A Prospective, Randomized, Open Label Trial of Two Doses of Oral Betaine

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

A Prospective, Randomized, Open Label Trial of Two Doses of Oral Betaine in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) and Elevated Alanine Aminotransferase (ALT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03073343
• Other study ID #: Betaine 2
• Status: Recruiting
• Phase: N/A
• Start date: November 12, 2013
• Est. completion date: December 30, 2025

Study information

• Verified date: May 2024
• Source: Southern California Institute for Research and Education
• Contact: Timothy R Morgan, MD
• Phone: 562-826-5212
• Email: timothy.morgan[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Betaine (trimethyglycine) is a food supplement that is approved for sale in the United States without a prescription. In this study, betaine will be provided to patients as a powder that can be mixed with aqueous solutions and consumed orally.

Description:

This is a prospective, unblinded, randomized study of oral betaine in diabetic and non-diabetic patients who have a clinical diagnosis of NAFLD and an ALT≥ 50 IU/mL. A clinical diagnosis of NAFLD is based on the presence of risk factors for NAFLD (such as overweight and insulin resistance) and the exclusion of other causes of liver disease, such as alcohol or viral hepatitis.

Two cohorts of patients will be studied: Cohort 1 (diabetic) will consist of patients with a clinical diagnosis of non-insulin dependent type II diabetes mellitus; Cohort 2 (non-diabetics) will consist of patients without a clinical diagnosis of type 2 diabetes mellitus. 24 patients will be enrolled in each cohort (total of 48 patients enrolled in the study) with an anticipated drop out of 4 subjects per cohort.

Patients will be given dietary instructions and advice on exercise appropriate for the management of NAFLD (NIDDK and liverfoundation.org handouts). Patients will be prescribed 4 grams of betaine/day (2 grams PO BID) for the first 4 weeks of the study. After 4 weeks, patients in each cohort (NIDDM and non-diabetic) will be randomized (1:1) to continue receiving betaine 4 grams per day or increase to 8 grams per day for an additional 8 weeks. All patients will be seen in clinic on a monthly basis during treatment, and again 4 and 12 weeks after completion of betaine treatment. The total duration of the study is 24 weeks (12 weeks of betaine treatment and 12 weeks of follow-up).

The primary outcome is change in ALT during 12 weeks of betaine treatment (i.e., ALT at week 12 compared with ALT at baseline (entry). Secondary outcomes include safety, efficacy of betaine in each cohort, and are changes in laboratory tests related to NAFLD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Inclusion Criteria for all patients:

1. Age 18-75 years

2. A clinical diagnosis of non-alcoholic fatty liver disease.

3. Alanine aminotransferase (ALT) levels =60 IU/mL

4. Laboratory tests as defined below:

• Platelets > 100,000/dL

• Total bilirubin < 2 mg/dL

• Creatinine < 1.6 mg/dL

• Inclusion Criteria for Group 1: diabetic patients

1. At least one of the following:

• Fasting blood sugar = 126mg/dL

• Hemoglobin A1c (HgA1c) of > 6.5%

• 2-hour plasma glucose level of > 200mg/dL during a glucose tolerance test

• Receiving treatment with insulin sensitizing drugs (metformin) or sulfonylureas (glipizide, etc.) 3. Inclusion Criteria for Group 2: Non-diabetic patients with insulin resistance (must have both)

• Fasting blood glucose of 100-125 mg/dL and

• Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score >3.0

Exclusion Criteria:

1. Evidence of liver disease other than non-alcoholic fatty liver disease or non-alcoholic steatohepatitis

2. Alcohol consumption of more than 12g/d (1 drink) for females or more than 24g/day (2 drinks) for males, for 3 months during the past year

3. Active substance abuse within the past year

4. Prior or ongoing use of injectable insulin

5. Use of oral corticosteroids within the prior 30 days

6. Hospitalization within the past 14 days

7. Known HIV infection

8. HgA1c >10%

9. Known heart failure of New York Heart Association class 2, 3, or 4

10. Any condition, which in the opinion of the investigator, would impede compliance or hinder the completion of the study

11. History of allergic reactions attributed to compounds of similar chemical or biologic composition to betaine

12. Current use of betaine or S-adenosylmethionine supplements, or refusal to abstain from their use during the study

13. Known cystathionine beta-synthase (CBS) deficiency.

14. Pregnancy or refusal to use birth control measures or breast feeding

Related Conditions & MeSH terms

• ALT
• Diabetes Mellitus, Type 2
• Fatty Liver
• Liver Diseases
• Non Insulin Dependent Diabetes
• Non-Alcoholic Fatty Liver Disease

Intervention

Dietary Supplement:
• Betaine (trimethyglycine)
Betaine (trimethyglycine) is a food supplement that is approved for sale in the United States without a prescription. In this study, betaine will be provided to patients as a powder that can be mixed with aqueous solutions and consumed orally.

Locations

Country	Name	City	State
United States	VA Long Beach Healthcare System	Long Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Southern California Institute for Research and Education

Country where clinical trial is conducted

United States, 

References & Publications (2)

Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999 Mar;29(3):664-9. doi: 10.1002/hep.510290347. — View Citation

Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999 Jun;116(6):1413-9. doi: 10.1016/s0016-5085(99)70506-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in alanine aminotransferase (ALT) level in all study participants	Compare the week 12 ALT levels with the baseline ALT in study patients. Comparison will be performed using a paired t-test.	after 12 weeks of Betaine
Secondary	Compare changes in alanine aminotransferase (ALT) level in both cohorts	A Paired T test analysis will compare changes in ALT levels between Patients with NIDDM (cohort 1) and Patients without NIDDM (cohort 2)	after 12 weeks of Betaine