Non-alcoholic Fatty Liver Disease (NAFLD)Phase 1NCT02457286
Improving Insulin Resistance To Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study
A Phase 1 study testing Metformin, Lifestyle modifications and Fibroscan device (Echosens) in people with Non-alcoholic Fatty Liver Disease (NAFLD), run by Northwell Health at 1 site in United States.
Trial summary
Metformin is being compared to exercise and diet modifications. The researchers are interested in learning if the addition of metformin to lifestyle modifications is more helpful in treating the condition or disorder. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- Metformin, Lifestyle modifications and Fibroscan device (Echosens)
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Jul 2017
- Phase
- Phase 1
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- subjects between ages 18-80
- diagnosed with NAFLD by alanine aminotransferase
- (ALT) levels >1.5x the upper limit of normal with an otherwise nondiagnostic hepatic serology workup, ultrasound evidence, and/or histologically confirmed NAFLD within the past 1 year.
- The upper limit of normal for ALT will be defined as 35 U/L in males and 19 U/L in females
Who cannot join
- A prior history of diabetes
- Failure to meet criteria for HbA1C screening
- Evidence of hepatic disorders
- Use of insulin or oral hypoglycemic agents
- eGFR <30
- Blood transfusion within past 3 months
Show all 13Show fewer
- Steroid use in the past 6 months
- Excessive alcohol use (more than 20g per day in women and more than 30g per day in men)
- Acute or unstable congestive heart failure
- Age >80 years old
- Lactic acidosis
- Inability to consent due to cognitive impairment.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improving Insulin Resistance to Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study
Metformin is being compared to exercise and diet modifications. The researchers are interested in learning if the addition of metformin to lifestyle modifications is more helpful in treating the condition or disorder. Although metformin is FDA approved to treat type 2 diabetes, it is not FDA approved for the treatment of Non-alcoholic fatty liver (NAFLD) and is considered investigational for the purpose of this study.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and a common cause of unexplained mildly elevated serum aminotransferase levels. NAFLD, initially felt to be benign, is now known to potentially progress to cirrhosis and its complications, including the development of liver cancer. NAFLD is strongly correlated with Type 2 Diabetes, insulin resistance, and the metabolic syndrome (1-6). It is hypothesized that the pathogenesis of hepatic injury in NAFLD is due to insulin resistance and the oxidative stress associated with obesity and metabolic syndrome (7). No adequate medical treatment has been shown to be effective for the treatment of NAFLD. Several studies (8-22) have evaluated the effect of metformin in patients with NAFLD in relation to insulin resistance, Homeostatic Model Assessment Insulin Resistance Index (HOMA-IR) values, aminotransferase levels, liver morphology, and histological improvement with treatment. These studies however have shown discrepant results with relation to aminotransferase levels and only a few studies have been able to evaluate histological improvement with follow-up biopsies. There have been no studies focusing specifically on the pre-diabetic population. These patients who are at an increased risk of progressing to diabetes may exhibit a different response to treatment with metformin than non-diabetic or diabetic patients. All the studies support the fact that metformin has a beneficial effect on improving insulin resistance and decreasing the incidence of metabolic syndrome, but there is no consensus thus far on its influence on NAFLD. The majority of published studies were limited by small sample size. Randomized controlled trials with adequate sample size and of longer duration are needed as well as studies assessing endpoints such as liver morphology and histology. The results of this pilot study are significant in that metformin may be a relatively safe and inexpensive way, in addition to lifestyle modifications, to treat NAFLD. The results of this pilot study will pave the way for the larger power, longer duration study required to answer this question.
- Being tested
- Metformin, Lifestyle modifications, Fibroscan device (Echosens)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Although metformin is FDA approved to treat type 2 diabetes, it is not FDA approved for the treatment of NAFLD and is considered investigational for the purpose of this study.
Lifestyle modificationsBehavioural
Recommendations for lifestyle modification will be based on the Diabetes Prevention Program 2002 (26) and will include recommendations for greater than 150 minutes of physical activity weekly, referrals to group and/or individualized sessions with nutritionists and/or lifestyle coaches as well as educational materials
Fibroscan device (Echosens)Device
This study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin is being compared to exercise and diet modifications. The study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity. In this technique, a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe Receives: Drug: Metformin; Behavioral: Lifestyle modifications; Device: Fibroscan device (Echosens) |
| Lifestyle modification | Experimental | The researchers are interested in learning if the addition of metformin to lifestyle modifications is more helpful in treating participants condition or disorder. The study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity. In this technique, a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe Receives: Behavioral: Lifestyle modifications; Device: Fibroscan device (Echosens) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in NAFLD as measured by ALT levels
The primary endpoint variable is the improvement in NAFLD after 12 months of treatment, as measured by the change in ALT levels from baseline to the end of a one year follow-up. A decrease of at least 25% from baseline will be considered a clinically relevant response.
Measured: 12 Months
Secondary outcomes (2)
Incidence of metabolic syndrome (insulin resistance)
The study will be using measurements of BMI, waist circumference, blood pressure, lipids and fasting blood glucose levels to assess insulin resistance.
Measured: 12 months
Incidence of NAFLD fibrosis scores after 12 months of treatment as measured by Fibroscan
A NAFLD Fibrosis Score (28), a noninvasive scoring system for liver fibrosis in patients with NAFLD, can be calculated and potentially used to assess for histologic improvement with metformin, which thus far has never been assessed.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startJun 2015
- Primary completionJul 2017
- Study completionJul 2017
Why it stopped: patients do not want to participate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Bernstein, Northwell Health
- Investigators
- David Bernstein, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457286
- Sponsor's protocol ID
- IRB# 13-204
- Status last verified
- Jul 2016
- First submitted
- 14 May 2015
- Last updated
- 28 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Ortiz-Lopez C, Lomonaco R, Orsak B, Finch J, Chang Z, Kochunov VG, Hardies J, Cusi K. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care. 2012 Apr;35(4):873-8. doi: 10.2337/dc11-1849. Epub 2012 Feb 28.
PubMed 22374640Arase Y, Suzuki F, Ikeda K, Kumada H, Tsuji H, Kobayashi T. Multivariate analysis of risk factors for the development of type 2 diabetes in nonalcoholic fatty liver disease. J Gastroenterol. 2009;44(10):1064-70. doi: 10.1007/s00535-009-0091-1. Epub 2009 Jun 17.
PubMed 19533014Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005 Jul;42(1):44-52. doi: 10.1002/hep.20734.
PubMed 15895401Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol. 2009 Apr;104(4):861-7. doi: 10.1038/ajg.2009.67. Epub 2009 Mar 17.
PubMed 19293782Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol. 2009 Jun;46(2):113-8. doi: 10.1007/s00592-008-0067-2. Epub 2008 Oct 7.
PubMed 18839053Lidofsky SD. Nonalcoholic fatty liver disease: diagnosis and relation to metabolic syndrome and approach to treatment. Curr Diab Rep. 2008 Feb;8(1):25-30. doi: 10.1007/s11892-008-0006-1.
PubMed 18366995
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Insulin Resistance to Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study
- ClinicalTrials.gov ID
- NCT02457286
- Acronym / sponsor ID
- IRB# 13-204
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: patients do not want to participate
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 29 May 2015 (estimated)
- 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.
Metformin is being compared to exercise and diet modifications. The researchers are interested in learning if the addition of metformin to lifestyle modifications is more helpful in treating the condition or disorder. Although metformin is FDA approved to treat type 2 diabetes, it is not FDA approved for the treatment of Non-alcoholic fatty liver (NAFLD) and is considered investigational for the purpose of this study.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and a common cause of unexplained mildly elevated serum aminotransferase levels. NAFLD, initially felt to be benign, is now known to potentially progress to cirrhosis and its complications, including the development of liver cancer. NAFLD is strongly correlated with Type 2 Diabetes, insulin resistance, and the metabolic syndrome (1-6). It is hypothesized that the pathogenesis of hepatic injury in NAFLD is due to insulin resistance and the oxidative stress associated with obesity and metabolic syndrome (7). No adequate medical treatment has been shown to be effective for the treatment of NAFLD. Several studies (8-22) have evaluated the effect of metformin in patients with NAFLD in relation to insulin resistance, Homeostatic Model Assessment Insulin Resistance Index (HOMA-IR) values, aminotransferase levels, liver morphology, and histological improvement with treatment. These studies however have shown discrepant results with relation to aminotransferase levels and only a few studies have been able to evaluate histological improvement with follow-up biopsies. There have been no studies focusing specifically on the pre-diabetic population. These patients who are at an increased risk of progressing to diabetes may exhibit a different response to treatment with metformin than non-diabetic or diabetic patients. All the studies support the fact that metformin has a beneficial effect on improving insulin resistance and decreasing the incidence of metabolic syndrome, but there is no consensus thus far on its influence on NAFLD. The majority of published studies were limited by small sample size. Randomized controlled trials with adequate sample size and of longer duration are needed as well as studies assessing endpoints such as liver morphology and histology. The results of this pilot study are significant in that metformin may be a relatively safe and inexpensive way, in addition to lifestyle modifications, to treat NAFLD. The results of this pilot study will pave the way for the larger power, longer duration study required to answer this question.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin, Behavioral: Lifestyle modifications, Device: Fibroscan device (Echosens)Metformin is being compared to exercise and diet modifications. The study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity. In this technique, a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe |
| Lifestyle modification | Experimental | Behavioral: Lifestyle modifications, Device: Fibroscan device (Echosens)The researchers are interested in learning if the addition of metformin to lifestyle modifications is more helpful in treating participants condition or disorder. The study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity. In this technique, a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- subjects between ages 18-80
- diagnosed with NAFLD by alanine aminotransferase
- (ALT) levels >1.5x the upper limit of normal with an otherwise nondiagnostic hepatic serology workup, ultrasound evidence, and/or histologically confirmed NAFLD within the past 1 year.
