- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04170855
Kidney Sodium Content in Cardiorenal Patients
Evaluation of Kidney Medullary Sodium Content Using 23Na MRI to Understand and Predict Diuretic Resistance
Diuretic therapy is the cornerstone of the management of fluid overload in heart failure. Resistance to diuretic therapy is the most common reason for treatment failure in patients affected by the combination of heart failure and kidney disease. Currently, there is no way of predicting whether heart failure patients will develop resistance to diuretic therapy and what dose of diuretic is necessary to overcome diuretic resistance. Answering these questions would allow doctors to be able to prescribe an accurate dose of diuretic therapy to prevent diuretic resistance and potential side effects of an excessive diuretic dose.
With magnetic resonance imaging, it is possible to measure the kidney sodium (salt) content and observe the diuretic response in patients with heart failure and kidney disease. The investigators speculate that measuring kidney sodium content will allow to predict diuretic response in these patients.
The aim of this study is to compare the kidney sodium content in patients with chronic cardiorenal syndrome with and without diuretic resistance. Secondly, in a sample of patients with diagnosed diuretic resistance,the aim will be to observe the changes in kidney sodium content induced by an additional dose of diuretic therapy and to observe whether these changes are associated with a response to diuretic therapy.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a prospective, interventional, pilot study involving patients recruited from the Heart Failure outpatient clinic at St. Joseph's Hospital in London, Ontario. Depending on scanner availability, the study visits may also take place at Robarts Research Institute, University of Western Ontario. All eligible patients who consent to take part in the study will undergo one study visit. During this visit, all study participants will undergo a combined proton (1H) and 23Na MRI scan of their kidneys to measure kidney sodium content. Prior to the scan, all participants will be asked to complete a questionnaire, will have their fluid volume measured using bioimpedance spectroscopy, will have their heart failure classified using the NYHA system, will have their weight taken using a clinical scale, and will have their sitting blood pressure and heart rate measured three times consecutively using a standard automatic blood pressure monitor. In addition to this, all participants will undergo a research focused echocardiogram, provide a spot urine sample and have blood work collected. All participants will be responsible to complete a 24-hour urine volume test the day before the study visit and bring the special container to the team on the visit day.
Study participants who meet the criteria for diuretic resistance will undergo a second study visit within one week of the first one. During this visit, participants will receive an additional intravenous dose of diuretic (furosemide) and they will subsequently undergo a second proton and 23Na MRI scan of their kidneys. Prior to the scan participants will undergo the same study procedures as in visit one excluding the questionnaire. In addition to this, participants will be responsible to record their weight at home the morning before the visit and bring their weight to the study team. After the scan, all participants will have their blood pressure, heart, rate, and weight measured again, and will be asked to complete a 24-hour urine collection. Furthermore, participants will be asked to take their weight using a home scale the morning after the scan and a member of the research team will phone the participants to collect this information.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Christopher W McIntyre, MD
- Phone Number: 58502 519.685.8500
- Email: cmcint48@uwo.ca
Study Contact Backup
- Name: Fabio Salerno, MD
- Email: fsalerno@uwo.ca
Study Locations
-
-
Ontario
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London, Ontario, Canada, N6A 3N3
- Recruiting
- Heart Failure Clinic | St. Joseph's Health Care London
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Contact:
- Justin Dorie, RPN
- Phone Number: 56370 519-685-8500
- Email: Justin.Dorie@lhsc.on.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria for Visit 1
- Clinico-pathological diagnosis of heart failure
- Age ≥ 18 years
- Estimated GFR ≥ 15 mL/min/1.73m2
- Receiving loop diuretics for at least a week at ≥ 40 mg/day (furosemide) or 2 mg/day (bumetanide), either orally or intravenously
- Willing and able to provide consent
Inclusion Criteria for Visit 2 · Patients from visit 1 with diuretic resistance
Exclusion Criteria for Visit 1 Direct contraindications to MR scanning (implanted materials etc.)
- Additional diuretic types other than spironolactone/epleronone/metolazone/finerenone
- Liver disease with hepato-renal syndrome
- Pregnant, breastfeeding or intending pregnancy
- Kidney malformation leading to chronic kidney disease (for example polycystic kidney)
- Unable to provide consent
Exclusion criteria for Visit 2
· Hypokalemia (serum potassium <3.5 mmol/l)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Furosemide Injection
Patients with diuretic resistance: The presence of diuretic resistance, defined as having clinical signs of fluid overload despite diuretic therapy (this information is routinely collected at each clinical visit). "Fluid overload" is defined as the presence of at least two of the following clinical features:
|
We will measure kidney sodium content in patient with cardiorenal syndrome. we will inject within the week of this first measurement furosemide only in patient who will be resistant to diuretics (Based on these parameters, diuretic response will be defined as:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Medullary sodium concentration
Time Frame: Through MRI, an average of 60 minutes
|
To demonstrate a statistically significant difference in medullary sodium concentration of at least 100 mmol/L between patients with chronic cardiorenal syndrome who are responsive versus patients who are resistant to their current diuretic therapy.
