 18.
PubMed 18363602Plesner LL, Warming PE, Nielsen TL, Dalsgaard M, Schou M, Host U, Rydahl C, Brandi L, Kober L, Vestbo J, Iversen K. Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis. Hemodial Int. 2016 Jan;20(1):68-77. doi: 10.1111/hdi.12342. Epub 2015 Aug 5.
PubMed 26245152Pabst S, Hammerstingl C, Hundt F, Gerhardt T, Grohe C, Nickenig G, Woitas R, Skowasch D. Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One. 2012;7(4):e35310. doi: 10.1371/journal.pone.0035310. Epub 2012 Apr 18.
PubMed 22530005Herrero JA, Alvarez-Sala JL, Coronel F, Moratilla C, Gamez C, Sanchez-Alarcos JM, Barrientos A. Pulmonary diffusing capacity in chronic dialysis patients. Respir Med. 2002 Jul;96(7):487-92. doi: 10.1053/rmed.2002.1346.
PubMed 12194631Kovacevic P, Stanetic M, Rajkovaca Z, Meyer FJ, Vukoja M. Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy. Pneumologia. 2011 Jan-Mar;60(1):36-9.
PubMed 21545062McIntyre CW, Odudu A. Hemodialysis-associated cardiomyopathy: a newly defined disease entity. Semin Dial. 2014 Mar;27(2):87-97. doi: 10.1111/sdi.12197.
PubMed 24738144Belem LC, Zanetti G, Souza AS Jr, Hochhegger B, Guimaraes MD, Nobre LF, Rodrigues RS, Marchiori E. Metastatic pulmonary calcification: state-of-the-art review focused on imaging findings. Respir Med. 2014 May;108(5):668-76. doi: 10.1016/j.rmed.2014.01.012. Epub 2014 Feb 6.
PubMed 24529738Incalzi RA, Corsonello A, Pedone C, Battaglia S, Paglino G, Bellia V; Extrapulmonary Consequences of COPD in the Elderly Study Investigators. Chronic renal failure: a neglected comorbidity of COPD. Chest. 2010 Apr;137(4):831-7. doi: 10.1378/chest.09-1710. Epub 2009 Nov 10.
PubMed 19903974Romoff MS, Keusch G, Campese VM, Wang MS, Friedler RM, Weidmann P, Massry SG. Effect of sodium intake on plasma catecholamines in normal subjects. J Clin Endocrinol Metab. 1979 Jan;48(1):26-31. doi: 10.1210/jcem-48-1-26. No abstract available.
PubMed 422701
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Assessment of Dyspnea, Cardiopulmonary Structure and Function in Chronic Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT03773991
- Acronym / sponsor ID
- 110256
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 29 Mar 2019 (actual)
- Primary completion
- 25 Feb 2020 (actual)
- Study completion
- 25 Feb 2020 (actual)
- First posted
- 12 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Maintenance Hemodialysis Patients | – | Diagnostic Test: Lung MRI, Diagnostic Test: Sodium MRI, Diagnostic Test: Chest CT, Diagnostic Test: Echocardiography, Diagnostic Test: Fractional Exhaled Nitric Oxide, Diagnostic Test: Pulmonary Function Tests, Diagnostic Test: Blood Sampling, Diagnostic Test: Six-Minute Walk Test, Diagnostic Test: Dyspnea QuestionnairesPatients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Age equal to or greater than 18 years.
