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

Phase 2

Completed

Conditions: Chronic Kidney Diseases
Cognitive Decline

Interventions: Other: Placebo
Drug: Curcumin

Registration Number: NCT03223883

Lead Sponsor: Diana Jalal

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 94

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will receive placebo pill identical in appearance and taste to the supplement
Curcumin	Curcumin	Patients will receive curcumin (Lonvida) 2000 mg PO once a day

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Large Artery Stiffness	12 months	Aortic pulse wave velocity
Cognitive Function	12 months	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.