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Nonalcoholic Fatty Liver Disease (NAFLD)Phase 2FLINTNCT01265498

The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in NASH Treatment Trial(FLINT)

A Phase 2 study testing obeticholic acid in people with Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Administration of the farnesoid X receptor (FXR) ligand obeticholic acid (OCA) for 72 weeks to subjects with biopsy evidence of nonalcoholic steatohepatitis (NASH) will result in improvement in their liver disease as measured by changes in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
obeticholic acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
283 participants
Where
9 sitesUnited States
Study dates
Mar 2011to Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older as of the initial screening interview and provision of consent
  • Histologic evidence of definite or probable nonalcoholic steatohepatitis (NASH) based upon a liver biopsy obtained no more than 90 days prior to randomization and a nonalcoholic fatty liver disease activity score (NAS) of 4 or greater with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).

Who cannot join

  • Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males, on average)
  • Inability to reliably quantify alcohol consumption based upon local study physician judgment
  • Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the year prior to randomization
  • Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass)
  • Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher within 60 days prior to enrollment
  • Presence of cirrhosis on liver biopsy
Show all 37Show fewer
  • A platelet count below 100,000/mm3
  • Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
  • Serum albumin less than 3.2 grams/deciliter (g/dL)
  • International Normalized Ratio(INR)greater than 1.3
  • Direct bilirubin greater than 1.3 milligrams per deciliter (mg/dL)
  • History of esophageal varices, ascites or hepatic encephalopathy
  • Evidence of other forms of chronic liver disease:
  • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
  • Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid (RNA) or positive hepatitis C antibody (anti-HCV)
  • Evidence of ongoing autoimmune liver disease as defined by compatible liver histology
  • Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii)Presence of anti-mitochondrial antibody (AMA) (iii)Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts
  • Primary sclerosing cholangitis
  • Wilson's disease as defined by ceruloplasmin below the limits of normal and compatible liver histology
  • Alpha-1-antitrypsin(A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by alpha-1 antitrypsin level less than normal; exclusion at the discretion of the study physician)
  • History of hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy
  • Drug-induced liver disease as defined on the basis of typical exposure and history
  • Known bile duct obstruction
  • Suspected or proven liver cancer
  • Any other type of liver disease other than nonalcoholic steatohepatitis (NASH)
  • Serum alanine aminotransferase (ALT) greater than 300 units per liter (U/L)
  • Serum creatinine of 2.0 mg/dL or greater
  • Use of ursodeoxycholic acid (Ursodiol, Urso) within 90 days prior to enrollment
  • Inability to safely obtain a liver biopsy
  • History of biliary diversion
  • Known positivity for Human Immunodeficiency Virus (HIV) infection
  • Active, serious medical disease with likely life expectancy less than 5 years
  • Active substance abuse including inhaled or injection drugs in the year prior to screening
  • Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding
  • Participation in an investigational new drug (IND) trial in the 30 days before randomization
  • Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study
  • Failure to give informed consent

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Case Western Reserve University

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Indiana University

    Indianapolis, Indiana, 46202

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of California, San Diego

    San Diego, California, 92103

  • University of California, San Francisco

    San Francisco, California, 94143

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • St. Louis University

    St Louis, Missouri, 63104

Other trials in United States

About this study

Official title: The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis (NASH) Treatment (FLINT) Trial

Administration of the farnesoid X receptor (FXR) ligand obeticholic acid (OCA) for 72 weeks to subjects with biopsy evidence of nonalcoholic steatohepatitis (NASH) will result in improvement in their liver disease as measured by changes in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS).

Read the detailed description

To evaluate whether treatment with obeticholic acid, 25 mg daily for 72 weeks compared to treatment with placebo, improves the severity of nonalcoholic fatty liver disease (NAFLD) as determined from hepatic histology.

Being tested
obeticholic acid, placebo
Keywords
Farnesoid X Receptor, FXR, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, NAFLD, NASH, obeticholic acid
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.

  • obeticholic acidDrug

    Also called farnesoid X receptor (FXR) ligand obeticholic acid (OCA)

    25 mg daily for 72 weeks

  • placeboDrug

    Also called Placebo for obeticholic acid

    placebo capsule, 25 mg daily for 72 weeks

Study groups in NCT01265498
Study groupRoleWhat they receive
Obeticholic acidActive comparatorobeticholic acid
Receives: Drug: obeticholic acid
PlaceboPlacebo comparatorPlacebo
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

    Centrally scored histological improvement in nonalcoholic fatty liver disease (NAFLD) from baseline to the end of 72 weeks of treatment, where improvement is defined as:

    1. No worsening in fibrosis; and
    2. A decrease in NAFLD Activity Score (NAS) of at least 2 points

    Measured: baseline to 72 weeks

Secondary outcomes (47)

  1. Resolution of NASH Diagnosis

    Resolution of definite nonalcoholic steatohepatitis. Resolution defined as either not NAFLD, or NAFLD but not non-alcoholic steatohepatitis on week 72 biopsy

    Measured: baseline to 72 weeks

  2. Fibrosis: Patient With Improvement

    Patients with improvement in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis.

    Measured: baseline to 72 weeks

  3. Fibrosis: Change in Score

    Change in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis.

    Measured: baseline to 72 weeks

  4. Total NAFLD Activity Score: Change in Score

    NAFLD activity score was assessed on a scale of 0-8, with higher scores showing more severe disease (the components of this measure are steatosis [assessed on a scale of 0-3], lobular inflammation [assessed on a scale of 0-3], and hepatocellular ballooning [assessed on a scale of 0-2]).

    Measured: baseline to 72 weeks

  5. Hepatocellular Ballooning: Patients With Improvement

    Patients with improvement in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning.

    Measured: baseline to 72 weeks

  6. Hepatocellular Ballooning: Change in Score

    Change in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning.

    Measured: baseline to 72 weeks

  7. Steatosis: Patients With Improvement

    Patients with improvement in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.

    Measured: baseline to 72 weeks

  8. Steatosis: Change in Score

    Change in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.

    Measured: baseline to 72 weeks

  9. Lobular Inflammation: Patients With Improvement

    Patients with improvement in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation.

    Measured: baseline to 72 weeks

  10. Lobular Inflammation: Change in Score

    Change in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation.

    Measured: baseline to 72 weeks

  11. Portal Inflammation: Patients With Improvement

    Patients with improvement in portal inflammation score. Portal inflammation was assessed on a scale of 0-2, with higher scores showing more severe portal inflammation.

    Measured: baseline to 72 weeks

  12. Portal Inflammation: Change in Score

    Change in portal inflammation score. Portal inflammation was assessed on a scale of 0-3, with higher scores showing more severe portal inflammation.

    Measured: baseline to 72 weeks

  13. Change in Alanine Aminotransferase

    Measured: baseline to 72 weeks

  14. Change in Asparate Aminotransferase

    Measured: baseline to 72 weeks

  15. Change in Alkaline Phosphatase

    Measured: baseline to 72 weeks

  16. Change in γ-glutamyl Transpeptidase

    Measured: baseline to 72 weeks

  17. Change in Total Bilirubin

    Measured: baseline to 72 weeks

  18. Change in Total Cholesterol

    Measured: baseline to 72 weeks

  19. Change in HDL Cholesterol

    Measured: baseline to 72 weeks

  20. Change in LDL Cholesterol

    Measured: baseline to 72 weeks

  21. Change in Triglycerides

    Measured: baseline to 72 weeks

  22. Change in Haemoglobin

    Measured: baseline to 72 weeks

  23. Change in Haematocrit

    Measured: baseline to 72 weeks

  24. Change in Mean Corpuscular Volume

    Measured: baseline to 72 weeks

  25. Change in White Blood Cell Count

    Measured: baseline to 72 weeks

  26. Change in Platelet Count

    Measured: baseline to 72 weeks

  27. Change in Bicarbonate

    Measured: baseline to 72 weeks

  28. Change in Calcium

    Measured: baseline to 72 weeks

  29. Change in Phosphate

    Measured: baseline to 72 weeks

  30. Change in Creatinine

    Measured: baseline to 72 weeks

  31. Change in Uric Acid

    Measured: baseline to 72 weeks

  32. Change in Albumin

    Measured: baseline to 72 weeks

  33. Change in Total Protein

    Measured: baseline to 72 weeks

  34. Change in Prothrombin Time

    Measured: baseline to 72 weeks

  35. Change in International Normalised Ratio

    Measured: baseline to 72 weeks

  36. Change in Fasting Serum Glucose

    Measured: baseline to 72 weeks

  37. Change in Insulin

    Measured: baseline to 72 weeks

  38. Change in HOMA-IR

    Measured: baseline to 72 weeks

  39. Change in Glycated Haemoglobin A1c

    Measured: baseline to 72 weeks

  40. Change in Weight

    Measured: baseline to 72 weeks

  41. Change in Body-mass Index

    Measured: baseline to 72 weeks

  42. Change in Waist Circumference

    Measured: baseline to 72 weeks

  43. Change in Waist-to-hip Ratio

    Measured: baseline to 72 weeks

  44. Change in Systolic Blood Pressure

    Measured: baseline to 72 weeks

  45. Change in Diastolic Blood Pressure

    Measured: baseline to 72 weeks

  46. Change in SF-36 Quality of Life Physical Component Summary

    Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome.

