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

Phase 4

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Equivalent placebo for 1 year.
Curcumin	Curcumin	25/mg/kg per day for 1 year.

Primary Outcome Measures

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

Secondary Outcome Measures

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