Mitochondria and Chronic Kidney Disease

NCT03177798 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 131602
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemodialysis-Induced Symptom; Mitochondrial Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Systolic Blood Pressure

  30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis

Study Arms (2)

Icatibant then Placebo

EXPERIMENTAL

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; Drug: Placebo

Placebo then Icatibant

EXPERIMENTAL

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; Drug: Placebo

Interventions

Icatibant DRUG

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.

Also known as: HOE-140

Icatibant then Placebo; Placebo then Icatibant

Placebo DRUG

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.

Also known as: placebo infusion

Icatibant then Placebo; Placebo then Icatibant

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients who have been on maintenance hemodialysis for at least 6 months

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Mitochondrial Diseases

Interventions

icatibant

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Jorge L. Gamboa
• Organization: Vanderbilt University Medical Center

jorge.gamboa@vumc.org

615-343-4176

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: June 6, 2017
• Study Start: August 1, 2017
• Primary Completion: June 30, 2018
• Study Completion: December 31, 2018
• Last Updated: October 29, 2019
• Results First Posted: October 29, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)