Back to resultsMitochondria and Chronic Kidney Disease (MitoCKD)
Primary Purpose
Hemodialysis-Induced Symptom, Mitochondrial Diseases
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Icatibant
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Hemodialysis-Induced Symptom
Eligibility Criteria
Inclusion Criteria:
- Adult patients who have been on maintenance hemodialysis for at least 6 months
Exclusion Criteria:
- History of functional transplant less than 6 months prior to study
- Use of immunosuppressive drugs within 1 month prior to study
- History of active connective tissue disease
- History of acute infectious disease within one month prior to study
- AIDS (HIV seropositivity is not an exclusion criteria)
- History of myocardial infarction or cerebrovascular event within 3 months
- Advanced liver disease
- Gastrointestinal dysfunction requiring parental nutrition
- Active malignancy excluding basal cell carcinoma of the skin
- Ejection fraction less than 30%
- Anticipated live donor kidney transplant
- Pregnancy, breast-feeding or child-bearing potential
- History of poor adherence to hemodialysis or medical regimen
- Subjects with cardiac pacemaker, artificial heart valve, any metallic implant, permanent tattoo, or any retained foreign metallic bodies that are contraindicated in magnetic resonance imaging.
- Inability to provide consent
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Icatibant then Placebo
Placebo then Icatibant
Arm Description
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours) 1 week washout Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours) 1 week washout Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
Outcomes
Primary Outcome Measures
Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
Mitochondria function will be evaluated using 31P-MRS, which evaluates the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules. After basal measurements, subjects will be asked to perform 90 seconds of knee extension followed by 4 minutes of rest. The exercise/rest cycle will be repeated 3 times. Magnetic resonance spectra will be used to calculate concentrations of inorganic phosphate (Pi), PCr, and adenosine triphosphate (ATP). The time constant tau of PCr recovery (time to achieve 66.3% maximal concentration during recovery) will be used to determine mitochondrial function.
Secondary Outcome Measures
Systolic Blood Pressure
Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis.
Full Information
NCT ID
NCT03177798
First Posted
May 8, 2017
Last Updated
October 28, 2019
Sponsor
Vanderbilt University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03177798
Brief Title
Mitochondria and Chronic Kidney Disease
Acronym
MitoCKD
Official Title
Mitochondrial Dysfunction in Chronic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The overarching goal of this study is to determine the role of chronic kidney disease and the activation of the kallikrein-kinin system during hemodialysis on the development of mitochondrial dysfunction; the investigators will measure mitochondrial function using the gold standard method, 31-phosphorus magnetic resonance spectroscopy.
The investigators will test the hypothesis that endogenous bradykinin promotes mitochondrial dysfunction in patients undergoing hemodialysis. The investigators will first perform a randomized, placebo-controlled, double-blind, cross-over study measuring the effect of Icatibant (HOE-140), a bradykinin B2 receptor blocker, on mitochondrial function.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemodialysis-Induced Symptom, Mitochondrial Diseases
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Icatibant then Placebo
Arm Type
Experimental
Arm Description
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
Arm Title
Placebo then Icatibant
Arm Type
Experimental
Arm Description
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
Intervention Type
Drug
Intervention Name(s)
Icatibant
Other Intervention Name(s)
HOE-140
Intervention Description
Subjects will receive either Icatibant or placebo in the first study day. After a washout period of 3 weeks, participant will receive the other treatment. Icatibant (50µg/kg/h) or placebo will be infused for 1 hour prior to the initiation of dialysis and continue through hemodialysis. Hemodialysis session will last approximately 4 hours. Two hours after the end of hemodialysis, The investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo infusion
Intervention Description
Subjects will receive either Icatibant or placebo in the first study day. After a washout period of 3 weeks, participant will receive the other treatment. Icatibant (50µg/kg/h) or placebo will be infused for 1 hour prior to the initiation of dialysis and continue through hemodialysis. Hemodialysis session will last approximately 4 hours. Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy.
Primary Outcome Measure Information:
Title
Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
Description
Mitochondria function will be evaluated using 31P-MRS, which evaluates the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules. After basal measurements, subjects will be asked to perform 90 seconds of knee extension followed by 4 minutes of rest. The exercise/rest cycle will be repeated 3 times. Magnetic resonance spectra will be used to calculate concentrations of inorganic phosphate (Pi), PCr, and adenosine triphosphate (ATP). The time constant tau of PCr recovery (time to achieve 66.3% maximal concentration during recovery) will be used to determine mitochondrial function.
Time Frame
Up to 2 hours after completion of drug infusion
Secondary Outcome Measure Information:
Title
Systolic Blood Pressure
Description
Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis.
Time Frame
30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
78 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients who have been on maintenance hemodialysis for at least 6 months
Exclusion Criteria:
History of functional transplant less than 6 months prior to study
Use of immunosuppressive drugs within 1 month prior to study
History of active connective tissue disease
History of acute infectious disease within one month prior to study
AIDS (HIV seropositivity is not an exclusion criteria)
History of myocardial infarction or cerebrovascular event within 3 months
Advanced liver disease
Gastrointestinal dysfunction requiring parental nutrition
Active malignancy excluding basal cell carcinoma of the skin
Ejection fraction less than 30%
Anticipated live donor kidney transplant
Pregnancy, breast-feeding or child-bearing potential
History of poor adherence to hemodialysis or medical regimen
Subjects with cardiac pacemaker, artificial heart valve, any metallic implant, permanent tattoo, or any retained foreign metallic bodies that are contraindicated in magnetic resonance imaging.
Inability to provide consent
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Mitochondria and Chronic Kidney Disease
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