End Stage Cardiac Failure, End Stage Liver Disease, Healthy Subjects, Morbid Obesity, Pulmonary Failure, Recalcitrant Epilepsy Requiring Surgery
Conditions
Brief summary
Levels of tocotrienol in human tissues following supplementation is not currently known. The objective of this present study is to determine the levels of this form of vitamin E in the human tissues such as skin, heart, lung, liver, adipose tissue, Brain and cerebrospinal fluid (CSF) following oral supplementation
Detailed description
In nature, there are eight members in the vitamin E family: a-, b-, g- and d-TCP, and a-, b-, g- and d-tocotrienol (TCT). Vitamin E research has developed highly asymmetrically. Out of the 25,000+ papers on vitamin E in the PubMed, 99% deal with tocopherols. Recent research has demonstrated the lack of cancer-preventive effects and potential adverse health consequences of tocopherol (6). As a result, more attention has been turned towards non-tocopherol forms of vitamin E (16). Palm oil represents a major source of natural TCT. TCT possess powerful neuroprotective, antioxidant, anti-cancer and cholesterol lowering properties that often differ from the properties of TCP (15). During the last five years, our and other laboratories have reported several striking beneficial properties of tocotrienols in experimental settings. One major concern that limits enthusiasm for tocotrienol for humans is the report that the vitamin E transporting protein, tocopherol-transport protein (TTP), has a very low affinity to transport tocotrienol. Using TTP-knock out mice, we have recently demonstrated that oral TCT is effectively carried to vital organs and that such transport can take place independent of TTP. With that background, the purpose of this project is to test the hypothesis that orally supplemented tocotrienol reaches the vital organs of humans.
Interventions
DIETARY_SUPPLEMENTTo surgery patients, Tocopherol capsules.
200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily
DIETARY_SUPPLEMENTTocotrienol to healthy subjects.
200 mg to take orally two times a day (400 mg a day).
DIETARY_SUPPLEMENTTo surgery patients, Tocotrienol capsules.
200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily
Sponsors
Carotech Inc.
Chandan K Sen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Aim 1 Surgical candidate with a surgery schedule date with a time period of 4-24 weeks (\<4 weeks will be excluded; last dose until 24h before surgery) In Aim 1 we expect to have patients, with diverse co-morbidity and medication conditions. Patient Selection: Because of limitation in obtaining healthy human tissues (as in Aim 2), we plan to obtain these tissues from patients who are scheduled for the following surgeries for subjects in group one: Heart Heart Transplant Heart Failure- Biopsy taken from diseased heart Lung Lung Transplant, Lung-wedge/resection, Lobectomy Cancer- Tissue sample taken from removed lung or resected portion of lung Liver Liver Transplant, Biopsy, Resection Hepatic Malignancy- Biopsy taken from resected portion of liver Adipose Tissue Panniculectomy Excessive Tissue of the Abdomen Brain & CSF Epilepsy Excised brain tissue and cerebrospinal fluid To ensure higher enrollment we are not controlling for age of subjects as long as the subjects are 21 years of age or older. Inclusion Criteria Aim 1: * age 21 and older * good health * non- smoker * no current medications * non- pregnant or non-breastfeeding * no previous use of OTC medications or other form of supplements containing vitamin-E. Inclusion Criteria Aim 2: * age 21 - 40 years * good health * non- smoker * no current medications * non- pregnant or non-breastfeeding * no previous use of OTC medications or other form of supplements containing vitamin-E.
Exclusion criteria
Aim 1: * Long-term use of OTC medications containing vitamin-E or current vitamin-E supplements * Scheduled surgery date lesser than 4 weeks or greater than 24 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | After at least 1 month of supplementation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1- Surgical + Tocotrienol 200 mg Surgical Subjects will recieve either Tocotrienol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | 40 |
| Arm 2 - Surgical + Tocopherol 200 mg Surgical Subjects will recieve Tocopherol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | 15 |
| Arm 3- Healthy + Tocotrienol 200 mg Healthy Subjects will recieve either Tocotrienol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | 25 |
| Total | 80 |
Baseline characteristics
| Characteristic | Total | Arm 1- Surgical + Tocotrienol 200 mg | Arm 2 - Surgical + Tocopherol 200 mg | Arm 3- Healthy + Tocotrienol 200 mg |
|---|---|---|---|---|
| Age, Continuous | 40.37 years STANDARD_DEVIATION 4.61 | 49.37 years STANDARD_DEVIATION 12.81 | 54 years STANDARD_DEVIATION 11.56 | 30.24 years STANDARD_DEVIATION 8.59 |
| Region of Enrollment United States | 80 participants | 40 participants | 15 participants | 25 participants |
| Sex: Female, Male Female | 43 Participants | 20 Participants | 10 Participants | 13 Participants |
| Sex: Female, Male Male | 37 Participants | 20 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 15 | 0 / 25 |
| serious Total, serious adverse events | 0 / 40 | 0 / 15 | 0 / 25 |
Outcome results
Primary
The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks)
Time frame: After at least 1 month of supplementation
Population: Box plots were used to determine outliers defined as values . the 75th percentile plus 1.5 times the IQR or values , the 25th percentile minus 1.5 times the IQR (20). Outliers were identified and it was determined that laboratory procedural errors were the cause and thus removed from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Surgical, Adipose | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 9.94 nmol/g | Standard Deviation 6.9 |
| Arm 1: Surgical, Brain | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 1.29 nmol/g | Standard Deviation 1.06 |
| Arm 1: Surgical, Heart | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 5.37 nmol/g | Standard Deviation 4.28 |
| Arm 1: Surgical, Liver | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 0.42 nmol/g | Standard Deviation 0.43 |
| Arm 2: Surgical, Adipose | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 28.6 nmol/g | Standard Deviation 20.7 |
| Arm 2: Surgical, Brain | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 50.5 nmol/g | Standard Deviation 17.2 |
| Arm 2: Surgical, Heart | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 31.9 nmol/g | Standard Deviation 20 |
| Arm 2: Surgical, Liver | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 64.3 nmol/g | Standard Deviation 14.9 |
| Arm 3: Healthy, Blood, Week 0 | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 0.01 nmol/g | Standard Deviation 0.02 |
| Arm 3: Healthy, Blood, Week 6 | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 1.9 nmol/g | Standard Deviation 0.7 |
| Arm 3: Healthy, Skin, Week 12 | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 1.5 nmol/g | Standard Deviation 1.8 |
| Arm 3: Healthy, Skin, Week 0 | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 2.5 nmol/g | Standard Deviation 3 |
| Arm 3: Healthy, Blood, Week 12 | The Levels of TCT in the Tissues of Non-healthy Subjects and in the Tissue of Healthy Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) | 0.03 nmol/g | Standard Deviation 0.1 |