Hypercholesterolemia
Conditions
Keywords
Cholesterol
Brief summary
Elevated blood cholesterol, and particularly LDL cholesterol, is a risk factor for heart disease. Tocotrienols are naturally-occurring compounds in foods that may have beneficial effects on blood cholesterol. Tocotrienols are members of the vitamin E family, and are found in barley, oats, rye, coconut oil and rice bran oil, but the richest source of tocotrienols is palm oil. Certain of these tocotrienols have been shown to be effective in lowering LDL (or 'bad') cholesterol, with no adverse effects on the HDL (or 'good') cholesterol. The purpose of this study is to determine the effects of a palm-oil derived tocotrienol supplement on blood cholesterol, and particularly LDL cholesterol, in individuals who are taking statins, and have either elevated or normal cholesterol levels. Study subjects will consume a palm-oil derived supplement of tocotrienol for 3 months to determine its effects on LDL cholesterol.
Detailed description
Both tocotrienols and tocopherols, whose derivatives are in eight different isoforms, are closely related structurally. Tocopherols are generally present in common vegetable oils (i.e. soy, canola). However, tocotrienols are concentrated in cereal grains (ie. oat, barley, and rye, rice bran), with the highest level found in crude palm oil. The development of new cholesterol-lowering agents has been given more and more attention by pharmaceutical companies due to the strong relationship between cholesterol and atherosclerosis. Tocotrienols, especially δ- and γ-tocotrienols, were shown to be effective nutritional agents to treat high cholesterol in recent research programs. In particular, γ-tocotrienol appears to inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase at a posttranscriptional level and there is some evidence that tocopherols antagonize this effect. Therefore, the current study is designed to demonstrate that treatment with a tocotrienol-enriched fraction of palm oil for a three month period will lead to a significant reduction in LDL cholesterol with no effect on HDL cholesterol in patients whose cholesterol level is not adequately controlled in spite of statins. This objective will be achieved utilizing a simple three arm randomized placebo-controlled trial in a total of 99 subjects After acclimation to a step I AHA diet and no supplemental vitamin E in the diet, subjects will be given either a placebo capsule or a tocotrienol (120mg or 240mg) capsule in addition to their statin medications
Interventions
DRUGGamma Delta Tocotrienols - Low Dose
250 mg capsule containing 63 mg Gamma Delta Tocotrienols 2x/day for 12 weeks.
DRUGGamma Delta Tocotrienols - High Dose
250 mg capsule containing 127 mg Gamma Delta Tocotrienols 2x/day for 12 weeks.
DRUGSugar Pill
250 mg Placebo capsule containing 50% medium chain triglycerides and 50% glycerin 2x/day for 12 weeks.
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Able to read, speak, and understand English * Male or female, 35-70 years old (inclusive) * Total Fasting Plasma Cholesterol of \>180 mg/dl * Currently taking statin medications. * Willing to maintain AHA Step 1 diet for the duration of the study.
Exclusion criteria
* Any subject who is taking vitamin E supplements or taking any antibiotics or other medication or dietary supplement which could interfere with the action of tocotrienols. * Any subject who is taking cholesterol lowering medications other than statins. * Any subject who has lost \>5% of their body weight during the past 3 months. * Any subjects with a history of gastrointestinal surgery, diabetes mellitus, or other serious medical condition, such as chronic hepatitis or renal disease, bleeding disorder, congestive heart disease, chronic diarrhea disorders, myocardial infarction, coronary artery bypass graft, angioplasty within 6 months prior to screening, current diagnosis of uncontrolled hypertension (defined as BP \>160mmHg, diastolic BP\>95mmHg), active or chronic gastrointestinal disorders, bulimia, anorexia, laxative abuse, or endocrine diseases (except thyroid disease requiring medication) as indicated by medical history or routine physical examination. * Major surgery within 12 weeks prior to subject randomization and/or screening, especially cardiac surgery * Is currently a smoker who has a therapeutic plan to quit smoking anytime during the study period; or if not a current smoker, has quit smoking within the past 3 months. * Known HIV positive or known immunocompromised condition (e.g. MV, organ transplantation, treatment with immunosuppressant medications). * Clinical evidence of current malignancy with the exception of basal cell or squamous cell carcinoma of the skin and cervical intraepithelial neoplasia. * Currently receiving systemic chemotherapy and/or radiotherapy. * Active bleeding. * Subject has any disorder (excluding illiteracy or visual impairment) that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. * In the opinion of the study investigator has a risk of non-compliance with study procedures, or cannot read, understand or complete study related materials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL Cholesterol Over Time Between the 3 Groups | Baseline and 12 weeks | Mixed-effects regression models will be used to evaluate the change in LDL cholesterol over time between the 3 groups |
Countries
United States
Participant flow
Recruitment details
The enrollment period was 3/22/2011 - 11/13/2015 and took place in a private setting the clinic located at the site.
Pre-assignment details
Thirteen subjects with cholesterol level (\>180 mg/dl), aged 37-64, taking statins drug at the time were to be assigned to the low dose arm (TRF 63 mg), high dose arm (RTF 127 mg) or control (sugar pill) for 12 weeks. Randomization was not performed due to limited subjects recruited.
Participants by arm
| Arm | Count |
|---|---|
| Pre-Randomization Thirteen enrolled subjects were to be assigned to the low dose arm (TRF 63 mg), high dose arm (RTF 127 mg) or control (sugar pill). Randomization was not performed prior to study termination. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | unable to obtain the drug at start | 13 |
Baseline characteristics
| Characteristic | Pre-Randomization |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change in LDL Cholesterol Over Time Between the 3 Groups
Mixed-effects regression models will be used to evaluate the change in LDL cholesterol over time between the 3 groups
Time frame: Baseline and 12 weeks
Population: Randomization was not performed prior to study termination