Mitochondria and Chronic Kidney Disease (MitoCKD)

Vanderbilt University Medical Center

Status and phase: Completed; Phase 2

Conditions: Hemodialysis-Induced Symptom; Mitochondrial Diseases

Treatments: Drug: Placebo; Drug: Icatibant

Study type: Interventional

Funder types: Other

Identifiers

NCT03177798

131602

Details and patient eligibility

About

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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 78 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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11 participants in 2 patient groups

Icatibant then Placebo

Experimental group

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)

Treatment:

Drug: Icatibant

Drug: Placebo

Placebo then Icatibant

Experimental group

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)

Treatment:

Drug: Icatibant

Drug: Placebo