- The upper limit of normal for ALT will be defined as 35 U/L in males and 19 U/L in females
Key exclusion criteria (13 listed)
- A prior history of diabetes
- Failure to meet criteria for HbA1C screening
- Evidence of hepatic disorders
- Use of insulin or oral hypoglycemic agents
- eGFR <30
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 |
|---|---|---|
| MetforminAlso: GlucophageAlthough metformin is FDA approved to treat type 2 diabetes, it is not FDA approved for the treatment of NAFLD and is considered investigational for the purpose of this study. | Drug | Metformin |
| Lifestyle modificationsRecommendations for lifestyle modification will be based on the Diabetes Prevention Program 2002 (26) and will include recommendations for greater than 150 minutes of physical activity weekly, referrals to group and/or individualized sessions with nutritionists and/or lifestyle coaches as well as educational materials | Behavioural | Lifestyle modification, Metformin |
| Fibroscan device (Echosens)This study will be incorporating the use of a Fibroscan device (Echosens) at the initial visit and upon completion of the study, which works by measuring shear wave velocity. | Device | Lifestyle modification, Metformin |
Primary outcome
Improvement in NAFLD as measured by ALT levels
Time frame: 12 Months
The primary endpoint variable is the improvement in NAFLD after 12 months of treatment, as measured by the change in ALT levels from baseline to the end of a one year follow-up. A decrease of at least 25% from baseline will be considered a clinically relevant response.
2 secondary outcomes
Incidence of metabolic syndrome (insulin resistance)
Time frame: 12 months
Incidence of NAFLD fibrosis scores after 12 months of treatment as measured by Fibroscan
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Results publication: PubMed 22374640Ortiz-Lopez C, Lomonaco R, Orsak B, Finch J, Chang Z, Kochunov VG, Hardies J, Cusi K. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care. 2012 Apr;35(4):873-8. doi: 10.2337/dc11-1849. Epub 2012 Feb 28.
- Results publication: PubMed 19533014Arase Y, Suzuki F, Ikeda K, Kumada H, Tsuji H, Kobayashi T. Multivariate analysis of risk factors for the development of type 2 diabetes in nonalcoholic fatty liver disease. J Gastroenterol. 2009;44(10):1064-70. doi: 10.1007/s00535-009-0091-1. Epub 2009 Jun 17.
- Results publication: PubMed 15895401Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005 Jul;42(1):44-52. doi: 10.1002/hep.20734.
- Results publication: PubMed 19293782Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol. 2009 Apr;104(4):861-7. doi: 10.1038/ajg.2009.67. Epub 2009 Mar 17.
- Results publication: PubMed 18839053Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol. 2009 Jun;46(2):113-8. doi: 10.1007/s00592-008-0067-2. Epub 2008 Oct 7.
- Results publication: PubMed 18366995Lidofsky SD. Nonalcoholic fatty liver disease: diagnosis and relation to metabolic syndrome and approach to treatment. Curr Diab Rep. 2008 Feb;8(1):25-30. doi: 10.1007/s11892-008-0006-1.
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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.
David Bernstein, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin, Lifestyle modifications and Fibroscan device (Echosens) in people with Non-alcoholic Fatty Liver Disease (NAFLD), run by Northwell Health 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 4 inclusion and 13 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: withdrawn, as of the sponsor's last update on 28 Jul 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in NAFLD as measured by ALT levels (time frame: 12 Months). 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 NCT02457286, which also lists 6 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 28 Jul 2017.