Palm Tocotrienols in Chronic Hemodialysis (Malaysia) (PATCH)

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Chronic Kidney Failure

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: TRF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Control group will be supplemented with placebo for 12 months. | Dietary Supplement: Placebo<br>* 2 x 150mg capsules daily<br>|
| Active Comparator: Intervention group<br>The intervention arm will be supplemented with TRF for 12 months. | Dietary Supplement: TRF<br>* 2 x 150mg capsules daily<br>* Other names: Vitamin E;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Tocotrienol, Vitamin E