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| Name | Class |
|---|---|
| dsm-firmenich Switzerland AG | INDUSTRY |
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Multicenter, randomized, double-blinded, placebo-controlled clinical trial is focused on novel treatments for non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease. The primary objective of the study is to determine the clinical efficacy and safety of Vitamin E [(all-rac)-α-tocopheryl acetate] and Omega-3 fatty acid (DHA EE) compared to placebo on reducing liver fat content in participants with NAFLD. There is currently no approved drug treatment for NAFLD or NASH. While several new targets are being evaluated, they are not sufficiently powered to provide definitive data. There is, therefore, a need for well-designed, appropriately powered efficacy (phase 2) trials to define the utility of newer therapies for NAFLD. The combination of Vitamin E and DHA may provide optimal benefit for patients with NAFLD due to their associated mechanisms of action, namely Vitamin E's antioxidant action, preventing lipid oxidation of long-chain fatty acids such as DHA and thus preventing the propagation of free radicals and ROS.
Background information
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver and is defined by evidence of hepatic steatosis (via imaging or histology) and is not due to secondary liver fat accumulation from excessive alcohol consumption or hereditary disorders (e.g., Wilson's disease). NAFLD is most commonly associated with metabolic syndrome, consisting of obesity, insulin resistance, elevated blood pressure, and dyslipidemia. NAFLD is one of the most common causes of chronic liver disease, globally with a prevalence as high as 30% in Western countries. It includes a spectrum of diseases from steatosis to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver does not involve hepatocellular injury in the form of ballooning hepatocytes, whereas NASH is defined by steatosis, inflammation, and hepatocyte injury (ballooning) with or without fibrosis. The causes of NAFLD are likely due to a combination of genetic and physiologic factors, namely those that promote oxidative stress and inflammation such as metabolic syndrome, visceral adiposity, and changes in intestinal microbiota. NAFLD is significantly associated with increased risk of Type II Diabetes and cardiovascular disease and increased overall mortality compared to age-matched controls. There is currently no approved drug treatment for NAFLD or NASH. Dietary restrictions for weight loss and increased physical activity are the recommended therapies, albeit with limited success.
Investigational products
Vitamin E [(all-rac)-α-tocopheryl acetate]
Vitamin E is a fat-soluble vitamin that is synthesized naturally in plants in four tocopheryl forms: α, β, γ, and δ. All-rac-α-tocopheryl acetate has the highest biological activity in animal models, and it is the α-tocopheryl form that is used to prevent and treat Vitamin E deficiency in humans. Functionally, Vitamin E is an anti-oxidant and peroxyl radical scavenger. It is an inhibitor of lipid peroxidation and can also inhibit and modulate intracellular signaling molecules, e.g., protein kinase C, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. α-tocopheryl regulates gene expression of several intracellular enzymes such as 5-lipoxygenase and cyclooxygenase and has anti-inflammatory activity (i.e., decreasing cytokine release and plasma C reactive protein). It is also known to inhibit platelet adhesion and aggregation. \
DHA Ethyl Ester
Long-chain polyunsaturated fatty acid (LC-PUFA), docosahexaenoic acid (DHA) is an essential omega-3 fatty acid for brain, eye and cardiovascular development and health. It significantly reduces triglycerides (TGs), lowers heart rate, lowers blood pressure, and reduces the risk of cardiac death by an overall 8%. Both DHA and eicosapentaenoic acid (EPA) have anti-thrombotic, anti-inflammatory, and anti-oxidative properties. As NAFLD patients are at significantly greater risk of cardiovascular disease and higher overall mortality, the cardioprotective effects of DHA are significant and may be beneficial in the NAFLD population.
Potential mechanisms for DHA's effects in NAFLD include the reduction of TG synthesis via activation of peroxisome proliferator-activated receptors (PPAR-α and γ), which accelerates fatty acid oxidation in liver mitochondria. DHA is also known to have an integral role in maintaining and improving cell membrane fluidity, as a fatty acid that is incorporated into the phospholipids of the membrane, thereby optimizing surface receptors and signal transduction pathways in liver cells. The anti-inflammatory role of DHA in NAFLD may be mediated through activation of adiponectin secretion through adults with NAFLD. MRI-PDFF is also an appropriate technique to diagnose and stage disease in those with metabolic syndrome and NAFLD. The clinical trial is designed to test the combination of Vitamin E and DHA against placebo, to demonstrate efficacy and safety.
