Clinical trial NCT01384578: Pentoxiphylline and Vitamin E Versus Vitamin E in Patients With Non- Alcoholic Steatohepatitis
Official title: A Randomized Controlled Project to Study the Efficacy of Combined Pentoxiphylline and Vitamin E Versus Vitamin E in Patients With Non- Alcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Non Alcoholic Steatohepatitis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2011-06-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 120 patients of biopsy proven NASH will be randomized into two groups. Cases group will receive combination of pentoxiphylline and Vitamin E, and control group will receive only Vitamin E.

Detailed description: The investigators plan to randomise 120 patients of biopsy proven NASH into cases and control groups.

Baseline investigations:

Clinical characteristics

* Age
* Gender
* Anthropometry (BMI, waist circumference, waist- hip ratio, triceps skin fold thickness, mid arm circumference)
* Alcohol intake should be nil

Laboratory characteristics

* Hemogram, INR, KFT
* LFT (especially ALT, GGT) , APRI (AST to platelet ratio)
* Fasting Lipid Profile
* Other possible etiologies of liver disease (viral markers, ferritin, ANA, IgG, ceruloplasmin )
* HOMA-IR (II)
* Serum uric acid levels Liver stiffness
* Fibroscan
* MR elastography Radiological characteristics
* USG abdomen Variceal status by UGI endoscopy Alpha fetoprotein Pro- inflammatory markers
* TNF-alpha, IL-6, adiponectin, leptin and osteopontin Liver biopsy and NAS score

Eligibility criteria: Inclusion Criteria:

* Age 18 to 70 years
* Persistently abnormal ALT \>1.2 times upper limit of normal
* Histological evidence of NASH/cirrhosis on liver biopsy. ( The minimal criteria for diagnosis of NASH included the presence of lobular inflammation and either ballooning of cells or perisinusoidal or pericellular fibrosis in Zone 3 of the hepatic acinus)

Exclusion Criteria:

* A known case of Type 2 diabetes mellitus on treatment
* Alcohol intake of more than 40gm / week
* If they had evidence of cirrhosis with significant portal hypertension
* Ongoing total parenteral nutrition/ jejunal-ileal bypass
* Other known liver disease (Hepatitis A to E, autoimmune liver disease, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis)
* Medication like estrogens, amiodarone, MTx, tamoxifen, ATT
* Pregnancy or lactation
* Hypersensitivity to methylxanthines (e.g., caffeine, theophylline, theobromine )
* Recent retinal/cerebral hemorrhage
* Acute myocardial infarction or severe cardiac arrhythmias
* Impaired renal function
* Hypothyroidism

Primary outcomes:
measure: histological outcome in the form of improvement or non- progression in hepatocyte injury and fibrosis (NAS score).
timeFrame: 3 Months
Secondary outcomes:
measure: Response in form of anthropometry , HOMA-IR, fasting lipid profiles, biochemical response in form of normalization of ALT and AST levels and reduction in uric
timeFrame: 3 Months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of liver and Biliary Sciences
state: Delhi
Study officials:
affiliation: Institute of Liver & Biliary Sciences (ILBS)
name: Shiv Kumar Sarin, MD,DM
role: STUDY_DIRECTOR
References:
citation: Kedarisetty CK, Bhardwaj A, Kumar G, Rastogi A, Bihari C, Kumar M, Sarin SK. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study. Indian J Gastroenterol. 2021 Feb;40(1):41-49. doi: 10.1007/s12664-020-01131-x. Epub 2021 Mar 27.