Mitochondria and Chronic Kidney Disease

Phase 2

Completed

Conditions: Hemodialysis-Induced Symptom
Mitochondrial Diseases

Interventions: Drug: Icatibant
Drug: Placebo

Registration Number: NCT03177798

Lead Sponsor: Vanderbilt University Medical Center

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Icatibant then Placebo	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)
Placebo then Icatibant	Placebo	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)
Icatibant then Placebo	Icatibant	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 then Icatibant	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)

Primary Outcome Measures

Name	Time	Method
Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)	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 Outcome Measures

Name	Time	Method
Systolic Blood Pressure	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.