Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Cross-over design, eleven individuals receive both treatments, Icatibant and placbo
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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). Washout, then 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) Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. |
| FG001 | 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). Washout, then 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). Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients on hemodialysis three times a week for at least six months
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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) Washout, then 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) Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | seconds | Up to 2 hours after completion of drug infusion |
|
6 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Icatibant | 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). Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for cardiac catheterization | Cardiac disorders | Systematic Assessment | Unrelated to the study intervention. Patient require cardiac stent placement due to coronary artery disease |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Patient was admitted for possible kidney transplant | Renal and urinary disorders | Systematic Assessment | Patient did not match and was not eligible for kidney transplant |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jorge L. Gamboa | Vanderbilt University Medical Center | 615-343-4176 | jorge.gamboa@vumc.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 9, 2017 | Aug 20, 2019 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D028361 | Mitochondrial Diseases |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C065679 | icatibant |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| 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. |
|
|
| BG001 | 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). Washout, then 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). Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 30 minutes prior to the initiation of dialysis and continue through hemodialysis (4 hours) 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. |
|
|
| Secondary | Systolic Blood Pressure | Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis. | Posted | Mean | Standard Deviation | mmHg | 30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 1 |
| 11 |
| EG001 | Placebo | 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). Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy. | 0 | 11 | 2 | 11 | 1 | 11 |
|
| Hypovolemia | Gastrointestinal disorders | Systematic Assessment | Unrelated to the study. Patients was hospitalized due to hypovolemia secondary to gastrointestinal disorders |
|
|
| Arterious venous access thrombosis | Blood and lymphatic system disorders | Non-systematic Assessment | Unrelated to the the study. Patient had thrombosis of the AV access that requires revascularization. |
|
Not provided
Not provided
| up to 1 hour after hemodialysis |
|