A Feasibility Trial of OCM Supplements for the Treatment of NAFLD

Study Overview
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Brief Summary
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The purpose of the study is to assess the feasibility of a trial to test the effects of homocysteine (Hcy) lowering supplements in patients with NAFLD. NAFLD patients will be asked to take Hcy lowering supplements (Vitamin B12, Folate, Vitamin B6, and Betaine) daily for 12 weeks. Over the course of approximately 12 to 13 weeks, participants will complete two in person visits and two phone visits to complete activities such as physical exam, fibroscan, blood draws, and questionnaires.

Detailed Description
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The purpose of the study is to assess the feasibility of a trial to test the effects of homocysteine (Hcy) lowering supplements in patients with NAFLD. NAFLD patients will be asked to take Hcy lowering supplements (Vitamin B12, Folate, Vitamin B6, and Betaine) daily for 12 weeks. Over the course of approximately 12 to 13 weeks, participants will complete two in person visits and two phone visits. During the in person visits NAFLD participants will complete the following activities: Review medical history Physical examination Vital signs (blood pressure, heart rate, respiratory rate, body temperature) Measure height, weight, body mass index, and waist circumference Grip test Fasting blood tests Pregnancy test (if applicable) Fibroscan with CAP score QOL questionnaire

Official Title
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A Feasibility Trial of One-carbon Metabolism Cofactor Supplements for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD)

Conditions
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NAFLD

Intervention / Treatment
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* Dietary Supplement: homocysteine (Hcy) lowering supplements


Participation Criteria
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Eligibility Criteria
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We will enroll NAFLD patients, blocked by age 50 years (≤ 50; > 50) and sex (M; F, four patients/subjects in each block). Inclusion Criteria for NAFLD Group: Increased hepatic fat accumulation diagnosed by either abdominal ultrasound or CT AND elevated CAP score of 280 dB/m or higher HOMA-IR ≥ 2 or the diagnosis of metabolic syndrome Chronic elevation of transaminases: ALT elevation (more than 2 times during the past 12 months, defined by 19 U/L for women and 30 U/L for men 31) Stable use of any potential anti-NASH therapy (i.e., vitamin E, pioglitazone, glucagon like peptide 1 agonist, etc.) for 6 months prior to screening. Aged 18+ years Able to provide legal consent Exclusion Criteria for NAFLD Group: Any contraindication to the study supplements Inability to obtain valid fibroscan measures at the screening Pregnancy or lactation Clinical diagnosis of cirrhosis or other chronic liver diseases Recent use of steatogenic medications Excess alcohol use (>21/ >14 drinks weekly in men/women) Chronic kidney disease Supplement use within 30 days, containing any of the study supplements Total parenteral nutrition Any clinical conditions associated with malabsorption Any active diagnosis of malignancy Use of immunosuppression

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAFLD Group<br>The NAFLD group will be asked to take Hcy lowering supplements (Vitamin B12, Folate, Vitamin B6, and Betaine) daily for 12 weeks. Over the course of approximately 12 to 13 weeks, participants will complete two in person visits and two phone visits. During the in person visits NAFLD participants will complete the following activities: Review medical history; Physical examination; Vital signs (blood pressure, heart rate, respiratory rate, body temperature); Measure height, weight, body mass index, and waist circumference; Grip test; Fasting blood tests; Pregnancy test (if applicable); Fibroscan with CAP score; QOL questionnaire | Dietary Supplement: homocysteine (Hcy) lowering supplements<br>* NAFLD participants will take homocysteine (Hcy) lowering supplements daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FibroScan-aspartate aminotransferase (FAST) score | To minimize interindividual variability of fibroscan measurements, all of the fibroscan will be performed by a single, experienced operator using the same probe (M vs. XL) and technique for the paired measurements. The FibroScan-aspartate aminotransferase (FAST) score is a simple algorithm that can diagnose NASH using an elevated (≥ 4) NAFLD activity score (NAS) and significant fibrosis score (≥ 2). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility as measured by percentage of completion of enrollment | The trial design will be considered feasible if at least 13 NAFLD patients (≥80%) are enrolled over the 4-month period | 4 months | 
| Assess safety of the trial. | Based on reported adverse reactions. | 12 weeks |