Palm Tocotrienols in Chronic Hemodialysis (Malaysia) (PATCH) (PATCH)

Effects of Dietary Supplementation Using Palm Tocotrienols in Chronic Hemodialysis (PATCH) Patients - A Multicenter Study Evaluating Markers of Inflammation, Oxidative Stress and Blood Lipids

Universiti Putra Malaysia, Malaysia Palm Oil Board, PEMANDU, National Kidney Foundation, Ministry of Health, Malaysia

This study aims to determine if tocotrienol rich fraction (TRF) supplementation can improve markers of inflammation, oxidative stress and blood lipids in Malaysian hemodialysis (HD) patients.

This study is a multi-centered, randomized, double blind, placebo-controlled trial where a total of 400 HD patients (200 supplemented; 200 control) will be recruited from government and private settings. Subjects will be randomized to either the intervention or control group. The intervention group will receive TRF (300 mg), daily for 12 months while the control group will only receive placebo, daily for 12 months. In addition, both groups will receive standard dietary counseling to ensure compliance to medical nutrition therapy guidelines for dialysis patients. Patients who consented will be first subjected to a screening for identification of eligible subjects. The screening will involve basic anthropometry measures (height, weight, BMI), routine biochemistry result obtained from medical record, assessment of nutritional status and dietary evaluation. About 15ml of pre-dialysis blood will be collected by respective nurses for additional laboratory parameters (hsCRP, atherogenic profile and other inflammatory markers). Patients who fulfill the inclusion criteria will be randomized to either control or intervention group. During the 12 months of treatment period, patients in both control and intervention groups will be assessed at baseline and 3-monthly intervals for laboratory results, medical condition, hospitalizations, nutritional status, dietary intake and compliance towards supplementation (intervention group only). A final measurement will be taken 3 months after study completion as a post follow up assessment upon cessation of supplementation. In all, patient data will be generated at 6 time points. (A similar study, following a similar protocol and using the same study design and intervention will recruit 400 patients total (200 for each group) in Michigan, USA).

Based on biochemistry results for TC, LDL-C, HDL-C, triglyceride (TG), atherogenic profile, cholesteryl ester transfer protein (CETP), lecithin cholesterol acyltransferase (LCAT), apolipoprotein A1(ApoA1), apolipoprotein B-100 (ApoB-100)

This includes body mass index (kg/m2) and skin fold measurements such as mid arm circumference (cm), mid-arm muscle circumference (cm), mid-arm muscle area (cm2) and triceps skin fold (mm)

Body composition assessment pertaining to hydration status, lean tissue mass and fat mass is derived using a portable BIA device.

Routine blood parameters (renal, liver function,lipid, hematology profile and dialysis adequacy) will be obtained from patients' medical records. Additional fasted blood sampling will be obtained to determine lipid biomarkers (CETP, LCAT, ApoA1, ApoB-100, lipoprotein particles) as well as inflammation and oxidative stress markers (hs-CRP, IL-6, F-isoprostane).

Dietary intake will be assessed using a 3-day 24-hr diet recalls to determine macro and micronutrient intake.

Patients will be screened with the Malnutrition Inflammation Score questionnaire to categorize their nutritional status.

Difference in frequency of hospitalisation between the groups during the 12 months will be determined.

Metabolomic analyses (using blood specimens) will be carried out to determine differences in metabolites between the groups.

Inclusion Criteria: Provided consent and comply to study protocol Undergoing HD treatment thrice-weekly for > 3 months Adequately dialyzed (Kt/V> 1.2 or urea reduction ratio (URR) of 65%) and hsCRP level <20 mg/dL. Exclusion Criteria: Participated in another clinical trial involving an investigational product in the past 12 weeks preceding enrolment. Planned for kidney transplant over the study duration. Intake of vitamin E-containing supplements (>60 IU/day) 30 days preceding enrolment. Intake of anti-inflammatory medication except aspirin <325 mg/day in the past 30 days preceding enrollment. Female patients who are pregnant, lactating or planning a pregnancy during the course of the trial. Poor adherence to HD or medical treatment Patient with temporary catheter for dialysis access at baseline, or patients receiving graft/fistula within the 6-month study period. History of hospitalizations (>2 times within the past 90 days or one hospitalization within the 30 days) preceding enrollment. Receiving nutritional support ( via enteral and intra-venous route). Diagnosed with HIV/AIDS and/or on the anti-HIV therapy Receiving active treatment for cancer (excluding basal cell carcinoma of the skin). Patients with Hepatitis B or C. Any other significant disease or disorder where in the opinion of the respective nephrologist may affect the end results of this study Patients with a known allergy towards fish.

Daud ZA, Tubie B, Sheyman M, Osia R, Adams J, Tubie S, Khosla P. Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients. Vasc Health Risk Manag. 2013;9:747-61. doi: 10.2147/VHRM.S51710. Epub 2013 Nov 28.

Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000 Oct 7;356(9237):1213-8. doi: 10.1016/s0140-6736(00)02783-5.

Locatelli F, Fouque D, Heimburger O, Drueke TB, Cannata-Andia JB, Horl WH, Ritz E. Nutritional status in dialysis patients: a European consensus. Nephrol Dial Transplant. 2002 Apr;17(4):563-72. doi: 10.1093/ndt/17.4.563.

Sagheb MM, Dormanesh B, Fallahzadeh MK, Akbari H, Sohrabi Nazari S, Heydari ST, Behzadi S. Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial. Sleep Med. 2012 May;13(5):542-5. doi: 10.1016/j.sleep.2011.11.010. Epub 2012 Feb 7.