Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults With ADPKD

Study Overview
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Brief Summary
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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
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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.

Official Title
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Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults With ADPKD

Conditions
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Polycystic Kidney, Autosomal Dominant

Intervention / Treatment
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* Drug: Curcumin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curcumin<br>25/mg/kg per day for 1 year. | Drug: Curcumin<br>* Dietary Supplement<br>* Other names: Longvida;|
| Placebo Comparator: Placebo<br>Equivalent placebo for 1 year. | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) | co-primary endpoint | Baseline, Month 12 | 
| Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) | co-primary endpoint | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) | Urine marker of oxidative stress. Values are normalized to urinary creatinine. | Baseline, Month 12 | 
| Change in C-reactive Protein | Circulating marker of inflammation | Baseline, Month 12 | 
| Change in Interleukin-6 | Circulating marker of inflammation | Baseline, Month 12 | 
| 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. | Baseline, Month 12 | 
| 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. | Baseline, Month 12 |