Clinical trial NCT02913690: Palm Tocotrienols in Chronic Hemodialysis (Malaysia) (PATCH)
Official title: Effects of Dietary Supplementation Using Palm Tocotrienols in Chronic Hemodialysis (PATCH) Patients - A Multicenter Study Evaluating Markers of Inflammation, Oxidative Stress and Blood Lipids
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Kidney Failure
Keywords: Hemodialysis
Tocotrienol
Vitamin E
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: Universiti Putra Malaysia
name: Malaysia Palm Oil Board
name: PEMANDU
name: National Kidney Foundation, United States
name: Ministry of Health, Malaysia
First posted: 2016-09-26
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Improvement in inflammatory marker based on the mean change from baseline to 12 months.
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Changes in plasma lipids
timeFrame: Baseline to 12 months
measure: Changes in restless leg syndrome scoring
timeFrame: Baseline to 12 months
measure: Changes in anthropometry measures
timeFrame: Baseline to 12 months
measure: Changes in body composition
timeFrame: Baseline to 12 months
measure: Changes in muscle strength
timeFrame: Baseline to 12 months
measure: Changes in biochemistry parameters
timeFrame: Baseline to 12 months
measure: Changes in dietary intake
timeFrame: Baseline to 12 months
measure: Changes in nutritional status
timeFrame: Baseline to 12 months
measure: Changes in qualify of life (QOL)
timeFrame: Baseline to 12 months
measure: Changes in rate of hospitalisation
timeFrame: Baseline to 12 months
measure: Changes in metabolomics analyses
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: UKM Medical Centre
state: Cheras
city: Kajang
country: Malaysia
facility: Hospital Serdang
state: Selangor
city: Petaling Jaya
country: Malaysia
facility: National Kidney Foundation (Malaysia)
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
Study officials:
affiliation: National University of Malaysia
name: Tilakavati Karupaiah, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.