Clinical Effects of New Approach on Patients With Non-alcoholic Steatohepatitis

NCT06105060 | Completed Early Phase 1

• 1 other identifier: Comparative study of NASH
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate and compare the protective outcomes of using Rosuvastatin, Vitamin E, and N-acetyl cysteine in Egyptian patients with NASH. The primary endpoint of this 6-month study would be an improved degree of fibrosis with no worsening of NASH or NASH resolution with no worsening of fibrosis and steatosis that the study considered successful if either 1ry endpoint is met. The secondary endpoint of this study is the improvement of biochemical markers related to steatosis, inflammation, oxidative stress, insulin resistance, and liver fibrosis.

Conditions

Non-alcoholic Steatohepatitis

Keywords

Rosuvastain; N-Acetyl Cysteine; Vitamine E; NASH; Fibroscan

Outcome Measures

Primary Outcomes (16)

• Blood pressure

  (systolic blood pressure/diastolic blood pressure in mmHg normal blood pressure is 120/80 mmHg).

  6 months

• Hight

  In meters (m) .

  6 months

• Weight

  in Kilograms (kg)

  6 months

• Waist circumference

  in centimeters (cm).

  6 months

• Body mass index (BMI)

  The BMI calculation divides an adult\'s weight in kilograms (kg) by their height in meters (m) \^2. (BMI in kg/m\^2).

  6 months

• Clinical examination

  Abdominal ultrasound: to examine right upper quadrant pain or dullness, Mild or moderate hepatomegaly, and The appearance of a hyperechoic liver (showing more echogenicity than the kidneys), vascular blurring, and deep attenuation on ultrasonography are consistent with liver steatosis. and the appearance of bright liver)

  6 months

• FibroScan-AST (FAST Score):

  Base line and at the end of the study period 3months * Steatosis or /and fibrosis Grade of the liver is examined by Fibroscan® of the liver tissue. * The FAST score was calculated using \[e ˆ(- 1·65 + 1·07 × In(LSM) + 2·66∗10-8 × CAP3 - 63.3 × AST-1)\]/\[1 + e ˆ (- 1·65 + 1·07 × In(LSM) + 2·66∗10-8 × CAP3 - 63.3 × AST-1)\] as carried out by Scoring system were used to determine: A-fibrosis staging (F0-F4). For F0-F1, LSM \<7.9 kPa; for F2, LSM of 7.9 to \<8.8 kPa; for F3, LSM of 8.8 to \<11.7 kPa; and for F4 LSM ≥11.7 kPa. B-steatosis grade (S0-S3) to determine the presence of NAFLD. S0 was defined as a CAP \<248 dB/m (\<10% steatosis); S1 as CAP of 248 to \<268 dB/m (10% to \<33% steatosis (mild)); S2 as CAP of 268 to \<280 dB/m (33% to \<66% steatosis (moderate)); and S3 as CAP ≥280 dB/m (≥66% steatosis (severe))

  6 months

• Liver Fibrosis Index FIB-4 score (FIB-4 score):

  Platelets count ( PLT) with FIB-4 score. The formula for FIB-4 is: Age (\[yr\] x AST \[U/L\]) / ((PLT \[10(9)/L\]) x (ALT \[U/L\])(1/2)). The value of FIB-4 below 1.30 is considered as low risk for advanced fibrosis. The value of FIB-4 over 2.67 is considered as high risk for advanced fibrosis. The value between 1.30 and 2.67 are considered as intermediate risk of advanced fibrosis.

  6 months

• Fasting blood glucose level

  This is by venous blood sample collection in order to assess: Fasting blood glucose level, Normal level between 70 mg/dL and 110 mg/dL .

  6 months

• Homeostasis Model Assessment (HOMA-IR),

  This is by venous blood sample collection in order to assess: Fasting insulin with calculation of Homeostasis Model Assessment (HOMA-IR), Less than 1.0 means you are insulin-sensitive which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance.

