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| ID | Type | Description | Link |
|---|---|---|---|
| 5U01AA026817-04 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Cedars-Sinai Medical Center | OTHER |
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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The proposed of this randomized, double blinded, placebo-controlled study is to assess the effect of SAMe compared to placebo in patients with alcoholic cirrhosis Child Class A and B. The primary objective of the study is to test relationship between SAMe (S-adenosylmethionine) supplement on liver function. The hypothesis is that SAMe supplement will improve liver function in patients with alcoholic liver disease. The improvement in liver function will lead to the reduction in all-cause mortality in patients with alcoholic cirrhosis in those who receive SAMe supplement when compared to those receiving placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Alcoholic Cirrhosis on placebo |
|
| 1,200 mg SAMe | Experimental | SAMe supplement (SAMe 400 mg tablet), 2 tablets in the morning before breakfast and one tablet in the evening before dinner (a total dose of 1,200 mg daily) for 24 months |
|
| Non-drinking Controls | No Intervention | Non-drinking healthy controls |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 2 tablets of placebo in the morning before breakfast and one tablet of placebo in the evening before dinner for 24 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| SAMe supplement's effect on all-cause mortality | The hypothesis is that SAMe supplement will improve liver function in patients with alcoholic liver disease. The improvement in liver function will lead to the reduction in all-cause mortality in patients with alcoholic cirrhosis in those who receive SAMe supplement when compared to those receiving placebo. | Baseline to end of 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| SAMe supplement's effect on intestinal permeability function, as defined by serum lipopolysaccharides (LPS) | The function of intestinal permeability will be evaluated by testing serum lipopolysaccharides (LPS) in patients who receive SAMe compared to those who receive placebo. Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. | baseline to end of 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory outcome - identify who will improve their liver functions by taking the SAMe supplement amongst those that have been diagnosed with alcoholic cirrhosis (Child-Pugh score of A or B). | The metabolic profiling of the serum and urine will be collected by those in the study who received the SAMe supplement and will be used as the surrogates for this prediction. | baseline to 24 months |
Inclusion criteria for patients with alcoholic cirrhosis
Inclusion criteria for healthy control :
) individuals 18 to 70 years old (2) able to provide informed consent (3) subjects do not consume any alcohol or those who drink < 50 grams per day on average in women and < 80 grams per day on average in men (4) subjects are healthy without underlying acute or chronic medical conditions.
Exclusion criteria for patients with alcoholic cirrhosis
Exclusion criteria for all healthy control participants:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maggie Hesler, B.S | Contact | (317) 988-4545 | mshesler@iu.edu |
| Name | Affiliation | Role |
|---|---|---|
| Suthat Liangpunsakul, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Recruiting | Los Angeles | California | 90048 | United States |
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| ID | Term |
|---|---|
| D008104 | Liver Cirrhosis, Alcoholic |
| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008108 | Liver Diseases, Alcoholic |
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| ID | Term |
|---|---|
| D012436 | S-Adenosylmethionine |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D008715 | Methionine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| SAMe 400 mg tablet | Drug | SAMe supplement (SAMe 400 mg tablet), 2 tablets in the morning before breakfast and one tablet in the evening before dinner (a total dose of 1,200 mg daily) for 24 months |
|
| SAMe supplement's effect on cellular oxidative stress and/or endoplasmic reticulum (ER) stress, as defined by mitochondrial DNA | Cellular oxidative stress and/or endoplasmic reticulum (ER) stress will be evaluated by measuring the levels of mitochondrial DNA in the blood of patients who receive SAMe compared to those who receive placebo. | baseline to 24 months |
| SAMe supplement's effect on liver deuteriation | determining Proportion of subjects undergoing liver transplantation in patients who receive SAMe compared to those who receive placebo | baseline to 24 months |
| SAMe supplement's effect on liver developing cancer | Proportion of subjects developing new onset hepatocellular carcinoma in patients who receive SAMe compared to those who receive placebo | baseline to 24 months |
| SAMe supplement's effect on infections of the liver | Proportion of subjects with infection/sepsis (other than SBP) in patients who receive SAMe compared to those who receive placebo | baseline to 24 months |
| SAMe supplement's effect on other parts of the body | capture safety-related endpoints by determining proportion of patients with nausea and emesis, proportion of subjects with unexplained diarrhea in patients receive SAMe compared to those who receive placebo. | baseline to 24 months |
| SAMe supplement's effects on intestinal permeability function, as defined by soluble(s) CD14 | The function of intestinal permeability will be evaluated by testing soluble(s) CD14 in patients who receive SAMe compared to those who receive placebo. sCD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa). | baseline to 24 months |
| SAMe supplement's effects on intestinal permeability function, as defined by soluble(s) CD163 | The function of intestinal permeability will be evaluated by testing soluble(s) CD163 in patients who receive SAMe compared to those who receive placebo. CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163). | baseline to 24 months |
| SAMe supplement's effects on cellular oxidative stress and/or endoplasmic reticulum (ER) stress, as defined by cytochrome P450 2E1 levels | Levels of cellular oxidative stress and/or endoplasmic reticulum (ER) stress will be evaluated by measuring the levels of cytochrome P450 2E1 (CYP2E1) enriched microparticles in patients who receive SAMe compared to those who receive placebo.CYP2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. | baseline to 24 months |
| Indiana University Hospital | Recruiting | Indianapolis | Indiana | 46202 | United States |
|
| D005355 |
| Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020751 | Alcohol-Induced Disorders |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D000241 |
| Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |