Mitochondrial Dysfunction in Chronic Kidney Disease
Overview
- Phase
- Phase 2
- Intervention
- Icatibant
- Conditions
- Hemodialysis-Induced Symptom
- Sponsor
- Vanderbilt University Medical Center
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Jorge Gamboa
Research Associate Professor
Vanderbilt University Medical Center
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%
Arms & Interventions
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)
Intervention: Icatibant
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)
Intervention: Placebo
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)
Intervention: Icatibant
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)
Intervention: Placebo
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Systolic Blood Pressure(30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis)