Polycystic Kidney, Autosomal Dominant
Conditions
Brief summary
The proposed research will determine the effectiveness of curcumin for improving the health and function of arteries in children and young adults with autosomal dominant polycystic kidney disease (ADPKD). The study also will provide insight into how curcumin improves artery health by determining the physiological mechanisms (biological reasons) involved and offer exploratory evidence if curcumin can slow kidney growth. This will be done by comparing these measurements in children and young adults who are randomized to receive either curcumin or placebo for 1 year.
Detailed description
Although often considered to be a disease of adults, complications of autosomal dominant polycystic kidney disease (ADPKD) begin in childhood. While ADPKD causes the continued growth of multiple kidney cysts that ultimately result in loss of kidney function, the leading cause of death among patients with ADPKD is cardiovascular disease. Treatment options to prevent cardiovascular disease in adults with ADPKD are limited, thus childhood may be an important time to reduce risk. Curcumin is a safe, naturally occurring substance found in the Indian spice tumeric, which is in curry powder. The proposed research will determine the effectiveness of curcumin for improving the health and function of arteries in children and young adults with ADPKD. The study also will provide insight into how curcumin improves artery health by determining the physiological mechanisms (biological reasons) involved and offer exploratory evidence if curcumin can slow kidney growth. This will be done by comparing these measurements in children and young adults who are randomized to receive either curcumin or placebo for 1 year.
Interventions
DRUGCurcumin
Dietary Supplement
OTHERPlacebo
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* ADPKD diagnosis * Normal renal function (estimated glomerular filtration rate \>80 mL/min/1.73m\^2) * Ability to provide informed consent
Exclusion criteria
* Currently taking a curcumin supplement * Current smoking or history of smoking in the past 12 months * Marijuana use within 2 weeks prior to FMDBA and aPWV testing * Antioxidantand/or omega-3 fatty acid use within the past 4 weeks prior to FMDBA and aPWV testing and for the duration of the study * Alcohol dependence and abuse * History of hospitalization within the last 3 months * Active infection or antibiotic therapy * Pregnancy, lactation, or unwillingness to use adequate birth control * Body-mass index \>95th percentile in ages 6-17 or \>40 kg/m2 in ages 18-25 * Inability to cooperate with/clinical contraindication for MRI including severe claustrophobia, implants, devices, or non-removable body piercings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) | Baseline, Month 12 | co-primary endpoint |
| Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) | Baseline, Month 12 | co-primary endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-reactive Protein | Baseline, Month 12 | Circulating marker of inflammation |
| Change in Interleukin-6 | Baseline, Month 12 | Circulating marker of inflammation |
| Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) | Baseline, Month 12 | Urine marker of oxidative stress. Values are normalized to urinary creatinine. |
| Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD) | Baseline, Month 12 | The influence of oxidative stress on FMD-BA will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline. The outcome measure describes the value of the percent change with ascorbic acid compared to saline observed at baseline and the value of the percent change with ascorbic acid compared to saline at the month 12 timepoint. |
| Change in Oxidative Stress-Associated Suppression of Large Elastic Artery Stiffness | Baseline, Month 12 | The influence of oxidative stress on aPWV will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Aspartate Aminotransferase (AST) | month 1, 6, and 12 | Liver enzymes will be monitored for safety. |
| Change in Alanine Transaminase (ALT ) | month 1, 6, and 12 | Liver enzymes will be monitored for safety. |
| Change in Height-corrected Total Kidney Volume | Baseline, Month 12 | Total kidney volume will be measured by MRI |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Curcumin 25/mg/kg per day for 1 year.
Curcumin: Dietary Supplement | 34 |
| Placebo Equivalent placebo for 1 year.
Placebo | 34 |
| Total | 68 |
Baseline characteristics
| Characteristic | Curcumin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 18 years STANDARD_DEVIATION 6 | 19 years STANDARD_DEVIATION 5 | 18 years STANDARD_DEVIATION 5 |
| Estimated Glomerular Filtration Rate | 115 ml/minute/1.73m^2 STANDARD_DEVIATION 16 | 118 ml/minute/1.73m^2 STANDARD_DEVIATION 19 | 117 ml/minute/1.73m^2 STANDARD_DEVIATION 17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 30 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 32 Participants | 65 Participants |
| Region of Enrollment United States | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Male | 15 Participants | 16 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 15 / 34 | 9 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec)
co-primary endpoint
Time frame: Baseline, Month 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) | 0.6 cm/sec |
| Placebo | Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) | 6.5 cm/sec |
Primary
Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA)
co-primary endpoint
Time frame: Baseline, Month 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) | 1.14 percent change |
| Placebo | Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) | 0.3 percent change |
Secondary
Change in C-reactive Protein
Circulating marker of inflammation
Time frame: Baseline, Month 12
Population: Some participants were excluded because their 12 month data was not collected.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Change in C-reactive Protein | 0.21 mg/L |
| Placebo | Change in C-reactive Protein | 0.17 mg/L |
Secondary
Change in Interleukin-6
Circulating marker of inflammation
Time frame: Baseline, Month 12
Population: Some participants were excluded because 12 month data was not collected.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Change in Interleukin-6 | 2.24 picograms/mL |
| Placebo | Change in Interleukin-6 | 2.33 picograms/mL |
Secondary
Change in Oxidative Stress-Associated Suppression of Large Elastic Artery Stiffness
The influence of oxidative stress on aPWV will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline.
Time frame: Baseline, Month 12
Population: This outcome measure was not collected for any participants.
Secondary
Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane)
Urine marker of oxidative stress. Values are normalized to urinary creatinine.
Time frame: Baseline, Month 12
Population: Some participants were excluded because 12 month data was not collected.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) | 0.00 mg/dl |
| Placebo | Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) | 0.27 mg/dl |
Secondary
Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD)
The influence of oxidative stress on FMD-BA will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline. The outcome measure describes the value of the percent change with ascorbic acid compared to saline observed at baseline and the value of the percent change with ascorbic acid compared to saline at the month 12 timepoint.
Time frame: Baseline, Month 12
Population: This outcome measure was only collected for a subgroup of participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD) | Baseline | 3.0 Percent change | Standard Deviation 0.95 |
| Curcumin | Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD) | Month 12 | 1.1 Percent change | Standard Deviation 3.5 |
| Placebo | Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD) | Baseline | 1.7 Percent change | Standard Deviation 3 |
| Placebo | Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD) | Month 12 | 1.4 Percent change | Standard Deviation 2.6 |
Other Pre-specified
Change in Alanine Transaminase (ALT )
Liver enzymes will be monitored for safety.
Time frame: month 1, 6, and 12
Other Pre-specified
Change in Aspartate Aminotransferase (AST)
Liver enzymes will be monitored for safety.
Time frame: month 1, 6, and 12
Other Pre-specified
Change in Height-corrected Total Kidney Volume
Total kidney volume will be measured by MRI
Time frame: Baseline, Month 12