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

NCT ID: NCT03073343

Last Updated: 2024-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-12

Study Completion Date

2025-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Alcoholic Fatty Liver Disease Non Insulin Dependent Diabetes ALT

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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diabetic patients with NAFLD

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 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.

Group Type ACTIVE_COMPARATOR

Betaine (trimethyglycine)

Intervention Type DIETARY_SUPPLEMENT

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.

non-diabetics with NAFLD

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 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.

Group Type ACTIVE_COMPARATOR

Betaine (trimethyglycine)

Intervention Type DIETARY_SUPPLEMENT

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.

Interventions

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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.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

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


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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Southern California Institute for Research and Education

OTHER

Sponsor Role lead

Responsible Party

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Timothy Morgan, MD

Chief, Hepatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Timothy R Morgan, MD

Role: PRINCIPAL_INVESTIGATOR

VA Long Beach Healthcare System

Locations

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VA Long Beach Healthcare System

Long Beach, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Timothy R Morgan, MD

Role: CONTACT

562-826-5212

Aliya Asghar, MPH

Role: CONTACT

562-826-5212

Facility Contacts

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Aliya Asghar, MPH

Role: primary

562-826-5212

Timothy R Morgan, MD

Role: backup

562-826-5212

References

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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.

Reference Type BACKGROUND
PMID: 10348825 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10051466 (View on PubMed)

Other Identifiers

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Betaine 2

Identifier Type: -

Identifier Source: org_study_id

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