A Feasibility Trial of OCM Supplements for the Treatment of NAFLD

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

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.

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Dietary supplement: homocysteine (Hcy) lowering supplements

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Increased hepatic fat accumulation diagnosed by either abdominal ultrasound or CT AND elevated CAP score of 280 dB/m or higher
2. HOMA-IR ≥ 2 or the diagnosis of metabolic syndrome
3. 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)
4. 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.
5. Aged 18+ years
6. Able to provide legal consent

Exclusion Criteria for NAFLD Group:

1. Any contraindication to the study supplements
2. Inability to obtain valid fibroscan measures at the screening
3. Pregnancy or lactation
4. Clinical diagnosis of cirrhosis or other chronic liver diseases
5. Recent use of steatogenic medications
6. Excess alcohol use (>21/ >14 drinks weekly in men/women)
7. Chronic kidney disease
8. Supplement use within 30 days, containing any of the study supplements
9. Total parenteral nutrition
10. Any clinical conditions associated with malabsorption
11. Any active diagnosis of malignancy
12. Use of immunosuppression

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NAFLD Group; 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; NAFLD participants will take homocysteine (Hcy) lowering supplements daily for 12 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Ayako Suzuki, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Actual): August 23, 2024
• Study Completion (Actual): August 23, 2024

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: Pro00112107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not intend to share IDP with other researchers at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No