  6 months

• Kidney function tests:

  This is by venous blood sample collection in order to assess: Serum urea ( Normal Range (NR): 5 to 20 mg/dl) Serum creatinine (NR For adult men, 0.74 to 1.35 mg/dL and For adult women, 0.59 to 1.04 mg/dL.

  6 months

• Lipid profile:

  This is by venous blood sample collection in order to assess: Lipid profile: Total cholesterol ( normal level lower than 200mg/dL) High density lipoprotein cholesterol (HDL), normal level is between 40 to 60mg/dL Triglycerides, normal in range when in between 10 to 150 mg/dL. Low-density lipoprotein (normal level is between 70 to 130mg/dL).

  6 months

• Liver function tests:

  This is by venous blood sample collection in order to assess: Alanine transaminase(ALT): The normal range is 4 to 36 U/L Aspartate aminotransferase (AST): The normal range is 8 to 33 U/L Alk. Phospatse:The normal range is 44 to 147 IU/L Gamma-glutamyl transferase (GGT): reference range for adults is 5 to 40 U/L.

  6 months

• Serum Malondialdehyde (MDA) level (nM):

  This is by venous blood sample collection in order to assess: -Malondialdehyde (MDA) is one of the final products of polyunsaturated fatty acids peroxidation in the cells. An increase in free radicals causes overproduction of MDA. Malondialdehyde level is commonly known as a marker of oxidative stress and the antioxidant status in cancerous patients: normal level is.120 nM (SD 36.26)

  6 months

• The NOD-like receptor family protein 3 (ng /ml)

  This is by venous blood sample collection in order to assess: -The NOD-like receptor family protein 3 (Serum NLRP-3 inflammasome): NR is 2.65 (ng /ml), The NLRP3 inflammasome is considered to be a main pathway for proinflammatory cytokine release in the liver and is strongly involved in the pathogenesis of the liver fibrogenesis

  6 months

• Serum cytokeratin-18 (U/L)

  This is by venous blood sample collection in order to assess: -Serum cytokeratin-18 the normal range is between 68 to 3000 U/L CK-18 levels increase as the mean of NASH CK18 is present in huge amount in liver. It is an intermediate filament protein representing 5% of the hepatic proteins.

  6 months

Secondary Outcomes (1)

• Adverse effects of the intervening drugs

  6 months

Study Arms (4)

Group 1 (Rosuvastatin group):

ACTIVE COMPARATOR

40 patients will receive Crestor (Rosuvastatin 20mg/day orally for 6 months).

Drug: Rosuvastatin 20mg

Group 2 (N-acetyl cysteine group (NAC):

ACTIVE COMPARATOR

40 patients will receive high dose of NATURAL TRUTH'S NAC cap 2400 mg /day for 6 months.

Drug: Rosuvastatin 20mg

Group 3 Two separate drugs ("N-acetyl cysteine" and "Rosuvastatin group"):

ACTIVE COMPARATOR

40 patients will receive "NAC dose 2400 mg" and "Rosuvastatin 20mg /day" for 6 months.

Drug: Rosuvastatin 20mg

Group 4 (Control group):

PLACEBO COMPARATOR

40 patients will receive Vitamin E 400 mg twice daily for 6 months.

Drug: Rosuvastatin 20mg

Interventions

Rosuvastatin 20mg DRUG

to evaluate and compare the protective outcomes of using Rosuvastatin, Vitamin E, and N-acetyl cysteine in Egyptian patients with NASH.

Also known as: N-acetyl cysteine, Vitamin E

Group 1 (Rosuvastatin group):; Group 2 (N-acetyl cysteine group (NAC):; Group 3 Two separate drugs ("N-acetyl cysteine" and "Rosuvastatin group"):; Group 4 (Control group):

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: aged ≥18 years.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients are diagnosed to have fatty liver grading 1, 2 or 3 on abdominal ultrasound with Hepatic steatosis index \> 36 to be considered as a NAFLD patient.
• NASH diagnosis using Fibroscan detecting the degree of steatosis and fibrosis.
• NASH diagnosis is by non-invasive Scoring such as (FAST Score) Cytokeratin-18 \>240 U/L Mild to moderate elevation of hepatic liver enzymes: serum aminotransferases (\>2 but \<5 times upper normal limit)
• Stable dietary habits and physical activity pattern.