Rationale for conducting the clinical study
The combination of Vitamin E and DHA has not been tested in previous clinical trials of adults with NAFLD. This combination may provide optimal benefit for patients with NAFLD due to their associated mechanisms of action, namely Vitamin E's antioxidant action, preventing lipid oxidation of long-chain fatty acids such as DHA and thus preventing the propagation of free radicals and ROS. Vitamin E's protection of LC-PUFA DHA, therefore, assists it in maintaining cell membrane stability and optimal signaling. Their combined anti-inflammatory effects (e.g., inhibiting pro-inflammatory cytokines, increasing adiponectin, and producing docosanoids to resolve inflammation) may also be efficacious for those with metabolic syndrome and NAFLD. The combination of Vitamin E and DHA will correctly be used in this study to determine if a reduction in liver fat occurs after six months of co-administration, using a magnetic resonance imaging (MRI) technique, proton density fat fraction (PDFF). PDFF imaging is non-invasive and highly sensitive to detect liver steatosis in patients with NAFLD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin E (1000 mg) | Active Comparator | Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months. |
|
| DHA EE (1.89 g) | Active Comparator | DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). |
|
| DHA EE (1.89 g) and Vitamin E (1000 mg) | Active Comparator | DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months. |
|
| Placebo | Placebo Comparator | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin E [(all-rac)-α-tocopheryl acetate] | Dietary Supplement | Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hepatic Fat Fraction [%] Between of Vitamin E and DHA EE vs Placebo | A change in liver fat content relative to baseline between Vitamin E and DHA EE vs placebo. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). | Baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hepatic Fat Fraction [%] Between Vitamin E vs Placebo Arm | Change in liver fat content relative to baseline between Vitamin E vs placebo arm. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). | Baseline to 6 months |
| Change in Hepatic Fat Fraction [%] Between DHA EE vs Placebo Arm |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Naga P. Chalasani, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Liver Health | Chandler | Arizona | 85712 | United States | ||
| Arizona Liver Health |
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April, 2024
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| ID | Title | Description |
|---|---|---|
| FG000 | Vitamin E (1000 mg) | Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months. Vitamin E [(all-rac)-α-tocopheryl acetate]: Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 10, 2021 | Mar 10, 2023 |
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| Omega-3 fatty acid (DHA EE) | Dietary Supplement | DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) |
|
| Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate] | Combination Product | DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months |
|
|
| Placebo | Other | Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
Change in liver fat content relative to baseline between DHA EE vs placebo arm. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). |
| Baseline to 6 months |
| Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist Circumference. | Evaluation of baseline and 6 month measurements of waist circumference in the DHA EE and /or Vitamin E intervention over a 6 month period. | Baseline to 6 months |
| Change After 6 Months of DHA EE and /or Vitamin E Intervention in the Anthropometric Measure, Bodyweight. | Evaluation of baseline and 6-month measurements of body weight in the DHA EE and /or Vitamin E intervention over a 6 month period. | Baseline to 6 months |
| Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist-to-hip Ratio . | Evaluation of baseline and 6-month measurements of waist-to-hip ratio (the circumference of the waist divided by the circumference of the hips) in the DHA EE and /or Vitamin E intervention over a 6 month period. | Baseline to 6 months |
| Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Body Mass Index (BMI) | Evaluation of baseline and 6-month measurements of body mass index (BMI) in the DHA EE and /or Vitamin E intervention over a 6 month period. | Baseline to 6 months |
| Change in Insulin Levels to Determine Insulin Resistance | Baseline to 6 months |
| Change in Liver Enzymes (ALT) in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: alanine transaminase (ALT) in the DHA EE and /or Vitamin E intervention over a 6 month period value at (6 months minus value at baseline). | Baseline to 6 months |
| Change in Liver Enzymes (AST) in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: aspartate aminotransferase (AST) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Liver Enzymes Bilirubin in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: Bilirubin in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Liver Enzymes Alkaline Phosphatase in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: Alkaline Phosphatase in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Fibrosis-4 (FIB-4) Score | The formula for FIB-4 is: Age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). A value of FIB-4 below 1.30 is considered as low risk for advanced fibrosis; a value of FIB-4 over 2.67 is considered as high risk for advanced fibrosis | Baseline to 6 months |
