- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03177798
Mitochondria and Chronic Kidney Disease (MitoCKD)
Mitochondrial Dysfunction in Chronic Kidney Disease
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Icatibant then Placebo
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) |
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.
Other Names:
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.
Other Names:
|
EXPERIMENTAL: Placebo then Icatibant
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) |
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
Time Frame: Up to 2 hours after completion of drug infusion
|
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.
|
Up to 2 hours after completion of drug infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Systolic Blood Pressure
Time Frame: 30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis
|
Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis.
|
30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Urologic Diseases
- Renal Insufficiency
- Kidney Diseases
- Renal Insufficiency, Chronic
- Mitochondrial Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Complement Inactivating Agents
- Bradykinin B2 Receptor Antagonists
- Bradykinin Receptor Antagonists
- Icatibant
Other Study ID Numbers
- 131602 (Rutgers Cancer Institute of New Jersey)
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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