Protocol summary

Study aim
A Phase I/II, Randomized, Single-Blind Intervention Trial for Evaluating the Safety and Efficacy of Imatinib in Subjects with Advance fibrosis (grade 3, 4)
Design
A phase I/II clinical trial with control group, double blind labeled and randomized double armed. With a parallel group design of 60 patients and permuted block randomization with block size4.
Settings and conduct
Registration of patients depending on inclusion and exclusion criteria for two parallel groups. All patients and medical doctors are blind about receiving placebo or imatinib.
Participants/Inclusion and exclusion criteria
Males or females between 18-75 years old with a clinically confirmed diagnosis of Fibrosis with grade 3-4 by Metavir score. BMI >25 Negative alcohol screen. Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization; Known cardiovascular disease. Requiring any of the following medications during the duration of the study:History of cirrhosis, hepatic encephalopathy or variceal bleeding.History of hepatocellular carcinoma (HCC)، History of malignancy and serious infections. Females who are pregnant or breastfeeding.
Intervention groups
30 patients will be given standard medication and imatinib. 30 patients will be given standard medication and placebo.
Main outcome variables
Assessment of liver fibrosis score by the FibroScan system; Detecting serological changes of alanine aminotransferase, aspartate aminotransferase serum levels, blood sugar and fasting insulin test, albumin, Bilirubin, complete blood count, Alkaline phosphatase, international normalized ratio, prothrombin time. Detecting changes of the serum inflammation markers: Tumor necrosis factor (TNF)-alpha, Interleukin-6

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20200809048342N1
Registration date: 2020-08-25, 1399/06/04
Registration timing: prospective

Last update: 2020-08-25, 1399/06/04
Update count: 0
Registration date
2020-08-25, 1399/06/04
Registrant information
Name
Kaveh Baghaei
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2243 2516
Email address
kavehbaghaei@sbmu.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-09-05, 1399/06/15
Expected recruitment end date
2021-09-06, 1400/06/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A Phase I/II, Randomized, Double-Blind Intervention Trial for Evaluating the Safety and Efficacy of Imatinib in Subjects with Advance fibrosis
Public title
ٍEffect of imatinib in advance liver fibrosis patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Males or females between 18-75 years old with a clinically confirmed diagnosis of Fibrosis with grade 3-4 by Metavir score. BMI >25 Negative alcohol screen. Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Exclusion criteria:
Known cardiovascular disease. Requiring any of the following medications during the duration of the study:History of cirrhosis based on imaging or clinical criteria and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.History of hepatocellular carcinoma (HCC)History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous carcinoma at the time of Screening visitActive, serious infections that requires parenteral antibiotic or antifungal therapy within 30 days prior to Screening visit. Females who are pregnant or breastfeeding. Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immunomodulating agents (such as systemic corticosteroids, interleukins, interferons). Use of any experimental medications within the last 6 months of Screening Visit. Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements. Familial dyslipidemia Weight loss of >5% within 6 months prior to Screening, based on subject's reporting Currently or participated in a weight loss program within the last 6 months Any history of bariatric surgery Diabetes mellitus Type I Daily alcohol intake >20 ml (2 units)/day for women and 30 ml (3 units)/day for men (on average), as per Alcohol Use Disorders Identification Test (AUDIT) questionnaire at Screening and plan to consume the same alcohol amount referenced above during the trial Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids >10 mg prednisone-equivalent concurrently or within 1 year prior to Screening Uncontrolled or clinically unstable thyroid disease, in the judgment of the Principal Investigator. History or presence of hepatitis B or C or human immunodeficiency virus (HIV) Uncontrolled arterial hypertension Any severe, acute, or chronic medical or psychiatric condition that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the subject inappropriate for entry into this study. Subjects who have previously received imatinib or who have history of hypersensitivity, allergy, intolerance or contraindication to imatinib.
Age
From 18 years old to 75 years old
Gender
Both
Phase
1-2
Groups that have been masked
  • Participant
  • Care provider
Sample size
Target sample size: 60
Randomization (investigator's opinion)
Randomized
Randomization description
Permuted block randomization with block size 4.Participants were assigned to two groups of Imatinib drug and placebo using block randomization method (quadruple blocks with equal volume). This ensures balance in the number of groups. In this study, due to the existence of two treatment groups, for 4 blocks, there will be six different manners as follows: ( Control group=C and Treatment group=T) 1. TTCC 2. TCTC 3. TCCT 4. CCTT 5. CTCT 6. CTTC Randomized selection will be carried out each time by Random allocation software.
Blinding (investigator's opinion)
Double blinded
Blinding description
- All participants (patients) will be inform about research project. - All patients and medical doctors are blind about receiving placebo or imatinib. - Academic researchers are aware about receiving treatments for all patients. - The blind approach would be accomplished by giving the doctor unknown sealed drug or placebo, hence, both the physician and the patients are blind in terms of medication and placebo.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of shahid beheshti university of medical science
Street address
Research Institute for Gastroenterology and Liver Diseases, taleghani hospital, Arabi st., Velenjak ave., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1985714711
Approval date
2020-07-18, 1399/04/28
Ethics committee reference number
IR.SBMU.RIGLD.REC.1399.032

