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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Curcumin | Experimental | 25/mg/kg per day for 1 year. |
|
| Placebo | Placebo Comparator | Equivalent placebo for 1 year. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Curcumin | Drug | Dietary Supplement |
|
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Alanine Transaminase (ALT ) | Liver enzymes will be monitored for safety. | month 1, 6, and 12 |
| Change in Aspartate Aminotransferase (AST) | Liver enzymes will be monitored for safety. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristen L Nowak, Ph.D. | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anschutz Medical Campus | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34907021 | Derived | Nowak KL, Farmer-Bailey H, Wang W, You Z, Steele C, Cadnapaphornchai MA, Klawitter J, Patel N, George D, Jovanovich A, Soranno DE, Gitomer B, Chonchol M. Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2022 Feb;17(2):240-250. doi: 10.2215/CJN.08950621. Epub 2021 Dec 14. |
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Data obtained through this study may be provided to qualified researchers with academic interest in ADPKD. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. data use agreement) are prerequisites to the sharing of data with the requesting party.
Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
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| ID | Title | Description |
|---|---|---|
| FG000 | Curcumin | 25/mg/kg per day for 1 year. Curcumin: Dietary Supplement |
| FG001 | Placebo | Equivalent placebo for 1 year. Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Curcumin | 25/mg/kg per day for 1 year. Curcumin: Dietary Supplement |
| BG001 | Placebo | Equivalent placebo for 1 year. Placebo |
| 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 | Percent Change in Brachial Artery Flow-mediated Dilation (FMD-BA) | co-primary endpoint | Posted | Mean | 95% Confidence Interval | percent change | Baseline, Month 12 |
|
|
12 Months
Rows listed to include multiple adverse events (i.e., "Flatulence, constipation, diarrhea, or nausea") were monitored/assessed in this manner.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Curcumin | 25/mg/kg per day for 1 year. Curcumin: Dietary Supplement | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal issues | Gastrointestinal disorders | Systematic Assessment | Flatulence, constipation, diarrhea, or nausea |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kristen Nowak, Ph.D. | University of Colorado Denver | Anschutz | 303-724-1111 | clinicalresearchsupportcenter@ucdenver.edu |
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| 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 | Mar 12, 2020 | Dec 1, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 11, 2020 | Dec 1, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| ID | Term |
|---|---|
| D007690 | Polycystic Kidney Diseases |
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D003474 | Curcumin |
| ID | Term |
|---|---|
| D036381 | Diarylheptanoids |
| D006536 | Heptanes |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
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| Placebo |
| Other |
|
| 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 |
| month 1, 6, and 12 |
| Change in Height-corrected Total Kidney Volume | Total kidney volume will be measured by MRI | Baseline, Month 12 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Estimated Glomerular Filtration Rate | Measure of kidney function. A score of about 100 would mean that kidneys are functioning properly. Lower scores mean lower function, and a worse outcome. | Mean | Standard Deviation | ml/minute/1.73m^2 |
|
|
|
| Primary | Change in Aortic Pulse-wave Velocity (aPWV) (cm/Sec) | co-primary endpoint | Posted | Mean | 95% Confidence Interval | cm/sec | Baseline, Month 12 |
|
|
|
| Secondary | Change in Urinary 8-iso-prostaglandin F2α (8-isoprostane) | Urine marker of oxidative stress. Values are normalized to urinary creatinine. | Some participants were excluded because 12 month data was not collected. | Posted | Mean | 95% Confidence Interval | mg/dl | Baseline, Month 12 |
|
|
|
| Secondary | Change in C-reactive Protein | Circulating marker of inflammation | Some participants were excluded because their 12 month data was not collected. | Posted | Mean | 95% Confidence Interval | mg/L | Baseline, Month 12 |
|
|
|
| Secondary | Change in Interleukin-6 | Circulating marker of inflammation | Some participants were excluded because 12 month data was not collected. | Posted | Mean | 95% Confidence Interval | picograms/mL | Baseline, Month 12 |
|
|
|
| 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. | This outcome measure was only collected for a subgroup of participants | Posted | Mean | Standard Deviation | Percent change | Baseline, Month 12 |
|
|
|
| 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. | This outcome measure was not collected for any participants. | Posted | Baseline, Month 12 |
|
|
| Other Pre-specified | Change in Alanine Transaminase (ALT ) | Liver enzymes will be monitored for safety. | Not Posted | month 1, 6, and 12 | Participants |
| Other Pre-specified | Change in Aspartate Aminotransferase (AST) | Liver enzymes will be monitored for safety. | Not Posted | month 1, 6, and 12 | Participants |
| Other Pre-specified | Change in Height-corrected Total Kidney Volume | Total kidney volume will be measured by MRI | Not Posted | Baseline, Month 12 | Participants |
| 34 |
| 0 |
| 34 |
| 15 |
| 34 |
| EG001 | Placebo | Equivalent placebo for 1 year. Placebo | 0 | 34 | 0 | 34 | 9 | 34 |
|
| Warming or redness of face | Vascular disorders | Systematic Assessment |
|
| Tingling of tongue/mouth | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Dry Mouth | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Eye redness, dryness, or swelling | Eye disorders | Systematic Assessment |
|
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |