Mitochondria and Chronic Kidney Disease

Mitochondrial Diseases Clinical Trial

— MitoCKD  

Official title:

Mitochondrial Dysfunction in Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03177798
• Other study ID #: 131602
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: October 2019
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 31, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 78 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemodialysis-Induced Symptom
• Kidney Diseases
• Mitochondrial Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Icatibant
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2 hours after completion of drug infusion
Secondary	Systolic Blood Pressure	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