You may not qualify if:

• Current or history of significant alcohol consumption.
• 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).
• Prior or planned bariatric surgery.
• Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher.
• Evidence of other forms of chronic liver disease as Hepatitis B, Hepatitis C, Wilson's disease, Alpha-1-antitrypsin(A1AT) deficiency, Hemochromatosis, drug-induced liver disease.
• The presence of contra-indications of NAC or rosuvastatin.
• Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial and breast feeding.
• Use of other drugs known to have possible positive effects on steatosis.
• If there are any conditions where fibroscan could be contra-indicated. The patients refuse participating or completing study.

Sponsors & Collaborators

• Beni-Suef University: lead

Study Sites (1)

Tanta university hospital

Tanta, Gharbyia, 6620010, Egypt

Location

Related Publications (18)

• El Hadi H, Vettor R, Rossato M. Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth? Antioxidants (Basel). 2018 Jan 16;7(1):12. doi: 10.3390/antiox7010012.

  PMID: 29337849 BACKGROUND

• Venetsanaki V, Karabouta Z, Polyzos SA. Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis. Eur J Pharmacol. 2019 Nov 15;863:172661. doi: 10.1016/j.ejphar.2019.172661. Epub 2019 Sep 16.

  PMID: 31536725 BACKGROUND

• Basaranoglu M, Basaranoglu G, Senturk H. From fatty liver to fibrosis: a tale of "second hit". World J Gastroenterol. 2013 Feb 28;19(8):1158-65. doi: 10.3748/wjg.v19.i8.1158.

  PMID: 23483818 BACKGROUND

• Tzanaki I, Agouridis AP, Kostapanos MS. Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J Hepatol. 2022 Jan 27;14(1):119-139. doi: 10.4254/wjh.v14.i1.119.

  PMID: 35126843 BACKGROUND

• Ioannou GN, Van Rooyen DM, Savard C, Haigh WG, Yeh MM, Teoh NC, Farrell GC. Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH. J Lipid Res. 2015 Feb;56(2):277-85. doi: 10.1194/jlr.M053785. Epub 2014 Dec 17.

  PMID: 25520429 BACKGROUND

• Ahsan F, Oliveri F, Goud HK, Mehkari Z, Mohammed L, Javed M, Althwanay A, Rutkofsky IH. Pleiotropic Effects of Statins in the Light of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. Cureus. 2020 Sep 14;12(9):e10446. doi: 10.7759/cureus.10446.

  PMID: 33072455 BACKGROUND

• Schierwagen R, Maybuchen L, Hittatiya K, Klein S, Uschner FE, Braga TT, Franklin BS, Nickenig G, Strassburg CP, Plat J, Sauerbruch T, Latz E, Lutjohann D, Zimmer S, Trebicka J. Statins improve NASH via inhibition of RhoA and Ras. Am J Physiol Gastrointest Liver Physiol. 2016 Oct 1;311(4):G724-G733. doi: 10.1152/ajpgi.00063.2016. Epub 2016 Sep 15.

  PMID: 27634010 BACKGROUND

• Kargiotis K, Katsiki N, Athyros VG, Giouleme O, Patsiaoura K, Katsiki E, Mikhailidis DP, Karagiannis A. Effect of rosuvastatin on non-alcoholic steatohepatitis in patients with metabolic syndrome and hypercholesterolaemia: a preliminary report. Curr Vasc Pharmacol. 2014 May;12(3):505-11. doi: 10.2174/15701611113119990009.

