Clinical trial NCT02358967: Palm Tocotrienols in Chronic Hemodialysis (USA)
Official title: Palm Tocotrienols in Chronic Hemodialysis (PATCH Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Chronic Kidney Disease
Keywords: ESRD
dyslipidemia
oxidative stress
inflammation
Hemodialysis
CKD
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: DaVita Dialysis
name: Great Lakes Dialysis, LLC
name: National University of Malaysia
name: Universiti Putra Malaysia
name: Ministry of Health, Malaysia
name: National Kidney Foundation, United States
name: PEMANDU
name: Henry Ford Hospital
name: Kidney Foundation Hospital and Research Institute, Bangladesh
name: Fortis Hospital, India
First posted: 2015-02-09
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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 questionnaire.

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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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 30 days
* 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 30 days
* 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 route)
* 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 trial.

Primary outcomes:
measure: Inflammatory markers
timeFrame: Every 3 months, upto 15 months
Secondary outcomes:
measure: Plasma lipids
timeFrame: Every 3 months, upto 15 months
measure: Restless Legs Syndrome
timeFrame: Every 3 months, upto 15 months
measure: Dietary history
timeFrame: Every 3 months, upto 15 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
Study officials:
affiliation: Wayne State University
name: Pramod Khosla, 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: Daud ZA, Tubie B, Adams J, Quainton T, Osia R, Tubie S, Kaur D, Khosla P, Sheyman M. Effects of protein and omega-3 supplementation, provided during regular dialysis sessions, on nutritional and inflammatory indices in hemodialysis patients. Vasc Health Risk Manag. 2012;8:187-95. doi: 10.2147/VHRM.S28739. Epub 2012 Mar 20.