    Measured: baseline to 72 weeks

  47. Change in SF-36 Quality of Life Mental Component Summary

    Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome.

    Measured: baseline to 72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2010 (estimated)
  2. Study startMar 2011
  3. Primary completionJan 2014
  4. Study completionSep 2014

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
283 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01265498
Sponsor's protocol ID
NASH-FLINT (IND)
Other IDs
U01DK061730
Acronym
FLINT
Status last verified
Jul 2015
First submitted
21 Dec 2010
Last updated
6 Apr 2018
Data monitoring committee
Yes

Publications

  • Hakim A, Lin KH, Schwantes-An TH, Abreu M, Tan J, Guo X, Yates KP, Lotta L, Verweij N, Loomba R, Kleiner DE, Schwimmer JB, Rotter JI, Chalasani NP. A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework. Hepatol Commun. 2025 May 29;9(6):e0728. doi: 10.1097/HC9.0000000000000728. eCollection 2025 Jun 1.

    PubMed 40434633

  • Shen W, Middleton MS, Cunha GM, Delgado TI, Wolfson T, Gamst A, Fowler KJ, Alazraki A, Trout AT, Ohliger MA, Shah SN, Bashir MR, Kleiner DE, Loomba R, Neuschwander-Tetri BA, Sanyal AJ, Zhou J, Sirlin CB, Lavine JE. Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis. J Hepatol. 2023 Feb;78(2):238-246. doi: 10.1016/j.jhep.2022.10.027. Epub 2022 Nov 8.

    PubMed 36368598

  • Vilar-Gomez E, Gawrieh S, Liang T, McIntyre AD, Hegele RA, Chalasani N. Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD. J Clin Lipidol. 2021 Mar-Apr;15(2):275-291. doi: 10.1016/j.jacl.2020.12.010. Epub 2020 Dec 27.

    PubMed 33454241

  • Loomba R, Neuschwander-Tetri BA, Sanyal A, Chalasani N, Diehl AM, Terrault N, Kowdley K, Dasarathy S, Kleiner D, Behling C, Lavine J, Van Natta M, Middleton M, Tonascia J, Sirlin C; NASH Clinical Research Network. Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH. Hepatology. 2020 Oct;72(4):1219-1229. doi: 10.1002/hep.31121. Epub 2020 Oct 9.

    PubMed 31965579

  • Siddiqui MS, Van Natta ML, Connelly MA, Vuppalanchi R, Neuschwander-Tetri BA, Tonascia J, Guy C, Loomba R, Dasarathy S, Wattacheril J, Chalasani N, Sanyal AJ; NASH CRN. Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis. J Hepatol. 2020 Jan;72(1):25-33. doi: 10.1016/j.jhep.2019.10.006. Epub 2019 Oct 18.

    PubMed 31634532

  • Chalasani N, Abdelmalek MF, Loomba R, Kowdley KV, McCullough AJ, Dasarathy S, Neuschwander-Tetri BA, Terrault N, Ferguson B, Shringarpure R, Shapiro D, Sanyal AJ. Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis. Liver Int. 2019 May;39(5):924-932. doi: 10.1111/liv.13974. Epub 2019 Feb 21.

    PubMed 30253043

  • Hameed B, Terrault NA, Gill RM, Loomba R, Chalasani N, Hoofnagle JH, Van Natta ML; NASH CRN. Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2018 Mar;47(5):645-656. doi: 10.1111/apt.14492. Epub 2018 Jan 14.

    PubMed 29333665

  • Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4. Epub 2014 Nov 7.

    PubMed 25468160

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing obeticholic acid in people with Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 9 sites 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 2 inclusion and 37 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: finished, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) (time frame: baseline to 72 weeks). 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 NCT01265498, which also lists 8 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 6 Apr 2018.

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