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Mitochondria and Chronic Kidney Disease (MitoCKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03177798
Recruitment Status : Completed
First Posted : June 6, 2017
Results First Posted : October 29, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Jorge Gamboa, 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.


Condition or disease Intervention/treatment Phase
Hemodialysis-Induced Symptom Mitochondrial Diseases Drug: Icatibant Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Mitochondrial Dysfunction in Chronic Kidney Disease
Actual Study Start Date : August 1, 2017
Actual Primary Completion Date : June 30, 2018
Actual Study Completion Date : December 31, 2018


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)

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.
Other Name: HOE-140

Drug: 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.
Other Name: placebo infusion

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)

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.
Other Name: HOE-140

Drug: 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.
Other Name: placebo infusion




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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%
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03177798


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
  Study Documents (Full-Text)

Documents provided by Jorge Gamboa, Vanderbilt University Medical Center:

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Responsible Party: Jorge Gamboa, Research Associate Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03177798    
Other Study ID Numbers: 131602
First Posted: June 6, 2017    Key Record Dates
Results First Posted: October 29, 2019
Last Update Posted: October 29, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Mitochondrial Diseases
Urologic Diseases
Renal Insufficiency
Metabolic Diseases
Icatibant
Bradykinin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Bradykinin B2 Receptor Antagonists
Bradykinin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Vasodilator Agents