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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02494141
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 2
• Actual Duration (Months): 62.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Kidney, Autosomal Dominant	Drug: Curcumin; Other: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults With ADPKD
• Actual Study Start Date: Nov 12, 2015
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Curcumin 25/mg/kg per day for 1 year.	Drug: Curcumin; Dietary Supplement; Other Names: Longvida
Placebo Comparator: Placebo Equivalent placebo for 1 year.	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) [Baseline, Month 12]

   co-primary endpoint

2. Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) [Baseline, Month 12]

   co-primary endpoint

Secondary Outcome Measures

1. Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) [Baseline, Month 12]

   Urine marker of oxidative stress. Values are normalized to urinary creatinine.

2. Change in C-reactive Protein [Baseline, Month 12]

   Circulating marker of inflammation

3. Change in Interleukin-6 [Baseline, Month 12]

   Circulating marker of inflammation

4. 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.

5. 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 Outcome Measures

1. Change in Alanine Transaminase (ALT ) [month 1, 6, and 12]

   Liver enzymes will be monitored for safety.

2. Change in Aspartate Aminotransferase (AST) [month 1, 6, and 12]

   Liver enzymes will be monitored for safety.

3. Change in Height-corrected Total Kidney Volume [Baseline, Month 12]

   Total kidney volume will be measured by MRI

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Kristen L Nowak, Ph.D., University of Colorado - Anschutz Medical Campus

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 12, 2020
• Informed Consent Form - Dec 11, 2020

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02494141
• Other Study ID Numbers: 15-0902
• First Posted: Jul 10, 2015
• Last Update Posted: Mar 3, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Curcumin

Study Results

Participant Flow

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Period Title: Overall Study
STARTED	34	34
COMPLETED	28	29
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Curcumin	Placebo	Total
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo	Total of all reporting groups
Overall Participants	34	34	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18 (6)	19 (5)	18 (5)
Sex: Female, Male (Count of Participants)
Female	19 55.9%	18 52.9%	37 54.4%
Male	15 44.1%	16 47.1%	31 45.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.9%	4 11.8%	6 8.8%
Not Hispanic or Latino	32 94.1%	30 88.2%	62 91.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.9%	0 0%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	33 97.1%	32 94.1%	65 95.6%
More than one race	0 0%	2 5.9%	2 2.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%	34 100%	68 100%
Estimated Glomerular Filtration Rate (ml/minute/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/minute/1.73m^2]	115 (16)	118 (19)	117 (17)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA)
Description	co-primary endpoint
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	34	34
Mean (95% Confidence Interval) [percent change]	1.14	0.3

2. Primary Outcome

Title	Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec)
Description	co-primary endpoint
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	34	34
Mean (95% Confidence Interval) [cm/sec]	0.6	6.5

3. Secondary Outcome

Title	Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane)
Description	Urine marker of oxidative stress. Values are normalized to urinary creatinine.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Some participants were excluded because 12 month data was not collected.

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	28	29
Mean (95% Confidence Interval) [mg/dl]	0.00	0.27

4. Secondary Outcome

Title	Change in C-reactive Protein
Description	Circulating marker of inflammation
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Some participants were excluded because their 12 month data was not collected.

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	27	29
Mean (95% Confidence Interval) [mg/L]	0.21	0.17

5. Secondary Outcome

Title	Change in Interleukin-6
Description	Circulating marker of inflammation
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Some participants were excluded because 12 month data was not collected.

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	27	29
Mean (95% Confidence Interval) [picograms/mL]	2.24	2.33

6. Secondary Outcome

Title	Percent Change in Oxidative Stress-associated Suppression of Endothelium-dependent Dilation (EDD)
Description	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

Outcome Measure Data

Analysis Population Description

This outcome measure was only collected for a subgroup of participants

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	12	12
Baseline	3.0 (0.95)	1.7 (3.0)
Month 12	1.1 (3.5)	1.4 (2.6)

7. Secondary Outcome

Title	Change in Oxidative Stress-Associated Suppression of Large Elastic Artery Stiffness
Description	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

Outcome Measure Data

Analysis Population Description

This outcome measure was not collected for any participants.

Arm/Group Title	Curcumin	Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement	Equivalent placebo for 1 year. Placebo
Measure Participants	0	0

8. Other Pre-specified Outcome

Title	Change in Alanine Transaminase (ALT )
Description	Liver enzymes will be monitored for safety.
Time Frame	month 1, 6, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Change in Aspartate Aminotransferase (AST)
Description	Liver enzymes will be monitored for safety.
Time Frame	month 1, 6, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Change in Height-corrected Total Kidney Volume
Description	Total kidney volume will be measured by MRI
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	12 Months
Adverse Event Reporting Description	Rows listed to include multiple adverse events (i.e., "Flatulence, constipation, diarrhea, or nausea") were monitored/assessed in this manner.
Arm/Group Title	Curcumin		Placebo
Arm/Group Description	25/mg/kg per day for 1 year. Curcumin: Dietary Supplement		Equivalent placebo for 1 year. Placebo
All Cause Mortality
	Curcumin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/34 (0%)
Serious Adverse Events
	Curcumin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Curcumin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/34 (44.1%)		9/34 (26.5%)
Eye disorders
Eye redness, dryness, or swelling	2/34 (5.9%)	2	0/34 (0%)	0
Gastrointestinal disorders
Gastrointestinal issues	7/34 (20.6%)	7	7/34 (20.6%)	7
General disorders
Headache	1/34 (2.9%)	1	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Tingling of tongue/mouth	2/34 (5.9%)	2	0/34 (0%)	0
Skin and subcutaneous tissue disorders
Dry Mouth	0/34 (0%)	0	1/34 (2.9%)	1
Skin irritation	1/34 (2.9%)	1	0/34 (0%)	0
Vascular disorders
Warming or redness of face	2/34 (5.9%)	2	0/34 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.