Curcumin and Vascular and Cognitive Function in Patients With Chronic Kidney Disease

Curcumin Supplementation for Improving Vascular and Cognitive Function in Chronic Kidney Disease

The proposed research is clinical study evaluating the therapeutic benefits of curcumin on vascular function in patients with chronic kidney disease (CKD). The study aims to establish that curcumin will improve endothelial function and reduce large artery stiffness by reducing oxidative stress and in conjunction with lowering markers of inflammation and oxidative stress. In addition, the study will evaluate the potential benefit of curcumin on cognitive function in patients with CKD.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Cognitive Decline
• Intervention / Treatment: Drug: Curcumin; Other: Placebo

Detailed Description

Patients with chronic kidney disease (CKD) are at increased risk of death from cardiovascular disease (CVD). Inflammation, oxidative stress and vascular dysfunction (impaired endothelial function and increased large elastic artery stiffness), are highly prevalent in CKD and contribute to the high incidence of CVD in this patient population. In addition, patients with CKD suffer from high rates of cognitive decline for which we lack effective therapies. Thus, therapeutic interventions targeting inflammation, oxidative stress, vascular dysfunction, and cognitive impairment in CKD are a biomedical priority.

Curcumin is a natural polyphenol with anti-inflammatory and antioxidant characteristics. It is safe and widely-available. Preliminary data in old mice and healthy middle-aged (MA)/older adult humans indicate that curcumin administration improves endothelial dysfunction and large artery stiffness by reducing oxidative stress and inflammation. Additionally, 12 weeks of curcumin supplementation improves episodic memory in MA/older adults.

The primary goal of this R01 application is to extend previous findings in healthy MA/older adults to patients with CKD, a growing clinical population with extensive baseline vascular dysfunction and cognitive impairment who presently have few treatment options. The hypothesis is that curcumin improves vascular endothelial function and large elastic artery stiffness in MA/older adults with stage IIIb and IV CKD (estimated GFR 15-45 mL/min/1.73m2). The possible mechanisms by which curcumin improves vascular function will be evaluated as well as whether curcumin improves cognitive function in these patients.

Specific aim 1a will determine if 12 months of curcumin supplementation will improve brachial artery-flow mediated dilation (BA-FMD) (endothelial function) and aortic pulse wave velocity (aPWV) (arterial stiffness) compared to placebo (randomized placebo-controlled double-blind study). Specific aim 1b will evaluate whether the curcumin-induced improvements in BA-FMD and aPWV are mediated by reduced oxidative stress, and will evaluate the effects of curcumin on systemic and endothelial cell markers of inflammation and oxidative stress. Importantly, specific aim 2 will evaluate the effects of curcumin supplementation on cognitive function, an important complication of CKD, using the NIH Cognitive Toolbox Battery.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• CKD stage IIIB and IV
• BMI<35 kg/m2
• Able to give informed consent

Exclusion Criteria:

• Consuming a diet rich in curcumin or taking curcumin supplements in the past 12 months
• Life expectancy <1 year
• Pregnant, breastfeeding, or unwilling to use adequate birth control
• Uncontrolled hypertension
• Severe liver disease
• Severe congestive heart failure
• Hospitalization within the last 3 months
• Active infection or antibiotic therapy
• Immunosuppressive therapy within the last year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will receive placebo pill identical in appearance and taste to the supplement	Other: Placebo; Oral placebo for 12 months
Experimental: Curcumin; Patients will receive curcumin (Lonvida) 2000 mg PO once a day	Drug: Curcumin; Oral supplement for 12 months; Other Names: Longvida

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Vascular Endothelial Function at 12 Months	Brachial artery flow-mediated dilation, changed in diameter in brachial artery in response to shear stress	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Large Artery Stiffness	Aortic pulse wave velocity	12 months
Cognitive Function	NIH toolbox battery- Executive Function Age-Corrected Standard Score is reported (T-score): This score compares the score of the test-taker to those in the NIH Toolbox nationally representative normative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. Age-corrected standard scores were derived separately for children (ages 3-17) and adults (ages 18-85). A score of 115 or 85, for example, would indicate that the participant's performance is 1 SD above or below the national average, respectively, when compared with like-aged participants. Higher scores indicate better performance.	12 months

Collaborators and Investigators

• Sponsor: Diana Jalal
• Collaborators: University of Colorado, Denver; Stanford University; University of Colorado, Boulder
• Investigators: Principal Investigator: Diana Jalal, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): January 25, 2023
• Study Completion (Actual): January 25, 2023

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Urologic Diseases; Neurocognitive Disorders; Disease Attributes; Renal Insufficiency; Cognition Disorders; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Cognitive Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Curcumin
• Other Study ID Numbers: 201710769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No