| Change in Plasma Vitamin E Concentration | Evaluation of baseline and 6-month plasma Vitamin E concentration in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Plasma DHA EE Concentration | Evaluation of baseline and 6-month plasma DHA EE concentration in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Lipid Profile (HDL-C) | Evaluation of baseline and 6-month lipid profile (HDL-C) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Lipid Profile (Low Density Lipoprotein (LDL-C)) | Evaluation of baseline and 6-month lipid profile (low density lipoprotein (LDL-C))in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Lipid Profile (Triglycerides) | Evaluation of baseline and 6-month lipid profile (TGs)in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Lipid Profile (Oxidized LDL) | Evaluation of baseline and 6-month lipid profile (oxidized LDL) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Health Related Quality of Life Score (Short Form (SF-36)) | Evaluation of baseline and 6-month quality of life score (SF-36) in the DHA EE and /or Vitamin E intervention over a 6 month period (value at 6 months minus value at baseline). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability | Baseline to 6 months |
| Change in Dietary Intake Levels of Long-chain Polyunsaturated Fatty Acids (LC-PUFA ) (i.e. DHA and EPA) as Measured by the Food Frequency Questionnaire (FFQ) | Evaluation of baseline and 6-month dietary intake levels of LC-PUFA (i.e. DHA and EPA) as measured by the Food Frequency Questionnaire (FFQ)in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Inflammatory Markers (Cytokeratin 18 (CK-18)) | Evaluation of baseline and 6-month inflammatory markers (cytokeratin 18) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Inflammatory Markers (IL-1β) | Evaluation of baseline and 6-month inflammatory markers (IL-1β) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Change in Inflammatory Markers (TNFα) | Evaluation of baseline and 6-month inflammatory markers (TNFα) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Baseline to 6 months |
| Tucson |
| Arizona |
| 85712 |
| United States |
| Arkansas Gastroenterology | North Little Rock | Arkansas | 72117 | United States |
| Inland Empire Clinical Trials, LLC | Rialto | California | 92377 | United States |
| Integrity Clinical Research LLC | Doral | Florida | 33166 | United States |
| Indago Research and Health Center, Inc. | Hialeah | Florida | 33012 | United States |
| Florida Research Institute | Lakewood Rch | Florida | 34211 | United States |
| Advanced Pharma CR LLC | Miami | Florida | 33147 | United States |
| Med-Care Research | Miami | Florida | 33165 | United States |
| Summit Clinical Research LLC | Athens | Georgia | 30607 | United States |
| Indiana University School of Medicine | Indianapolis | Indiana | 46202 | United States |
| M3 Wake Research Associates | Raleigh | North Carolina | 27612 | United States |
| Centex Studies, Inc. | Houston | Texas | 77058 | United States |
| Liver Specialists of Texas/Mt. Olympus Medical Research | Houston | Texas | 77479 | United States |
| American Research Corporation at the Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| DHA EE (1.89 g) |
DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) |
| FG002 | DHA EE (1.89 g) and Vitamin E (1000 mg) | DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months. Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate]: DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months |
| FG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
| COMPLETED |
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| NOT COMPLETED |
|
|
Vitamin E ad DHA EE groups not consistent with participant workflow due to two subjects not completing MRI.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vitamin E (1000 mg) | Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months. Vitamin E [(all-rac)-α-tocopheryl acetate]: Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months |
| BG001 | DHA EE (1.89 g) | DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) |
| BG002 | DHA EE (1.89 g) and Vitamin E (1000 mg) | DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months. Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate]: DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months |
| BG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Hepatic Fat Fraction [%] Between of Vitamin E and DHA EE vs Placebo | A change in liver fat content relative to baseline between Vitamin E and DHA EE vs placebo. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | Percentage of liver fat | Baseline to 6 months |
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| Secondary | Change in Hepatic Fat Fraction [%] Between Vitamin E vs Placebo Arm | Change in liver fat content relative to baseline between Vitamin E vs placebo arm. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | Percentage of liver fat | Baseline to 6 months |
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| Secondary | Change in Hepatic Fat Fraction [%] Between DHA EE vs Placebo Arm | Change in liver fat content relative to baseline between DHA EE vs placebo arm. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | Percentage of liver fat | Baseline to 6 months |
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| Secondary | Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist Circumference. | Evaluation of baseline and 6 month measurements of waist circumference in the DHA EE and /or Vitamin E intervention over a 6 month period. | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | centimeters (cm) | Baseline to 6 months |
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| Secondary | Change After 6 Months of DHA EE and /or Vitamin E Intervention in the Anthropometric Measure, Bodyweight. | Evaluation of baseline and 6-month measurements of body weight in the DHA EE and /or Vitamin E intervention over a 6 month period. | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | kilogram (kg) | Baseline to 6 months |
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| Secondary | Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist-to-hip Ratio . | Evaluation of baseline and 6-month measurements of waist-to-hip ratio (the circumference of the waist divided by the circumference of the hips) in the DHA EE and /or Vitamin E intervention over a 6 month period. | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | ratio | Baseline to 6 months |
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| Secondary | Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Body Mass Index (BMI) | Evaluation of baseline and 6-month measurements of body mass index (BMI) in the DHA EE and /or Vitamin E intervention over a 6 month period. | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | kg/m^2 | Baseline to 6 months |
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| Secondary | Change in Insulin Levels to Determine Insulin Resistance | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | ulU/mL | Baseline to 6 months |
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| Secondary | Change in Liver Enzymes (ALT) in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: alanine transaminase (ALT) in the DHA EE and /or Vitamin E intervention over a 6 month period value at (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | U/L | Baseline to 6 months |
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| Secondary | Change in Liver Enzymes (AST) in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: aspartate aminotransferase (AST) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | U/L | Baseline to 6 months |
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| Secondary | Change in Liver Enzymes Bilirubin in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: Bilirubin in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | mg/dL | Baseline to 6 months |
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| Secondary | Liver Enzymes Alkaline Phosphatase in the DHA EE and /or Vitamin E Intervention Over a 6 Month Period. | Evaluation of baseline and 6-month liver enzymes: Alkaline Phosphatase in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | U/L | Baseline to 6 months |
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| Secondary | Change in Fibrosis-4 (FIB-4) Score | The formula for FIB-4 is: Age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). A value of FIB-4 below 1.30 is considered as low risk for advanced fibrosis; a value of FIB-4 over 2.67 is considered as high risk for advanced fibrosis | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | units on a scale | Baseline to 6 months |
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| Secondary | Change in Plasma Vitamin E Concentration | Evaluation of baseline and 6-month plasma Vitamin E concentration in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | ng/mL | Baseline to 6 months |
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| Secondary | Change in Plasma DHA EE Concentration | Evaluation of baseline and 6-month plasma DHA EE concentration in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | ug/mL | Baseline to 6 months |
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| Secondary | Change in Lipid Profile (HDL-C) | Evaluation of baseline and 6-month lipid profile (HDL-C) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | mg/dL | Baseline to 6 months |
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| Secondary | Change in Lipid Profile (Low Density Lipoprotein (LDL-C)) | Evaluation of baseline and 6-month lipid profile (low density lipoprotein (LDL-C))in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | mg/dL | Baseline to 6 months |
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| Secondary | Change in Lipid Profile (Triglycerides) | Evaluation of baseline and 6-month lipid profile (TGs)in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | mg/dL | Baseline to 6 months |
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| Secondary | Change in Lipid Profile (Oxidized LDL) | Evaluation of baseline and 6-month lipid profile (oxidized LDL) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | U/L | Baseline to 6 months |
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| Secondary | Change in Health Related Quality of Life Score (Short Form (SF-36)) | Evaluation of baseline and 6-month quality of life score (SF-36) in the DHA EE and /or Vitamin E intervention over a 6 month period (value at 6 months minus value at baseline). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | score on a scale | Baseline to 6 months |
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| Secondary | Change in Dietary Intake Levels of Long-chain Polyunsaturated Fatty Acids (LC-PUFA ) (i.e. DHA and EPA) as Measured by the Food Frequency Questionnaire (FFQ) | Evaluation of baseline and 6-month dietary intake levels of LC-PUFA (i.e. DHA and EPA) as measured by the Food Frequency Questionnaire (FFQ)in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | mg per day | Baseline to 6 months |
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| Secondary | Change in Inflammatory Markers (Cytokeratin 18 (CK-18)) | Evaluation of baseline and 6-month inflammatory markers (cytokeratin 18) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | U/L | Baseline to 6 months |
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| Secondary | Change in Inflammatory Markers (IL-1β) | Evaluation of baseline and 6-month inflammatory markers (IL-1β) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | pg/mL | Baseline to 6 months |
| ||||||||||||||||||||||||||||||
| Secondary | Change in Inflammatory Markers (TNFα) | Evaluation of baseline and 6-month inflammatory markers (TNFα) in the DHA EE and /or Vitamin E intervention over a 6 month period (6 months minus value at baseline). | Participants analyzed varies from participant workflow due to inconsistencies in what was able to be collected at differing sites and timepoints | Posted | Mean | Standard Deviation | pg/mL | Baseline to 6 months |
|
6 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vitamin E (1000 mg) | Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months. Vitamin E [(all-rac)-α-tocopheryl acetate]: Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months | 0 | 34 | 0 | 34 | 6 | 34 |
| EG001 | DHA EE (1.89 g) | DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) | 0 | 34 | 0 | 34 | 17 | 34 |
| EG002 | DHA EE (1.89 g) and Vitamin E (1000 mg) | DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months. Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate]: DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months | 0 | 67 | 1 | 67 | 18 | 67 |
| EG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. | 1 | 70 | 1 | 70 | 25 | 70 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrest | Cardiac disorders | Systematic Assessment |
| ||
| Chest pain | General disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Nervous system disorders | Systematic Assessment |
| ||
| Hypertonic Bladder | Renal and urinary disorders | Systematic Assessment |
| ||
| Pyrexia | Nervous system disorders | Systematic Assessment |
| ||
| Meniscus injury | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Rib fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Upper limb fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Palpitations | Cardiac disorders | Systematic Assessment |
| ||
| Heart valve incompetence | Cardiac disorders | Systematic Assessment |
| ||
| Bell's Palsy | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Diverticulum | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dermatitis allergic | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dermatitis contact | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Cholelithiasis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Food poisioning | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Rectal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Chronic gastritis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Eosinophilic esophagitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| abdominal distension | Gastrointestinal disorders | Systematic Assessment |
| ||
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| abdominal pain lower | Gastrointestinal disorders | Systematic Assessment |
| ||
| abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Eructation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Esophageal ulcer | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Edema peripheral | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Diabetes mellitus type 2 | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Headache | General disorders | Systematic Assessment |
| ||
| Migraine | General disorders | Systematic Assessment |
| ||
| Deafness | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Hepatobiliary disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Hepatobiliary disorders | Systematic Assessment |
| ||
| Liver function test increased | Hepatobiliary disorders | Systematic Assessment |
| ||
| Bronchitis | Infections and infestations | Systematic Assessment |
| ||
| Ear infection | Infections and infestations | Systematic Assessment |
| ||
| Gastroenteritis | Infections and infestations | Systematic Assessment |
| ||
| Hordeolum | Infections and infestations | Systematic Assessment |
| ||
| Mastoiditis | Infections and infestations | Systematic Assessment |
| ||
| Pharyngitis | Infections and infestations | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
| ||
| Tooth abscess | Infections and infestations | Systematic Assessment |
| ||
| Tooth infection | Infections and infestations | Systematic Assessment |
| ||
| Contusion | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Foreign body in eye | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Blood cholesterol increased | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Remnant hyperlipidemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Heavy menstrual bleeding | Reproductive system and breast disorders | Systematic Assessment |
| ||
| Blood glucose increased | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Fibromyalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Chalazion | Eye disorders | Systematic Assessment |
| ||
| Neuropathy peripheral | Vascular disorders | Systematic Assessment |
| ||
| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Gout | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Night sweats | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Neoplasm skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Insomnia | General disorders | Systematic Assessment |
| ||
| Desmoid tumor | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Hypothyroidism | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dysuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Nephrolithiasis | Renal and urinary disorders | Systematic Assessment |
| ||
| Endometriosis | Reproductive system and breast disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| COVID-19 | Infections and infestations | Systematic Assessment |
| ||
| Hepatitis C | Infections and infestations | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Naga Chalasani, MD | Indiana University School of Medicine | (317) 278-0414 | nchalasa@iu.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2022 | Mar 10, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D014810 | Vitamin E |
| D015525 | Fatty Acids, Omega-3 |
| ID | Term |
|---|---|
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months).
Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months)
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG002 | DHA EE (1.89 g) | DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) |
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months). Omega-3 fatty acid (DHA EE): DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months) |
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|
| OG003 | Placebo | Matching soybean oil placebo (3 capsules) of all arms daily for 6 months. Placebo: Matching soybean placebo (3 capsules) of all arms daily for 6 months. |
|
|