|
Through MRI, an average of 60 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Corticomedullary sodium gradient
Time Frame: Through MRI, an average of 60 minutes
|
To demonstrate a difference in corticomedullary sodium gradient between patients with chronic cardiorenal syndrome who are responsive versus patients who are resistant to their current diuretic therapy.
|
Through MRI, an average of 60 minutes
|
Change in medullary sodium concentration
Time Frame: Through MRI, an average of 60 minutes
|
To demonstrate a change in medullary sodium concentration compared to baseline in patients with chronic cardiorenal syndrome and diuretic resistance who show a clinical response to an additional diuretic dose, assessed by the lost of weight.
|
Through MRI, an average of 60 minutes
|
Change in corticomedullary sodium gradient
Time Frame: Through MRI, an average of 60 minutes
|
To demonstrate a change in corticomedullary sodium gradient compared to baseline in patients with chronic cardiorenal syndrome and diuretic resistance who show a clinical response to an additional diuretic dose
|
Through MRI, an average of 60 minutes
|
Correlation between kidney sodium content and renal function
Time Frame: Through one study visit, and average of 3 hours
|
To investigate the correlation between kidney sodium content and renal function assessed by GFR measurement (mL/min/1.73m2)
|
Through one study visit, and average of 3 hours
|
Correlation between kidney sodium content and biological cardiac biomarker
Time Frame: Through one study visit, and average of 3 hours
|
To investigate the correlation between kidney sodium content and cardiac biomarkers assessed by NT-ProBNP
|
Through one study visit, and average of 3 hours
|
Correlation between kidney sodium content and inflammation
Time Frame: Through one study visit, and average of 3 hours
|
To investigate the correlation between kidney sodium content and inflammation biomarkers assessed by CRP (mg/dL)
|
Through one study visit, and average of 3 hours
|
Correlation between kidney sodium content and NYHA
Time Frame: Through one study visit, an average of 3 hours
|
To investigate the correlation between kidney sodium content and NYHA class (no unit, scale from 0 to 4)
|
Through one study visit, an average of 3 hours
|
Correlation between kidney sodium content and echocardiography
Time Frame: Through one study visit, an average of 3 hours
|
To investigate the correlation between kidney sodium content and left ejection fraction (in %)
|
Through one study visit, an average of 3 hours
|
Correlation between kidney sodium content and Bioimpedance spectroscopy
Time Frame: Through one study visit, an average of 3 hours
|
To investigate the correlation between kidney sodium content and extra cellular volume content (in liters) measured by bioimpedance spectroscopy.
|
Through one study visit, an average of 3 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Christopher W McIntyre, MD, Western University
Publications and helpful links
General Publications
- Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007 Sep;93(9):1137-46. doi: 10.1136/hrt.2003.025270.
- Chioncel O, Mebazaa A, Harjola VP, Coats AJ, Piepoli MF, Crespo-Leiro MG, Laroche C, Seferovic PM, Anker SD, Ferrari R, Ruschitzka F, Lopez-Fernandez S, Miani D, Filippatos G, Maggioni AP; ESC Heart Failure Long-Term Registry Investigators. Clinical phenotypes and outcome of patients hospitalized for acute heart failure: the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2017 Oct;19(10):1242-1254. doi: 10.1002/ejhf.890. Epub 2017 Apr 30.
- McCullough PA, Kellum JA, Haase M, Muller C, Damman K, Murray PT, Cruz D, House AA, Schmidt-Ott KM, Vescovo G, Bagshaw SM, Hoste EA, Briguori C, Braam B, Chawla LS, Costanzo MR, Tumlin JA, Herzog CA, Mehta RL, Rabb H, Shaw AD, Singbartl K, Ronco C. Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013;182:82-98. doi: 10.1159/000349966. Epub 2013 May 13.
- Clark AL, Kalra PR, Petrie MC, Mark PB, Tomlinson LA, Tomson CR. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-910. doi: 10.1136/heartjnl-2018-314158.
- Jamison RL. The renal concentrating mechanism: micropuncture studies of the renal medulla. Fed Proc. 1983 May 15;42(8):2392-7.
- Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD003838. doi: 10.1002/14651858.CD003838.pub3.
- Maril N, Rosen Y, Reynolds GH, Ivanishev A, Ngo L, Lenkinski RE. Sodium MRI of the human kidney at 3 Tesla. Magn Reson Med. 2006 Dec;56(6):1229-34. doi: 10.1002/mrm.21031.
- Maril N, Margalit R, Mispelter J, Degani H. Sodium magnetic resonance imaging of diuresis: spatial and kinetic response. Magn Reson Med. 2005 Mar;53(3):545-52. doi: 10.1002/mrm.20359.
- Akbari A, Lemoine S, Salerno F, Marcus TL, Duffy T, Scholl TJ, Filler G, House AA, McIntyre CW. Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys. Radiology. 2022 May;303(2):384-389. doi: 10.1148/radiol.211238. Epub 2022 Feb 8.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Heart Failure
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Cardio-Renal Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Sodium Potassium Chloride Symporter Inhibitors
- Furosemide
Other Study ID Numbers
- 114884
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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