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the Efficacy and Safety of Diosmin on Non-diabetic Patients With Non-alcoholic Steatohepatitis.

Primary Purpose

Non Alcoholic Steatohepatitis

Status
Recruiting
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Diosmin
Placebo
Sponsored by
Tanta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Alcoholic Steatohepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Non-diabetic patients with or without hypertension. Both males and females. Age >18 years old. Overweight and obese patient: Body mass index (BMI) ≥ 25 kg/m2 <.40 kg/m2 Patients with established diagnosis of NASH based on liver ultrasonography, mild to moderate elevation in aminotransferase activities (>2 but <5 times upper limit of normal), hepatic steatosis index (HIS) >36, HAIR score of 2 or 3. Exclusion Criteria: Patients with BMI ≥ 40 kg/m2 Patients with type 2 diabetes mellitus (T2DM) on the basis of a fasting plasma glucose (FPG) level ≥ 126 mg/dl (7mmol/L) or glycated hemoglobin (HbA1c) > 6.5% (48 mmol/mol). Alcohol consumption greater than 20 g per day for women or greater than 30 g for men for at least three consecutive months over the past 5 years. History of viral hepatitis, hemochromatosis, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, biliary obstruction, alpha-1 antitrypsin deficiency. Patients on medications interfere with lipid and carbohydrate metabolism (statin, fibrate, beta blockers, thiazide, corticosteroids, etc). Patients with cancer or with a history of cancer. Patients with thyroid disorder. Patients on medications associated with steatosis such as NSAIDs, amiodarone, tamoxifen, estrogen, sodium valproate, corticosteroids, and methotrexate. Patients with inflammatory diseases (rheumatoid arthritis, ulcerative colitis, etc). Patients on supplements known to have antioxidant activity such as vitamin E, vitamin C, zinc, and selenium. Patient with a history of cardiovascular diseases. Patients with arrhythmia or altered heart rate. Patients on blood thinning agents (warfarin, clopidogril, aspirin, etc), anticonvulsants (carbamazepine and phenytoin), muscle relaxants (chlorzoxazone) and non-steroidal anti-inflammatory drugs (diclofenac( in order to avoid potential pharmacodynamics and pharmacokinetic drug interactions with diosmin. Pregnant and breastfeeding women. Females on oral contraceptive pills will be also excluded.

Sites / Locations

  • Tanta UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

diosmin group

placebo group

Arm Description

(Diosmin group; n = 24):will receive 600 mg twice daily

placebo group n=24 :will receive placebo twice daily

Outcomes

Primary Outcome Measures

the change in ultrasound including NAFLD fibrosis scor
The change in ultrasound through decreasing liver echogenicity, Lower echoes in the hepatic parenchyma, no vessel blurring, and decrease narrowing of the lumen of the hepatic veins Ultrasonography Fatty Liver Indicator (US-FLI) <2
The change in fibrosis risk score
Score <-1.455 predicts absence of significant fibrosis (F0-F2)

Secondary Outcome Measures

The secondary outcome is the change in biological biomarkers and other measured parameters
The change in liver panel
secondary outcome is the change in biological biomarkers and other measured parameters
The change in the Homeostasis Model Assessment-insulin resistance (HOMA-IR)
secondary outcome is the change in biological biomarkers and other measured parameters
The change in biological parameters (MDA, TNF-α, and TGF-β1)

Full Information

First Posted
June 21, 2023
Last Updated
July 5, 2023
Sponsor
Tanta University
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1. Study Identification