  PMID: 24805248 BACKGROUND

• Antonopoulos S, Mikros S, Mylonopoulou M, Kokkoris S, Giannoulis G. Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis. 2006 Jan;184(1):233-4. doi: 10.1016/j.atherosclerosis.2005.08.021. Epub 2005 Oct 5. No abstract available.

  PMID: 16168995 BACKGROUND

• Gentric G, Maillet V, Paradis V, Couton D, L'Hermitte A, Panasyuk G, Fromenty B, Celton-Morizur S, Desdouets C. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. J Clin Invest. 2015 Mar 2;125(3):981-92. doi: 10.1172/JCI73957. Epub 2015 Jan 26.

  PMID: 25621497 BACKGROUND

• Hutcheson R, Rocic P. The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: the great exploration. Exp Diabetes Res. 2012;2012:271028. doi: 10.1155/2012/271028. Epub 2012 Jul 9.

  PMID: 22829804 BACKGROUND

• Ore A, Akinloye OA. Oxidative Stress and Antioxidant Biomarkers in Clinical and Experimental Models of Non-Alcoholic Fatty Liver Disease. Medicina (Kaunas). 2019 Jan 24;55(2):26. doi: 10.3390/medicina55020026.

  PMID: 30682878 BACKGROUND

• Van Herck MA, Weyler J, Kwanten WJ, Dirinck EL, De Winter BY, Francque SM, Vonghia L. The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity. Front Immunol. 2019 Feb 6;10:82. doi: 10.3389/fimmu.2019.00082. eCollection 2019.

  PMID: 30787925 BACKGROUND

• de Andrade KQ, Moura FA, dos Santos JM, de Araujo OR, de Farias Santos JC, Goulart MO. Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine. Int J Mol Sci. 2015 Dec 18;16(12):30269-308. doi: 10.3390/ijms161226225.

  PMID: 26694382 BACKGROUND

• Dludla PV, Nkambule BB, Mazibuko-Mbeje SE, Nyambuya TM, Marcheggiani F, Cirilli I, Ziqubu K, Shabalala SC, Johnson R, Louw J, Damiani E, Tiano L. N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants (Basel). 2020 Dec 16;9(12):1283. doi: 10.3390/antiox9121283.

  PMID: 33339155 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.

  PMID: 28714183 BACKGROUND

• Zakaria AY, Badawi R, Osama H, Abdelrahman MA, El-Kalaawy AM. New Approach Combination-Dosed Therapy for Nonalcoholic Steatohepatitis Versus Vitamin E: A Randomized Controlled Trial. Clin Ther. 2025 Aug;47(8):e19-e30. doi: 10.1016/j.clinthera.2025.05.006. Epub 2025 Jun 6.

  PMID: 40480879 DERIVED

• Zakaria AY, Badawi R, Osama H, Abdelrahman MA, El-Kalaawy AM. A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial. Pharmaceuticals (Basel). 2025 Apr 29;18(5):650. doi: 10.3390/ph18050650.

  PMID: 40430469 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Rosuvastatin Calcium; Acetylcysteine; Vitamin E

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cysteine; Amino Acids, Sulfur; Amino Acids; Amino Acids, Peptides, and Proteins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Asmaa Mohammed Hussein, Assis.Prof

  Beni-Suef University

  STUDY CHAIR

• Mona Ahmed Emam, Lecturer

  Beni-Suef University

  STUDY DIRECTOR

• Hasnaa Osama Hamed, Lecturer

  Beni-Suef University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer of Clinical Pharmacy (pharmacy practice department)Faculty of Pharmacy

Model Details: This study will be randomized controlled, parallel and prospective 6-months duration study. Accepted patients will be randomized into 4 groups. The size of the sample is calculated using open EPI software (www.openepi.com) and according to NASH prevalence in Egypt.

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 27, 2023
• Study Start: December 17, 2023
• Primary Completion: June 17, 2024
• Study Completion: June 27, 2024
• Last Updated: February 6, 2025

Record last verified: 2024-09

Locations

EG (1)