The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease

NCT02546609 | Completed Phase 2 Results

• 1 other identifier: NS-0200-01
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 13

Brief Summary

The goal of this study is to determine if NS-0200 can reduce the amount of liver fat in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). This study will compare two doses of NS-0200 to placebo in NAFLD patients.

Conditions

NAFLD

Outcome Measures

Primary Outcomes (1)

• Change in Hepatic Fat

  To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI).

  Baseline, Day 112

Secondary Outcomes (11)

• Change in Serum AlanineAaminotransferase (ALT) Levels

  Baseline, Day 112

• Change in Circulating Cytokeratin 18 Fragments (M30)

  Baseline, Day 112

• Change in Heamoglobin A1c (HbA1c)

  Baseline, Day 112

• Change in Fasting Glucose

  Baseline, Day 112

• Change in Insulin

  Baseline, Day 112

Study Arms (3)

Leu Met Sil 0.5mg

EXPERIMENTAL

Leu-Met-Sil 0.5: 3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Drug: Leu-Met-Sil 1.0

Leu Met Sil 1.0mg

EXPERIMENTAL

Leu-Met-Sil 1.0: 3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Drug: Leu-Met-Sil 0.5; Drug: Leu-Met-Sil 1.0

Placebo

PLACEBO COMPARATOR

Placebo: 3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Drug: Placebo

Interventions

Leu-Met-Sil 0.5 DRUG

NS-0200 low dose

Also known as: NS-0200-0.5

Leu Met Sil 1.0mg

Leu-Met-Sil 1.0 DRUG

NS-200 high dose

Also known as: NS-0200-1.0

Leu Met Sil 0.5mg; Leu Met Sil 1.0mg

Placebo DRUG

Placebo

Also known as: Control arm

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 at study entry.
• Is male, or female and, if female, meets all of the following criteria:
• Not breastfeeding
• Post-menopausal or negative serum pregnancy test result (human chorionic gonadotropin, beta subunit \[β-hCG\]) at Screening /Visit 1 (Day-14/Week-2) (not required for hysterectomized females)
• If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods \[male condom with spermicide, with or without cervical cap or diaphragm\], implants, injectables, oral contraceptives \[must have been using for at least the last 3 months\], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study.
• Has been diagnosed with NAFLD via CT (positive for excess liver fat), ultrasound (positive for excess liver fat), MRI (PDFF showing \> 15% liver fat) or via biopsy (showing \>33% fat) within the past six months. If diagnosis was between 3 and 6 months prior to Screening, an ultrasound (positive for excess liver fat) is required prior to the Screening /Visit 1 (Day-14/Week-2) MRI.
• Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2 (Day-7/Week-1)
• Has had ALT levels \>30 U/L for men, \>19 U/L for women measured within 8 weeks of enrollment
• Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)
• Has a BMI between 25kg/m2 and 40 kg/m2
• Otherwise stable health for preceding twelve weeks
• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or with abnormalities consistent with NAFLD.
• Is able to read, understand, and sign the informed consent forms (ICF) and, when applicable, an authorization to use and disclose protected health information form (consistent with Health Insurance Portability and Accountability Act of 1996 \[HIPAA\] legislation), communicate with the investigator, and understand and comply with protocol requirements.

You may not qualify if:

• Clinically significant renal dysfunction defined as a serum creatinine concentration \>1.4 mg/dL (females) or \>1.6 mg/dL (males) or a blood urea nitrogen concentration \>45 mg/dL at screening.
• Use of any of the following medications:
• Metformin
• Combination drugs that include Metformin
• Sildenafil
• Tadalafil
• Vardenafil
• Pioglitazone
• Rosiglitazone
• Short acting insulins
• An alpha blocker
• Oral nitrates
• Medications associated with increased hepatic steatosis
• Insulins
• OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)

Sponsors & Collaborators

• NuSirt Biopharma: lead

Study Sites (13)

Catalina Research Institute

Chino, California, 91710, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Rocky Mountain Research

Wheat Ridge, Colorado, 80033, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30312, United States

Location

GI Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Sterling Research

Cincinnati, Ohio, 45246, United States

Location

Premier Clinical Research

Clarksville, Tennessee, 37043, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Quality Medical Research

Nashville, Tennessee, 37211, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.

  PMID: 36318027 DERIVED

• Zemel MB, Kolterman O, Rinella M, Vuppalanchi R, Flores O, Barritt AS 4th, Siddiqui M, Chalasani N. Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. Obesity (Silver Spring). 2019 Jan;27(1):59-67. doi: 10.1002/oby.22346.

  PMID: 30569637 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Barbara Cannon
• Organization: Nusirt Biopharma Inc.

BCannon@nusirt.com

615-656-7898

Study Officials

• Orville Kolterman, MD

  NuSirt Biopharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2015
• First Posted: September 11, 2015
• Study Start: November 19, 2015
• Primary Completion: November 30, 2016
• Study Completion: January 31, 2017
• Last Updated: May 2, 2018
• Results First Posted: May 2, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)