Unique Protocol Identification Number
NCT05942547
Brief Title
the Efficacy and Safety of Diosmin on Non-diabetic Patients With Non-alcoholic Steatohepatitis.
Official Title
Clinical Study Evaluating the Efficacy and Safety of Diosmin on Non-diabetic Patients With Non-alcoholic Steatohepatitis.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2023 (Anticipated)
Primary Completion Date
October 10, 2023 (Anticipated)
Study Completion Date
June 10, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a randomized, controlled study evaluating diosmin tablets administered daily for 3 months. The purpose of the study is to evaluate the efficacy and safety of diosmin on non-diabetic patients with non-alcoholic steatohepatitis.
Detailed Description
The aim of the study is to test the implication of diosmin in fatty liver disease through evaluation of its efficacy and safety in non-diabetic patients with nonalcoholic steatohepatitis (NASH). Patients and Methods: This study will be a randomized double-blind placebo-controlled parallel study that will involve 48 non-diabetic patients with confirmed diagnosis of NASH. The patients will be recruited from outpatient Clinic of the internal medicine department, Tanta University Hospital, Tanta, Egypt. The diagnosis of NASH will be confirmed by imaging technique (increased liver echogenicity, stronger echoes in the hepatic parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins), mild to moderate elevation in aminotransferase activities (>2 but <5 times upper limit of normal), hepatic steatosis index (HIS) >36, HAIR score (hypertension, alanine aminotransferase level, insulin resistance) of 2 or 3 and cytokeratin-18 level >240 IU/L. The patients will be randomized in a 1:1 ratio by a neutral researcher using sealed envelopes methods with assignment codes for each available allocation to receive either diosmin 600 mg twice daily (Diosmin group; n = 24) or placebo twice daily (Placebo group; n = 24). The study duration will be 12 weeks. All participants and will be informed about the benefits and risks of the study. The expected risks that will be clarified to patients include diosmin related adverse effect; stomach pain, diarrhea, headache, skin redness, muscle pain, and altered heart rate. Any unexpected risks that will appear during the course of the research will be clarified to the participants and to the ethical committee on time. The data of the enrolled patients will be confidential. All enrolled patients will give their written informed consents. The study will be carried out between june2023 and june2025.Demography and anthropometric measurements At baseline and after intervention, all participants will be submitted to medical history taking, demography (age, sex, and medication history), physical examination with heart rate evaluation, measurement of weight and height with subsequent calculation of body mass index (BMI)=[Weight (kg)÷ Height2 (m)]. 2. Ultrasonographic examination Ultrasonography of the liver will be carried out at baseline and at the end of the study by the same operator. Ultrasonography Fatty Liver Indicator (US-FLI) is a scoring system ranging 2-8 based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, and difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. 3. Blood samples collection and biochemical measurements Before and after the intervention, 8 ml of venous blood will be withdrawn by antecubital venipuncture from each participant after overnight fasting (12 h fasting period) between 8:30 and 10:30 a.m. into plain test tubes. Three ml of the blood samples will be used for the assessment of complete blood count. The remaining 5 ml of blood will be centrifuged at 3000 rpm for 10 min. The separated serum will be divided into two portions. The first portion will be used for immediate determination of liver panel, fasting lipid profile and fasting blood glucose concentration. The second portion of the serum will be frozen at-80°C until analysis of the remaining parameters including malondialdehyde (MDA), tumor necrosis factor- alpha (TNF-α), fasting insulin and transforming growth factor-beta1 (TGF-β1). Complete blood count (CBC) will be determined by automated hematology analyzer. Liver enzymes (AST, ALT, and GGT) will be determined by kinetic method. Serum albumin level which will be assayed by colorimetric bromocresol green method or other available method. Fasting blood glucose will be determined by glucose oxidase method or glycated hemoglobin (HbA1c%) will be measured by commercially available method Lipid panel including total cholesterol (TC), triglyceride (TG) and HDLC will be assessed by enzymatic colorimetric method. Fasting insulin level will be determined by ELISA. Malondialdehyde (MDA) which will be assessed by colorimetric method. Tumor necrosis factor- alpha (TNF-α) will be determined by ELISA. Serum transforming growth factor-beta1 (TGF-β1) will be determined by ELISA. In addition, prothrombin time (PT) or INR will be assessed regularly at baseline and on monthly basis. 4. Calculated parameters Low density lipoprotein cholesterol (LDL-C) will be calculated using the Friedewald formula17 as follows: [LDL-C=TC- HDL-C- (TG÷5)] provided that TG level is less than 400 mg/dl. Very low density lipoprotein cholesterol will be calculated using the Friedewald formula17 as follows: o VLDL = TG/5. The Homeostasis Model Assessment-insulin resistance (HOMA-IR) 18 will be calculated as follow: o HOMA-IR= (Fasting glucose × fasting insulin/405) when glucose is expressed by mg/dl and insulin is expressed by μIU/ml. Hepatic steatosis index "HSI". Hepatic steatosis index includes gender, history of type 2 diabetes mellitus (T2DM), BMI, alanine transaminase "ALT", and aspartate transaminase "AST". HSI is calculated by the following formula: 8 × (ALT/AST ratio) + BMI + 2 if female and + 2 if diabetic (0 since the study will be conducted on non-diabetic). HAIR score "hypertension, alanine aminotransferase level, insulin resistance". It is calculated from hypertension ≥140/90, ALT >40 and HOMA-IR >5. Presence of one item indicates HAIR score=1. o Presence of two item indicates HAIR score=2. Prescience of the 3 items indicates HAIR score=3. - Fibrosis risk scores: o Fibrosis index based on the 4 factors (FIB-4). FIB-4= Age (years) × AST (IU/l)/[platelet count (109 /L) ×√ ALT (IU/l)]. Aspartate transaminase-to-platelet ratio index (APRI).22 APRI =AST (IU/l)/(upper limit of normal) X 100 /platelet count (109 /L). NAFLD fibrosis score (NFS) which depends on 7 parameters including age, BMI, diabetes, AST, ALT, platelets count, and albumin concentration. Score <-1.455 predicts absence of significant fibrosis (F0-F2). Score ≤ - 1.455- ≤ 0.675 predicts intermediate score Score > 0.675 predicts presence of significant fibrosis (F3-F4).