Health conditions studied

1

Description of health condition studied
liver fibrosis grade3-4
ICD-10 code
K74
ICD-10 code description
Fibrosis and cirrhosis of liver

Primary outcomes

1

Description
Assessment of liver fibrosis score by the FibroScan system;
Timepoint
Before starting the administration, and at the end of the trial
Method of measurement
FibroScan system

2

Description
Detecting serological changes of: alanine aminotransferase serum levels aspartate aminotransferase serum levels Alkaline phosphatase albumin Bilirubin
Timepoint
Before starting the administration, after 3 months and at the end of the trial.
Method of measurement
Serology testing

3

Description
Blood sugar and fasting insulin test
Timepoint
Before starting the administration, after 3 months and at the end of the trial.
Method of measurement
Blood test

4

Description
Complete blood count
Timepoint
Before starting the administration, after 3 months and at the end of the trial.
Method of measurement
Blood test

5

Description
International normalized ratio and prothrombin time
Timepoint
Before starting the administration, after 3 months and at the end of the trial.
Method of measurement
Blood test

6

Description
Detecting changes of the serum inflammation markers: Tumor necrosis factor (TNF)-alpha, Interleukin-6
Timepoint
Before starting the administration and at the end of the trial.
Method of measurement
Serology testing

Secondary outcomes

empty

Intervention groups

1

Description
Intervention group: patients will be given imatinib orally daily for 24 weeks. The dose will be 200mg/day. Sold under the brand names Gleevec. Its chemical formula is C29H31N7O.The importer company of the drug used in this clinical trial is Sobhan Oncology Pharmaceutical Company and its manufacturer is CIPLA Company in India.
Category
Treatment - Drugs

2

Description
Control group: patients will be given placebo orally daily for 24 weeks.
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Gastroenterology and Liver Diseases clinic
Full name of responsible person
Behzad Hatami
Street address
Gastroenterology and Liver Diseases clinic,Research Institute of Gastroenterology & Liver Diseases, Taleghani Hospital, Arabi St. Daneshjo Blvd, Yaman St. Velenjak
City
Tehran
Province
Tehran
Postal code
1985714711
Phone
+98 21 2243 2516
Email
bzd_hatami@yahoo.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Mohammadreza Zali
Street address
Research Institute of Gastroenterology & Liver Diseases, Taleghani Hospital, Arabi St. Daneshjo Blvd, Yaman St. Velenjak
City
Tehran
Province
Tehran
Postal code
1985714711
Phone
+98 21 2243 2525
Email
nnzali@hotmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Shahid Beheshti University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Behzad Hatami
Position
ََAssistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Gastroeterologist
Street address
Research Institute of Gastroenterology & Liver Diseases, Taleghani Hospital, Arabi St. Daneshjo Blvd, Yaman St. Velenjak, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1985714711
Phone
+98 21 2243 2516
Email
bzd_hatami@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Kaveh Baghaei
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Biology
Street address
Research Institute of Gastroenterology & Liver Diseases, Taleghani Hospital, Arabi St. Daneshjo Blvd, Yaman St. Velenjak
City
Tehran
Province
Tehran
Postal code
1985714711
Phone
+98 21 2243 2516
Fax
Email
kavehbaghaei@sbmu.ac.ir

Person responsible for updating data

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Helia Alavifard
Position
Researcher
Latest degree
Master
Other areas of specialty/work
Laboratory Medicine
Street address
Gastroenterology and Liver Diseases clinic,Research Institute of Gastroenterology & Liver Diseases, Taleghani Hospital, Arabi St. Daneshjo Blvd, Yaman St. Velenjak
City
Tehran
Province
Tehran
Postal code
1985714711
Phone
+98 21 2243 2516
Fax
Email
alavifardh@yahoo.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Not applicable
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
Part of data which is related to main outcome could be share
When the data will become available and for how long
starting in 2021
To whom data/document is available
It would be available for people working in academic institutions and those are in businesses can also apply to receive it.
Under which criteria data/document could be used
It is depend on requests.
From where data/document is obtainable
Corresponding: Dr. Behzad Hatami "bhz_hatami@yahoo.com" Dr. Kaveh Baghaei "kavehbaghai@gmail.com"
What processes are involved for a request to access data/document
-Request - Early consideration in 1 week - Conversations - Provide possible request between 2-4 weeks
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