Curcumin in Kidney Transplant Recipients

Study Overview
=================
Brief Summary
-----------------
The primary goal of this study is to investigate if curcumin is beneficial for kidney transplant recipients, a population with extensive baseline vascular dysfunction and cognitive impairment who have few treatment options. The possible mechanisms by which curcumin improves vascular function will be evaluated as well as whether curcumin improves cognitive function in these patients.

Detailed Description
-----------------
Kidney transplant recipients 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 kidney transplant recipients and contribute to the high incidence of CVD in this patient population. The most common cause of kidney transplant failure is interstitial fibrosis and tubular atrophy (IFTA). The incidence of IFTA is as high as 50% of kidney transplants at 1 year after transplantation. The pathophysiology of IFTA is not well understood. Possible mechanisms include chronic rejection or injury, inflammation, and drug toxicity. Kidney transplant recipients suffer from high rates of cognitive decline for which the investigators lack effective therapies. Thus, therapeutic interventions targeting inflammation, oxidative stress, vascular dysfunction, and cognitive impairment are a priority. Curcumin may have positive effects in terms of cardiovascular and nephroprotection because of its antibacterial, antiviral, anti-inflammatory and anti-oxidative effects. The aim of this study is to elucidate the role of curcumin as a nutritional strategy to reduce cardiovascular risk factors as well as inflammation and oxidative stress in kidney transplant recipients. The study aims to examine if curcumin will improve endothelial function by reducing markers of inflammation and oxidative stress. In addition, the study will evaluate the potential benefit of curcumin on cognitive function in kidney transplant recipients. Curcumin is a natural polyphenol with anti-inflammatory and antioxidant characteristics. Preliminary data indicate that curcumin administration improves endothelial dysfunction by reducing oxidative stress and inflammation and may improve cognitive function. The primary goal of this study is to investigate if curcumin is beneficial for kidney transplant recipients, a population with extensive baseline vascular dysfunction and cognitive impairment who have few treatment options. The possible mechanisms by which curcumin improves vascular function will be evaluated as well as whether curcumin improves cognitive function in these patients. Objectives: Evaluate the effects of curcumin on kidney transplant graft function Evaluate the effects of curcumin supplementation on cognitive function. Evaluate the effects of curcumin on diabetes and cardiovascular outcomes Evaluate the effects of curcumin on systemic and endothelial cell markers of inflammation and oxidative stress. Methods: Patients will be randomized 1:1 to receive either curcumin or placebo starting at the time of transplant or up to 2 weeks prior to transplant. Patients will be followed per standard of care for kidney transplant recipients. Additional blood (30mL) and urine samples will be drawn prior to transplant and at 3, 6 and 12 months post-transplant to be used for future analysis. There will be a total of 4 visits for this study. Additionally, two questionnaires will be distributed at each visit.

Official Title
-----------------
A Pilot 12 Month, Randomized, Controlled Trial of Curcumin in Kidney Transplant Recipients

Conditions
-----------------
Disorder Related to Renal Transplantation

Intervention / Treatment
-----------------
* Dietary Supplement: Curcumin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is a recipient of a living donor or deceased donor kidney only transplant The subject is > 18 years of age Exclusion Criteria: The subject has had a multi-organ transplant Subjects that were taking curcumin pre-transplant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 20 participants in supplement (receiving curcumin) group 20 participants in control (receiving placebo) group randomization 1:1
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curcumin Arm (Arm 1)<br>20 subjects will be randomized (1:1) to this arm and receive curcumin for a year. In addition, subjects will have four study visits at Day 0, and 3, 6 and 12 months post-transplant. These study visits also include blood samples and questionnaires. | Dietary Supplement: Curcumin<br>* Patients will receive curcumin 2000 mg a day, for 12 months<br>* Other names: Longvida;|
| Placebo Comparator: Placebo Arm (Arm 2)<br>20 subjects will be randomized (1:1) to this arm and receive placebo for a year. In addition, subjects will have four study visits at Day 0, and 3, 6 and 12 months post-transplant. These study visits also include blood samples and questionnaires. | Other: Placebo<br>* Patients will receive placebo capsule identical in appearance and taste to the supplement, for 12 months<br>* Other names: Longvida;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft Outcomes | Change in GFR at 3, 6 and 12 months | 12 months | 
| Cognitive function & Pain | Change in Neuro-QOL Item Bank v2.0 at 0, 3, 6, and 12 months | 12 months | 
| Graft Outcomes | Difference in biopsy scores at 3 and 12 months | 12 months | 
| Cognitive function & Pain | Global Pain Scale at 0, 3, 6, and 12 months | 12 months | 
| Inflammation and oxidative stress | Markers of inflammation and oxidative stress at 0,3,6, & 12 months | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
kidney transplantation, inflammation, vascular dysfunction, cognitive impairment, oxidative stress, graft function