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

Primary Purpose

Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH)

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

AZ compound

Placebo

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease (NAFLD)

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: 21-75
Body Mass Index (BMI) >19 kg/m^2
Subjects with biopsy/MRE proven NASH [MRE liver fat ≥ 5%, with elevated liver enzymes ALT <5x upper limit normal (ULN)].
Subjects with NAFLD and MRE shows F0 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.

Sites / Locations

Yogesh Yadav

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active drug AZ compound

Placebo

Arm Description

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

Outcomes

Primary Outcome Measures

Percentage Change in Hepatic Fat

Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of <5% is used to distinguish between normal and fatty liver.

Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol

Hepatic conversion of [13C] cortisone to [13C] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test.

Secondary Outcome Measures

Liver Fibrosis Measured With MRE in kPa

Liver fibrosis will be measured with Magnetic Resonance Enterography (MRE) at baseline and then compared after ~12 weeks of treatment. A clinical cut-off of 2.93 kPa was used to classify the results as either normal or elevated liver stiffness. Change in Liver fibrosis (kPa) is compared in between the groups.

Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver)

Total insulin sensitivity (Si) and hepatic insulin sensitivity (Si liver) will be measured with an Oral glucose Tolerance test at baseline and after ~12 weeks of treatment.

Full Information

NCT ID

NCT02605616

First Posted

September 18, 2015

Last Updated

March 10, 2022

Sponsor

University of Virginia

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02605616

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Terminated

Why Stopped

Astra Zeneca notified Dr. Rita Basu that they will not manufacture new drug due to business reasons and study was stopped.

Study Start Date

November 2015 (undefined)

Primary Completion Date

September 2019 (Actual)

Study Completion Date

September 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Virginia

Collaborators

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed Description

We propose to evaluate hepatic fat and hepatic fibrosis using magnetic resonance elastography (MRE) liver (pre vs. post). 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 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. Furthermore, we will also do the subgroup analysis in NASH/NAFLD subjects with and without diabetes to see the effect of the drug.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

93 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active drug AZ compound

Arm Type

Experimental

Arm Description

AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AZ compound

Intervention Description

AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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 Measure Information:

Title

Percentage Change in Hepatic Fat

Description

Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of <5% is used to distinguish between normal and fatty liver.

Time Frame

baseline, approximately 12 weeks

Title

Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol

Description

Hepatic conversion of [13C] cortisone to [13C] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test.

Time Frame

baseline, approximately 12 weeks

Secondary Outcome Measure Information:

Title

Liver Fibrosis Measured With MRE in kPa

Description

Time Frame

baseline, approximately 12 weeks

Title

Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver)

Description

Total insulin sensitivity (Si) and hepatic insulin sensitivity (Si liver) will be measured with an Oral glucose Tolerance test at baseline and after ~12 weeks of treatment.

Time Frame

baseline, approximately 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: 21-75 Body Mass Index (BMI) >19 kg/m^2 Subjects with biopsy/MRE proven NASH [MRE liver fat ≥ 5%, with elevated liver enzymes ALT <5x upper limit normal (ULN)]. Subjects with NAFLD and MRE shows F0 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rita Basu, MD

Organizational Affiliation

University of Virginia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yogesh Yadav

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22908

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No: There is not a plan to make IPD available

Learn more about this trial

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

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