Non-Alcoholic Fatty Liver DiseaseNCT03073343
A Prospective, Randomized, Open Label Trial of Two Doses of Oral Betaine
A study testing Betaine (trimethyglycine) in people with Non-Alcoholic Fatty Liver Disease and Non Insulin Dependent Diabetes, run by Southern California Institute for Research and Education at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non Insulin Dependent Diabetes, ALT
- What is being tested?
- Betaine (trimethyglycine)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2013to 30 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years
- A clinical diagnosis of non-alcoholic fatty liver disease.
- Alanine aminotransferase (ALT) levels ≥60 IU/mL
- Laboratory tests as defined below:
- Platelets > 100,000/dL
- Total bilirubin < 2 mg/dL
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- 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
- 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
Who cannot join
- Evidence of liver disease other than non-alcoholic fatty liver disease or non-alcoholic steatohepatitis
- 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
- Active substance abuse within the past year
- Prior or ongoing use of injectable insulin
- Use of oral corticosteroids within the prior 30 days
- Hospitalization within the past 14 days
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- Known HIV infection
- HgA1c >10%
- Known heart failure of New York Heart Association class 2, 3, or 4
- Any condition, which in the opinion of the investigator, would impede compliance or hinder the completion of the study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to betaine
- Current use of betaine or S-adenosylmethionine supplements, or refusal to abstain from their use during the study
- Known cystathionine beta-synthase (CBS) deficiency.
- Pregnancy or refusal to use birth control measures or breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
VA Long Beach Healthcare System
Long Beach, California, 90822
Aliya Asghar, MPH, 562-826-5212, aliya.asghar@va.gov
Timothy R Morgan, MD, 562-826-5212, timothy.morgan@va.gov
About this study
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)
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.
Read the detailed 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.
- Being tested
- Betaine (trimethyglycine)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Betaine (trimethyglycine)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.
| Study group | Role | What they receive |
|---|---|---|
| diabetic patients with NAFLD | Active comparator | 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. Receives: Dietary Supplement: Betaine (trimethyglycine) |
| non-diabetics with NAFLD | Active comparator | 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. Receives: Dietary Supplement: Betaine (trimethyglycine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: after 12 weeks of Betaine
Secondary outcomes (1)
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)
Measured: after 12 weeks of Betaine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2017
- Study start12 Nov 2013
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southern California Institute for Research and Education
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Timothy Morgan, MD, Southern California Institute for Research and Education
- Investigators
- Timothy R Morgan, MD, Principal investigator, VA Long Beach Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03073343
- Sponsor's protocol ID
- Betaine 2
- Status last verified
- May 2024
- First submitted
- 20 Feb 2017
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared with anyone outside authorized research personnel.
Publications
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.
PubMed 10348825Caldwell 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.
PubMed 10051466
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03073343
- Acronym / sponsor ID
- Betaine 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Southern California Institute for Research and EducationUniversity, hospital or other
- Study start
- 12 Nov 2013 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 8 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| diabetic patients with NAFLD | Active comparator | Dietary Supplement: Betaine (trimethyglycine)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. |
| non-diabetics with NAFLD | Active comparator | Dietary Supplement: Betaine (trimethyglycine)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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age 18-75 years
- A clinical diagnosis of non-alcoholic fatty liver disease.
- Alanine aminotransferase (ALT) levels ≥60 IU/mL
- Laboratory tests as defined below:
- Fasting blood sugar ≥ 126mg/dL
Key exclusion criteria (14 listed)
- Evidence of liver disease other than non-alcoholic fatty liver disease or non-alcoholic steatohepatitis
- 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
- Active substance abuse within the past year
- Prior or ongoing use of injectable insulin
- Use of oral corticosteroids within the prior 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | diabetic patients with NAFLD, non-diabetics with NAFLD |
Primary outcome
Change in alanine aminotransferase (ALT) level in all study participants
Time frame: after 12 weeks of Betaine
Compare the week 12 ALT levels with the baseline ALT in study patients. Comparison will be performed using a paired t-test.
1 secondary outcome
Compare changes in alanine aminotransferase (ALT) level in both cohorts
Time frame: after 12 weeks of Betaine
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Background: PubMed 10348825Matteoni 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.
- Background: PubMed 10051466Caldwell 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.
- Individual participant dataSharing planned: No. IPD will not be shared with anyone outside authorized research personnel.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy R Morgan, MD principal investigator
VA Long Beach Healthcare System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Betaine (trimethyglycine) in people with Non-Alcoholic Fatty Liver Disease and Non Insulin Dependent Diabetes, run by Southern California Institute for Research and Education at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Timothy R Morgan, MD (562-826-5212, timothy.morgan@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in alanine aminotransferase (ALT) level in all study participants (time frame: after 12 weeks of Betaine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03073343, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.