Slctr

Comparison of Delta-tocotrienol and Alpha-tocopherol Effects on Biochemical Markers, Micro-RNA Expression and Hepatic Steatosis in Patients with Non-Alcoholic Fatty Liver Disease

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SLCTR Registration Number

SLCTR/2019/038

Date of Registration

16 Oct 2019

The date of last modification

Oct 16, 2019

Application Summary

Scientific Title of Trial

Comparison of Delta-tocotrienol and Alpha-tocopherol Effects on Biochemical Markers, Micro-RNA Expression and Hepatic Steatosis in Patients with Non-Alcoholic Fatty Liver Disease

Public Title of Trial

A non randomized controlled trial on the comparison of Delta-tocotrienol and Alpha-tocopherol Effects on Non-Alcoholic Fatty Liver Disease.

Disease or Health Condition(s) Studied

Non-Alcoholic Fatty Liver Disease

Scientific Acronym

None

Public Acronym

None

Brief title

Comparison of Delta-tocotrienol and Alpha-tocopherol Effects on Non-Alcoholic Fatty Liver Disease

Universal Trial Number

U1111-1231-9901

Any other number(s) assigned to the trial and issuing authority

PHD-Path-18-4/READ-IRB/19/413

Trial Details

What is the research question being addressed?

Is delta-tocotrienol more effective than alpha-tocopherol in improving Nonalcoholic fatty liver disease?

Type of study

Interventional

Study design

Allocation

Randomized controlled trial

Masking

Double blinded : Participants, Investigators

Control

Active

Assignment

Parallel

Purpose

Treatment

Study Phase

Phase 2

Intervention(s) planned

Study setting: The study will be conducted at Mega Medical Complex Hospital in collaboration with Armed Forces Institute of Pathology and Armed Forces Institute of Radiology (AFIRI) Rawalpindi Pakistan

Randomization: The patients with NAFLD will be assigned to one of the two arms i.e. arm A or arm B by simple randomization.

Details of intervention: Patients in the arm A will receive a capsule containing Delta-tocotrienol 300 mg twice daily orally (one in the morning and one in the evening) for 24 weeks. Patients in the arm B will receive a matching capsule containing Alpha-tocopherol 400 IU(268 mg) for the same frequency and duration.

During the study period, participants in both arms will be requested to avoid consuming herbs and vitamin supplements

Masking will be carried out as follows: Participants: Blinded Investigators: Blinded

Inclusion criteria

Both men and women
Aged 20-70 years
Presence of fatty liver on abdominal CT scan with a liver to spleen (L/S) attenuation ratio of less than 1.1 (indicating more than 30% hepatic steatosis)
Fatty Liver Index (FLI) of equal to or more than 60
Alanine transaminase (ALT) within reference range or mildly raised i.e. not greater than 3 times the upper limit of 42 IU/L in male and 36 IU/L in female

Exclusion criteria

Chronic hepatitis B and C
Alcoholic fatty liver Disease
Autoimmune liver disease
History or clinical evidence of liver cirrhosis
Hemochromatosis, Wilson’s disease
Diabetic patients with Hemoglobin A1c (HbA1c) more than 8.5%
A history of cardiovascular disease, pulmonary disease & renal disease
Pregnant or lactating females or females planning to become pregnant during the study period Patients on oral insulin-sensitizing agents, herbs and vitamin supplements 10.Patients under treatment with tamoxifen, methotrexate, amiodarone, diltiazem or other drugs able to induce fatty liver

Primary outcome(s)

1. 1.Mean reduction in Fatty Liver Index (FLI) from baseline to week 24 and 48	[ Baseline and week 24 and week 48 ]
2. Mean reduction in the measurement of Liver Fat on CT scan (indicated by an increase in the liver-to-spleen (L/S) attenuation ratio)	[ Baseline and week 24 and week 48 ]
3. Mean reduction in the measurement of Fibrosis score-4 (FIB-4)	[ Baseline and week 24 and week 48 ]

Secondary outcome(s)

Mean reduction in the measurement of Alanine tranaminase (IU/L) Aspartate transaminase (IU/L) and Gamma-glutamyl transferase (IU/L)
Mean reduction in the measurement of Fasting plasma glucose (mmol/L), Insulin (mIU/L) and Homeostatic Model Assessment for Insulin Resistance (HOMA IR)
Mean reduction in the measurement of serum High sensitivity C-reactive protein (mg/L), Interleukin-6 (pg/mL), Tumor necrosis factor alpha (pg/mL) and Leptin (ng/mL)
Mean increase in the measurement of serum Adiponectin (µg/mL)
Mean reduction in the measurement of serum Malondialdehyde (µmol/L)
Mean reduction in the measurement of serum Cytokeratin18 (CK18-M30) (mIU/ml)
Mean reduction in measurement of serum Total cholesterol (mmol/L), Triglycerides (mmol/L) and LDL-cholesterol (mmol/L)
Mean reduction in the measurement of Aspartate Aminotransferase to Platelet Count Ratio Index (APRI)
Mean reduction in the measurement of NAFLD Fibrosis Score (NFS)
Mean fold change in Circulatory miRNAs (miR-122-5p, miR-192-5p, miR-34a-5p, miR-103a, miR-451, miR-21)

[
Baseline, week 24 and week 48
]

Target number/sample size

100 (50 per arm)

Countries of recruitment

Pakistan

Anticipated start date

2019-10-20

Anticipated end date

2021-03-31

Date of first enrollment

Date of study completion

Recruitment status

Pending

Funding source

National University of Medical Sciences Rawalpindi, Pakistan

Regulatory approvals

State of Ethics Review Approval

Status

Approved

Date of Approval

2019-04-17

Approval number

PHD-Path-18-4/READ-IRB/19/413

Details of Ethics Review Committee

Name:	IRB, Armed Forces Institute of Pathology, NUMS, Rawalpindi
Institutional Address:	READ Department, Armed Forces Institute of Pathology, NUMS, Rawalpindi, Pakistan
Telephone:	+92-51 5176397
Email:	read.afip@gmail.com

Contact & Sponsor Information

Contact person for Scientific Queries/Principal Investigator

Dr. Dilshad Ahmed Khan
Professor of Pathology
National University of Medical Sciences (NUMS), Rawalpindi
+92 51 9270676
+92 300 5147938
+92 51 9270677
dakhan@cpsp.edu.pk

Contact Person for Public Queries

Dr. Muhammad Amjad Pervez
PhD Scholar
Armed forces institute of Pathology (AFIP), National University of Medical Sciences (NUMS), Rawalpindi
+92 346 5506000
+92 346 5506000
+92 51 9270677
amjad.pervez@numspak.edu.pk

Primary study sponsor/organization

National University of Medical Sciences

The Mall Rawalpindi 46000, Pakistan
92-51 5176397

read.afip@gmail.com

Secondary study sponsor (If any)

Trial Completion details

Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

Yes

IPD sharing plan description

Individual participant data that underlie the results being reported, after de-identification (text, tables, figures and appendices) will be shared.Study protocol, statistical analysis will be included.Data will be shared following the publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared to achieve the aims in an approved proposal.Data will be available for 5 years from the time of publication.

Study protocol available

Protocol version and date

Not Available

Protocol URL

Not Available

Results summary available

Date of posting results

Date of study completion

Final sample size

Date of first publication

Link to results

Brief summary of results