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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Failure
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: TRF

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 55000
    • Hospital Kuala Lumpur
  • Cheras
    • Kuala Lumpur, Cheras, Malaysia, 56000
      • UKM Medical Centre
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
      • Hospital Serdang
    • Petaling Jaya, Selangor, Malaysia, 46100
      • National Kidney Foundation (Malaysia)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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: Control group; Control group will be supplemented with placebo for 12 months.	Dietary supplement: Placebo; 2 x 150mg capsules daily
Active Comparator: Intervention group; The intervention arm will be supplemented with TRF for 12 months.	Dietary supplement: TRF; 2 x 150mg capsules daily; Other Names: Vitamin E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in inflammatory marker based on the mean change from baseline to 12 months.	Changes in biochemistry marker namely hsCRP (mg/dL)	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma lipids	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)	Baseline to 12 months
Changes in restless leg syndrome scoring	Based on restless leg syndrome questionnaire	Baseline to 12 months
Changes in anthropometry measures	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)	Baseline to 12 months
Changes in body composition	Body composition assessment pertaining to hydration status, lean tissue mass and fat mass is derived using a portable BIA device.	Baseline to 12 months
Changes in muscle strength	Handgrip strength (in kilogram) will be measured using hand held dynamometer	Baseline to 12 months
Changes in biochemistry parameters	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).	Baseline to 12 months
Changes in dietary intake	Dietary intake will be assessed using a 3-day 24-hr diet recalls to determine macro and micronutrient intake.	Baseline to 12 months
Changes in nutritional status	Patients will be screened with the Malnutrition Inflammation Score questionnaire to categorize their nutritional status.	Baseline to 12 months
Changes in qualify of life (QOL)	Subjects will be interviewed using SF-36 & KD-QOL questionnaire which will derive QOL score.	Baseline to 12 months
Changes in rate of hospitalisation	Difference in frequency of hospitalisation between the groups during the 12 months will be determined.	Baseline to 12 months
Changes in metabolomics analyses	Metabolomic analyses (using blood specimens) will be carried out to determine differences in metabolites between the groups.	Baseline to 12 months

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Universiti Putra Malaysia; National Kidney Foundation; Ministry of Health, Malaysia; Malaysia Palm Oil Board; PEMANDU
• Investigators: Principal Investigator: Tilakavati Karupaiah, PhD, National University of Malaysia

Publications and helpful links

General Publications

• 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.

Helpful Links

• Information on the parallel study conducted in USA by Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2017
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 14, 2020

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: September 21, 2016
• First Posted (Estimate): September 26, 2016

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin E; Hemodialysis; Tocotrienol
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E
• Other Study ID Numbers: NN-041-2015; NMRR-14-1859-23386 (Other Identifier: Medical Research and Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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