Mitochondria and Chronic Kidney Disease (MitoCKD)
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| ClinicalTrials.gov Identifier: NCT03177798 |
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Recruitment Status :
Completed
First Posted : June 6, 2017
Results First Posted : October 29, 2019
Last Update Posted : October 29, 2019
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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 |
| 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 |
|---|---|
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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 |
- 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.
- 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.
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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 |
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
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
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37232 | |
Documents provided by Jorge Gamboa, Vanderbilt University Medical Center:
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Kidney Diseases Renal Insufficiency, Chronic Mitochondrial Diseases Urologic Diseases Renal Insufficiency Metabolic Diseases Icatibant 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 |