An Evaluation of the Safety and Efficacy of NTZ on Collagen Turnover in NASH Patients With Fibrosis
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|ClinicalTrials.gov Identifier: NCT03656068|
Recruitment Status : Recruiting
First Posted : September 3, 2018
Last Update Posted : January 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Non-alcoholic Steatohepatitis Fatty Liver Fibrosis, Liver Compensated Cirrhosis||Drug: Nitazoxanide 500mg BID||Phase 2|
Based on the anti-fibrotic properties demonstrated in the animal models of fibrosis, this proof of concept clinical study aims at evaluating NTZ in patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage 2 and 3. Although NTZ has been evaluated in liver disease populations (viral hepatitis C) up to 60 weeks, this is the first study evaluating NTZ treatment in a population with NASH induced stage 2 and 3 fibrosis. The aim of this study is to evaluate the safety and tolerability of NTZ 500 mg BID after 24 weeks of treatment in this population.
This proof of concept study will also evaluate the anti-fibrotic effect of NTZ as a secondary objective.
The methods of evaluation of fibrosis will include an innovative method of metabolic labeling. This approach is based on the concept that liver status can be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turn-over rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients will be given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry is used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results are expressed as fractional synthesis rate of these proteins (FSR). This method has been previously published (Decaris et al, 2017).
Other non-invasive methods will be used to evaluate the liver stiffness changes after NTZ treatment: Magnetic Resonance Elastography (MRE) and FibroScan®.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Monocentric, Open-Label, Proof of Concept Study to Evaluate the Safety and Efficacy of NTZ at 500mg Twice Daily on Collagen Turnover in Plasma in NASH Patients With Fibrosis Stage 2 or 3|
|Actual Study Start Date :||December 15, 2018|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||October 2020|
Experimental: Open label NTZ
Open label study. All patients will receive study drug.
Drug: Nitazoxanide 500mg BID
Patients will receive 500mg of Nitazoxanide BID daily for 24 weeks
- Number of participants with treatment related adverse events and serious adverse events [ Time Frame: 24 weeks ]
- Percent change in Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. [ Time Frame: 24 weeks ]
- Change in liver stiffness from baseline to end or treatment as evaluated by FibroScan® [ Time Frame: 24 weeks ]Range of FibroScan scores 0-75
- Change in liver stiffness from baseline to end of treatment as evaluated through the use Magnetic Resonance Elastography (MRE) [ Time Frame: 24 weeks ]kPa values (1-10) will be measured
- Change in FIB4 (fibrosis serum biomarker) at baseline to 12 weeks treatment and 24 weeks of treatment [ Time Frame: 24 weeks ]Score range 1-4, to determine fibrosis
- Change in Fibrotest (biomarker test) results at baseline to 12 weeks to 24 weeks [ Time Frame: 24 weeks ]Serum blood test, to determine fibrosis
- Change in NAFLD Fibrosis Score at baseline to 12 weeks to 24 weeks [ Time Frame: 24 weeks ]Calculated based on age, BMI, AST, ALT, Platelets and Albumin values to determine fibrosis
- Change in Fibrometer results at baseline to 12 weeks to 24 weeks to determine fibrosis [ Time Frame: 24 weeks ]Family of blood tests
- Change in HepaScore results at baseline to 12 weeks to 24 weeks [ Time Frame: 24 weeks ]Liver fibrosis blood panel
- Change in Enhanced Liver Fibrosis (ELF) Score (ELFTM) at baseline to 12 weeks to 24 weeks [ Time Frame: 24 weeks ]Combination of three serum biomarkers to obtain level of fibrosis of liver
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): NCT03656068
|Contact: Gail Hinksonemail@example.com|
|Contact: Sandra Owersfirstname.lastname@example.org|
|United States, Texas|
|Pinnacle Clinical Research||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Sandra Owers 210-982-0320|
|Principal Investigator: Stephen Harrison, MD|
|Principal Investigator:||Stephen Harrison, MD||Pinnacle Clinical Research|