- Dialysis vintage equal to or greater than 3 months.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lung MRIProton Lung Magnetic Resonance Imaging | Diagnostic test | Maintenance Hemodialysis Patients |
| Sodium MRISodium Soft Tissue Magnetic Resonance Imaging | Diagnostic test | Maintenance Hemodialysis Patients |
| Chest CTHigh-resolution Quantitative Chest CT | Diagnostic test | Maintenance Hemodialysis Patients |
| EchocardiographyTransthoracic 2D Speckle-Tracking Echocardiography | Diagnostic test | Maintenance Hemodialysis Patients |
| Fractional Exhaled Nitric OxideFractional Exhaled Nitric Oxide testing | Diagnostic test | Maintenance Hemodialysis Patients |
| Pulmonary Function TestsSpirometry and Plethysmography | Diagnostic test | Maintenance Hemodialysis Patients |
| Blood SamplingBlood testing for: standard-of-care, inflammatory biomarkers, uremic toxins | Diagnostic test | Maintenance Hemodialysis Patients |
| Six-Minute Walk TestSix-Minute Walk Test | Diagnostic test | Maintenance Hemodialysis Patients |
| Dyspnea QuestionnairesModified Medical Research Council; University of California, San Diego Shortness of Breath Questionnaire; Borg Scale | Diagnostic test | Maintenance Hemodialysis Patients |
Primary outcome
Baseline Modified Medical Research Council scale score.
Time frame: Baseline
Baseline dyspnea measured by Modified Medical Research Council scale. 0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Baseline University of California, San Diego Shortness of Breath Questionnaire score.
Time frame: Baseline
Baseline dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire. 0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Baseline pulmonary artery diameter.
Time frame: Baseline
Baseline pulmonary artery diameter (in millimeters) by chest Computed Tomography.
Baseline lung total blood vessel volume.
Time frame: Baseline
Baseline lung total blood vessel volume in ml by chest Computed Tomography.
Baseline lung total airway count.
Time frame: Baseline
Baseline lung total airway count by chest Computed Tomography.
Baseline lung low attenuation area.
Time frame: Baseline
Baseline lung low attenuation area by chest Computed Tomography.
Baseline lung water content.
Time frame: Baseline
Baseline lung water content in arbitrary units measured by proton Magnetic Resonance Imaging.
Baseline soft tissue sodium content.
Time frame: Baseline
Baseline soft tissue sodium content in mmol/L measured by sodium Magnetic Resonance Imaging.
34 secondary outcomes
One year changes in Modified Medical Research Council scale score.
Time frame: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year morbidity.
Time frame: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year mortality.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and soft tissue sodium content.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and pulmonary artery diameter.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total blood vessel volume.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total airway count.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung low attenuation areas.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total water content.
Time frame: Baseline and one year
One year changes in University of California, San Diego Shortness of Breath Questionnaire score.
Time frame: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year morbidity.
Time frame: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year mortality.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and soft tissue sodium content.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content.
Time frame: Baseline and one year
One year changes in lung total blood vessel volume.
Time frame: Baseline and one year
One year changes in lung total airway count.
Time frame: Baseline and one year
One year changes in lung water content.
Time frame: Baseline and one year
One year changes in lung low attenuation areas.
Time frame: Baseline and one year
One year changes in pulmonary artery diameter.
Time frame: Baseline and one year
Baseline pulmonary artery systolic pressure.
Time frame: Baseline
One year changes in pulmonary artery systolic pressure.
Time frame: Baseline and one year
Baseline fractional exhaled nitric oxide.
Time frame: Baseline
One year changes in fractional exhaled nitric oxide.
Time frame: Baseline and one year
Baseline forced expiratory volume at one second/forced vital capacity ratio.
Time frame: Baseline
One year changes in forced expiratory volume at one second/forced vital capacity ratio.
Time frame: Baseline and one year
Baseline diffusing capacity of the lung for carbon monoxide.
Time frame: Baseline
One year changes in diffusing capacity of the lung for carbon monoxide.
Time frame: Baseline and one year
Baseline six minute walk distance.
Time frame: Baseline
One year changes in six minute walk distance.
Time frame: Baseline and one year
One year changes in soft tissue sodium content.
Time frame: Baseline and one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Background: PubMed 18095805Murtagh FE, Addington-Hall JM, Edmonds PM, Donohoe P, Carey I, Jenkins K, Higginson IJ. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J Palliat Med. 2007 Dec;10(6):1266-76. doi: 10.1089/jpm.2007.0017.
- Background: PubMed 7095887Fairshter RD, Vaziri ND, Mirahmadi MK. Lung pathology in chronic hemodialysis patients. Int J Artif Organs. 1982 Mar;5(2):97-100.
- Background: PubMed 23449536Zoccali C, Torino C, Tripepi R, Tripepi G, D'Arrigo G, Postorino M, Gargani L, Sicari R, Picano E, Mallamaci F; Lung US in CKD Working Group. Pulmonary congestion predicts cardiac events and mortality in ESRD. J Am Soc Nephrol. 2013 Mar;24(4):639-46. doi: 10.1681/ASN.2012100990. Epub 2013 Feb 28.
- Background: PubMed 15150347Nascimento MM, Qureshi AR, Stenvinkel P, Pecoits-Filho R, Heimburger O, Cederholm T, Lindholm B, Barany P. Malnutrition and inflammation are associated with impaired pulmonary function in patients with chronic kidney disease. Nephrol Dial Transplant. 2004 Jul;19(7):1823-8. doi: 10.1093/ndt/gfh190. Epub 2004 May 18.
- Background: PubMed 8941589Wallin CJ, Jacobson SH, Leksell LG. Subclinical pulmonary oedema and intermittent haemodialysis. Nephrol Dial Transplant. 1996 Nov;11(11):2269-75. doi: 10.1093/oxfordjournals.ndt.a027147.
- Background: PubMed 23164943Bolignano D, Rastelli S, Agarwal R, Fliser D, Massy Z, Ortiz A, Wiecek A, Martinez-Castelao A, Covic A, Goldsmith D, Suleymanlar G, Lindholm B, Parati G, Sicari R, Gargani L, Mallamaci F, London G, Zoccali C. Pulmonary hypertension in CKD. Am J Kidney Dis. 2013 Apr;61(4):612-22. doi: 10.1053/j.ajkd.2012.07.029. Epub 2012 Nov 17.
- Background: PubMed 18363602Barak M, Nakhoul F, Katz Y. Pathophysiology and clinical implications of microbubbles during hemodialysis. Semin Dial. 2008 May-Jun;21(3):232-8. doi: 10.1111/j.1525-139X.2008.00424.x. Epub 2008 Mar 18.
- Background: PubMed 26245152Plesner LL, Warming PE, Nielsen TL, Dalsgaard M, Schou M, Host U, Rydahl C, Brandi L, Kober L, Vestbo J, Iversen K. Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis. Hemodial Int. 2016 Jan;20(1):68-77. doi: 10.1111/hdi.12342. Epub 2015 Aug 5.
- Background: PubMed 22530005Pabst S, Hammerstingl C, Hundt F, Gerhardt T, Grohe C, Nickenig G, Woitas R, Skowasch D. Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One. 2012;7(4):e35310. doi: 10.1371/journal.pone.0035310. Epub 2012 Apr 18.
- Background: PubMed 12194631Herrero JA, Alvarez-Sala JL, Coronel F, Moratilla C, Gamez C, Sanchez-Alarcos JM, Barrientos A. Pulmonary diffusing capacity in chronic dialysis patients. Respir Med. 2002 Jul;96(7):487-92. doi: 10.1053/rmed.2002.1346.
- Background: PubMed 21545062Kovacevic P, Stanetic M, Rajkovaca Z, Meyer FJ, Vukoja M. Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy. Pneumologia. 2011 Jan-Mar;60(1):36-9.
- Background: PubMed 24738144McIntyre CW, Odudu A. Hemodialysis-associated cardiomyopathy: a newly defined disease entity. Semin Dial. 2014 Mar;27(2):87-97. doi: 10.1111/sdi.12197.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher W McIntyre, MD PhD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dyspnea; Uremic and End Stage Renal Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline Modified Medical Research Council scale score. (time frame: Baseline). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03773991, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024.