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This study will be a randomized double-blind placebo-controlled parallel study that will involve 48 non-diabetic patients with confirmed diagnosis of NASH. . The patients will be randomized in a 1:1 ratio by a neutral researcher using sealed envelopes methods with assignment codes for each available allocation to receive either diosmin 600 mg twice daily (Diosmin group; n = 24) or placebo twice daily (Placebo group; n = 24). The study duration will be 12 weeks.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
diosmin group
Arm Type
Experimental
Arm Description
(Diosmin group; n = 24):will receive 600 mg twice daily
Arm Title
placebo group
Arm Type
Placebo Comparator
Arm Description
placebo group n=24 :will receive placebo twice daily
Intervention Type
Drug
Intervention Name(s)
Diosmin
Intervention Description
diosmin 600mg twice daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
twice daily
Primary Outcome Measure Information:
Title
the change in ultrasound including NAFLD fibrosis scor
Description
The change in ultrasound through decreasing liver echogenicity, Lower echoes in the hepatic parenchyma, no vessel blurring, and decrease narrowing of the lumen of the hepatic veins Ultrasonography Fatty Liver Indicator (US-FLI) <2
Time Frame
at baseline then after 3 months
Title
The change in fibrosis risk score
Description
Score <-1.455 predicts absence of significant fibrosis (F0-F2)
Time Frame
at baseline then after 3 months
Secondary Outcome Measure Information:
Title
The secondary outcome is the change in biological biomarkers and other measured parameters
Description
The change in liver panel
Time Frame
at baseline then after 3 months
Title
secondary outcome is the change in biological biomarkers and other measured parameters
Description
The change in the Homeostasis Model Assessment-insulin resistance (HOMA-IR)
Time Frame
at baseline then after 3 months
Title
secondary outcome is the change in biological biomarkers and other measured parameters
Description
The change in biological parameters (MDA, TNF-α, and TGF-β1)
Time Frame
at baseline then after 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Non-diabetic patients with or without hypertension. Both males and females. Age >18 years old. Overweight and obese patient: Body mass index (BMI) ≥ 25 kg/m2 <.40 kg/m2 Patients with established diagnosis of NASH based on liver ultrasonography, mild to moderate elevation in aminotransferase activities (>2 but <5 times upper limit of normal), hepatic steatosis index (HIS) >36, HAIR score of 2 or 3. Exclusion Criteria: Patients with BMI ≥ 40 kg/m2 Patients with type 2 diabetes mellitus (T2DM) on the basis of a fasting plasma glucose (FPG) level ≥ 126 mg/dl (7mmol/L) or glycated hemoglobin (HbA1c) > 6.5% (48 mmol/mol). Alcohol consumption greater than 20 g per day for women or greater than 30 g for men for at least three consecutive months over the past 5 years. History of viral hepatitis, hemochromatosis, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, biliary obstruction, alpha-1 antitrypsin deficiency. Patients on medications interfere with lipid and carbohydrate metabolism (statin, fibrate, beta blockers, thiazide, corticosteroids, etc). Patients with cancer or with a history of cancer. Patients with thyroid disorder. Patients on medications associated with steatosis such as NSAIDs, amiodarone, tamoxifen, estrogen, sodium valproate, corticosteroids, and methotrexate. Patients with inflammatory diseases (rheumatoid arthritis, ulcerative colitis, etc). Patients on supplements known to have antioxidant activity such as vitamin E, vitamin C, zinc, and selenium. Patient with a history of cardiovascular diseases. Patients with arrhythmia or altered heart rate. Patients on blood thinning agents (warfarin, clopidogril, aspirin, etc), anticonvulsants (carbamazepine and phenytoin), muscle relaxants (chlorzoxazone) and non-steroidal anti-inflammatory drugs (diclofenac( in order to avoid potential pharmacodynamics and pharmacokinetic drug interactions with diosmin. Pregnant and breastfeeding women. Females on oral contraceptive pills will be also excluded.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
merna tarek elsaeed
Phone
00201551813013
Email
sgama676@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
amira bahaa ismail
Phone
00201142760505
Email
amira7794.aa@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
tarek mohamed mostafa, professor
Organizational Affiliation
Tanta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tanta University
City
Tanta
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
tanta university
Phone
0020403317928
Email
tanta_unv@unv.tanta.edu.eg

12. IPD Sharing Statement

Plan to Share IPD
No

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