Curcumin and Vascular and Cognitive Function in Patients With Chronic Kidney Disease
Condition: Chronic Kidney Diseases; Cognitive Decline
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Curcumin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Oral supplement for 12 months; Oral placebo for 12 months
Other intervention name(s): Longvida
Intervention MeSH terms: Curcumin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Double-Blind Placebo-Controlled Clinical Trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment