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Use of a Novel Drug in People With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD)

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ClinicalTrials.gov Identifier: NCT02605616
Recruitment Status : Recruiting
First Posted : November 16, 2015
Last Update Posted : November 9, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Rita Basu, Mayo Clinic

Brief Summary:
Does the novel drug decrease liver fat in subjects with NASH or NAFLD as compared to placebo

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease (NAFLD) Non-alcoholic Steatohepatitis (NASH) Drug: AZ compound Other: Placebo Phase 2

Detailed Description:
We propose to combine voxel matched magnetic resonance spectroscopy (MRS) and magnetic resonance elastography (MRE) liver (pre vs. post) to evaluate hepatic fat and hepatic fibrosis. We will also establish glucose tolerance status by our established labeled oral glucose tolerance test (OGTT) (6,6 ²H2 glucose). Following baseline evaluation subjects with biopsy/MRE proven NASH will be randomized to one of two groups and treated either with active drug (AZ compound) or placebo for 12 weeks (plus or minus 1 week). Subjects with history suggestive of non-alcoholic fatty liver disease (NAFLD) or NASH will be invited to participate. If they meet criteria following initial screening they will be included in the study. OGTT, liver MRS, MRE will be repeated. Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT),alkaline phosphatase (ALP)] as well as other safety tests [creatine phosphokinase (CPK), thyroid stimulating hormone (TSH), international normalized ratio (INR),total bilirubin] will be measured before, monthly during therapy and at one month following therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Double-Blinded, Placebo-controlled Phase IIa Study to Assess the Efficacy and Safety of a Novel AstraZeneca Compound in Subjects With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD)
Study Start Date : November 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Active drug AZ compound
AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Drug: AZ compound
AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Placebo Comparator: Placebo
Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Other: Placebo
Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).




Primary Outcome Measures :
  1. Change in Liver Fat Fraction (LFF) [ Time Frame: baseline, approximately 12 weeks ]

Secondary Outcome Measures :
  1. Change in Liver Enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) [ Time Frame: baseline, approximately 12 weeks ]
  2. Change in Liver Fibrosis [ Time Frame: baseline, approximately 12 weeks ]
    Liver fibrosis will be measured with Magnetic Resonance Enterography (MRE).

  3. Change in Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si liver) [ Time Frame: baseline, approximately 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 21-75
  • Body Mass Index (BMI) >19 kg/m^2
  • Subjects with biopsy/MRE proven NASH [MRS liver fat ≥ 5%, with elevated liver enzymes ALT <5x upper limit normal (ULN)].
  • Subjects with NAFLD and MRE shows F1 or greater fibrosis
  • Subjects with history suggestive of NAFLD/NASH
  • Total bilirubin must be < 1.5 x ULN and INR must be < 1.3 at baseline screening.
  • TSH and CPK will be within normal limits (WNL) at screening.
  • Subjects with type 2 diabetes who are on stable doses of medications (except pioglitazone) to control hyperglycemia and have baseline HbA1c of 10% or lower.
  • Hemoglobin must be greater than or equal to 12.0 in males and 11.0 in females.

Exclusion Criteria:

  • Medications that may affect glucose metabolism such as corticosteroids, opiates, barbiturates, and anticoagulants.
  • Subjects with anemia, and symptoms suggestive of undiagnosed illness, overt hepatic disease, stroke, Alzheimer's disease, autoimmune hepatitis, alcoholism or increased alcohol consumption over the American Diabetes Association (ADA) guidelines.
  • Any disorder that may potentially impact the outcome measures.
  • Pregnant women and children.
  • Subjects planning weight loss or in any weight loss program.
  • Subjects taking TZD's, Atazanavir, Indinavir, Ketoconazole, Valproic acid, Silybum marianum and Valeriana officinalis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02605616


Contacts
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Contact: Rita Basu, MD 434-982-5780 RBVD@hscmail.mcc.virginia.edu

Locations
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United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Pam Morris    434-924-5780    pm2t@hscmail.mcc.virginia.edu   
Sponsors and Collaborators
Mayo Clinic
AstraZeneca
Investigators
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Principal Investigator: Rita Basu, MD University of Virginia

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Responsible Party: Rita Basu, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02605616     History of Changes
Other Study ID Numbers: 15-000013
First Posted: November 16, 2015    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases