Patients undergoing chronic hemodialysis are at increased risk for cardiovascular disease,
attributed in part to increased oxidative stress, inflammation and dyslipidemia. Intervention
with a naturally occurring dietary supplement may improve certain biomarkers of inflammation
and oxidative stress and improve the lipid profile.
End stage renal disease (ESRD) patients who are undergoing hemodialysis (HD) have higher
levels of blood markers which the body makes in response to increased stress and injury. An
increase in these markers has been shown to be related to cardiovascular disease and death in
ESRD patients. It is believed that taking antioxidants (e.g. Vitamin E) may decrease these
markers. In a previous study in ESRD patients on HD, consumption of a Vitamin E
tocotrienol-rich fraction (TRF) was found to improve some of these markers. The current study
will follow a larger group of patients for a longer time period (1 year) and document effects
on additional markers
The study will document the extent to which supplementation with TRF will improve markers of
inflammation, oxidative stress as well as blood lipids in ESRD patients on chronic HD as
compared to a placebo. Additionally, the study will aim to document any improvement in
Restless Legs Syndrome - tingling sensation in the legs - (RLS) with TRF, based on a standard
The study will last for 15 months. At the start of the study basic patient information will
be evaluated related to their monthly dialysis labs, inflammation and oxidative stress
markers as well as general information about the patients in relation to their kidney
disease. Patients will then be randomized into one of two groups. One group will receive TRF,
daily, for 12 months while the second group will receive placebo, daily, for 12 months.
Capsules will be administered in the dialysis clinic/unit at the start of each dialysis
session (thrice weekly), while patients will be provided capsules to be consumed at home for
the remaining four days of each week.
During the 12 month treatment period, patients will be questioned every three months at their
dialysis units by study staff to obtain information on dialysis labs, medical condition,
hospitalizations, and to check to see if they are taking the study capsules.
As part of their routine standard care, patients will continue to have monthly blood draws.
For the purposes of this study, at each trimonthly blood draw, we will obtain additional
blood to examine the markers related to oxidative stress, inflammation and lipids. A blood
sample will also be collected at 15 months (3 months after patients stop taking capsules).
Therefore over the course of the entire study, blood will obtained at baseline and 3, 6, 9
and 12 months (plus the 15 month follow-up sample).
At each trimonthly blood draw including the follow-up visit at 15 months, patients will also
be verbally administered a Restless Legs Syndrome Questionnaire. In addition a dietitian
member of the research team will administer a 24 hr diet recall questionnaire
Sample size was based on inflammatory markers (hsCRp and IL-6) as reported in earlier studies
and a sample size of 175 per group was estimated to achieve a 80% power at p=0.05
significance level. Thus accounting for potential drop-outs over the 1 year of the study,
target is recruitment of 400 patients total (200 for each group) in Detroit, MI.
(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 Kuala Lumpur, Malaysia).
- Patient is willing and able to give informed consent for participation in the trial.
- Male or Female, aged 18 years and above. Undergoing chronic hemodialysis treatment for
more than 3 months (life expectancy > 1 year).
- Able and willing to comply with all trial requirements.
- Willing to allow his or her /Physician/Nephrologist/General Practitioner and
consultant, if appropriate, to be notified of participation in the trial.
- Participants who have participated in another research trial involving an
investigational product in the past 12 weeks.
- History of functional kidney transplant 6 months before study entry; anticipated live
donor kidney transplant over the study duration;
- Participants who are taking vitamin E- containing supplements >60 IU/d during the past
- History of poor adherence to hemodialysis or medical regimen
- Participants who are currently on active treatment for cancer, excluding basal cell
carcinoma of the skin
- Participants who have been diagnosed as HIV/AIDS and/or on the anti-HIV therapy. (HIV
seropositivity is not an exclusion criterion)
- Patients taking anti-inflammatory medication, except aspirin<325 mg/d, over the past
- Female participant who is pregnant, lactating or planning pregnancy during the course
of the trial
- Participants who are receiving nutritional support (i.e. enteral and intra-venous
- Patients using a temporary catheter for dialysis access at baseline or patients
receiving a graft/fistula within the 6-month study period
- More than two hospitalizations within the last 90 days or one hospitalization within
the 30 days preceding enrollment
- Any other significant disease or disorder which, in the opinion of their nephrologist,
may either put the participants at risk because of participation in the trial, or may
influence the result of the trial, or the participant's ability to participate in the