Growth Hormone Therapy in Liver Cirrhosis

Growth Hormone Therapy and Its Effect on Nitrogen Metabolism and Malnutrition in Liver Cirrhosis

Liver cirrhosis (LC) is a leading cause of morbidity and mortality worldwide. Life- threatening complications of liver cirrhosis are ascites, gastrointestinal bleeding, variceal bleed, hepatic encephalopathy and hepatocellular carcinoma (HCC) which are associated with poor prognosis.The leading causes of liver cirrhosis include excess alcohol consumption, viral hepatitis and non-alcoholic fatty liver disease. Malnutrition is common in end-stage liver disease (cirrhosis) and is often associated with a poor prognosis. It occurs in all forms of cirrhosis with different etiology and prevalence ranges from 65 to 100% depending upon the methods used for nutritional assessment and the severity of liver disease. Nutritional state influences survival in patients with decompensated cirrhosis. Protein malnutrition manifested by reduced skeletal muscle mass and hypoalbuminemia, exist in patients with cirrhosis despite apparent adequate food consumption and these patients have a higher rate of complications and, overall, an increased mortality rate. Also, Malnutrition has significant implications for liver transplantation; patients with poor nutritional status before transplantation have increased complications and higher mortality rates postoperatively. Screening all patients with chronic liver disease for nutritional abnormalities can identify those at risk of developing preventable complications.

Malnutrition is commonly associated with protein catabolism and the protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3.

GH therapy in cirrhosis has been shown to improve nitrogen economy and to improve the GH resistance in a small pilot study by Donaghy et al. Also, GH therapy of short duration has shown to increase IGF1 levels, IGFBP-3 levels in patients of cirrhosis. GH therapy has also shown to improve liver regeneration and protein synthesis after hepatectomy in patients of HCC with cirrhosis.

However there is scarcity of data on clinical impact of long term administration of GH therapy in patients of cirrhosis. Hence, we undertook the present study to study the effect of growth hormone on nitrogen economy, malnutrition and liver regeneration in patients with cirrhosis.

Study Overview

• Status: Completed
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Drug: Standard Medical Therapy; Drug: Growth Hormone

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Decompensated Cirrhosis of liver irrespective of etiology

Exclusion Criteria:

• Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF)
• Splenic diameter of more than 18 cm
• Concomitant HCC or other active malignancy
• Upper gastrointestinal bleeding in the previous 7 days
• Portal vein thrombosis
• Severe renal dysfunction as defined by creatnine > 1.5mg/dl
• Severe cardiac dysfunction
• Uncontrolled diabetes (Hb A 1c ≥ 9) or diabetic retinopathy
• Acute infection or disseminate intravascular coagulation
• Active alcohol abuse in last 3 months
• Known hypersensitivity to GH
• HIV co-infection
• Pregnancy
• Refusal to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Medical Therapy; Standard medical therapy: diuretics, lactulose, rifaximin, diuretics, albumin infusion, nutritional support (as required)	Drug: Standard Medical Therapy; Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required
Active Comparator: Growth hormone; Growth Hormone: GH therapy is initiated at a low dose of 1U/day and titrated slowly upward to a maximum dose of 3U/day (based on IGF-1 levels) subcutaneously for 1 year.	Drug: Standard Medical Therapy; Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required; Drug: Growth Hormone; GH therapy is initiated at a low dose of 1U/day and titrated slowly upward to a maximum dose of 3U/day (depending on IGF-1 levels) subcutaneously for 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Nutritional status based on CT L3 SMI score.	Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in BMI		One Year
Improvement in Mid arm muscle circumference(MAMC)		One year
Improvement in hand grip strength	Hand grip strength will be measured with the hydraulic hand dyanamometer in Kg/force.	One year
Clinical improvement in liver function	Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed	One Year
Biochemical improvement in liver function	Improvment in MELD score	One year
Improvement in Quality of life	Quality of life will be assessed using SF-36V2 Health Survey questionnaire	One Year
Improvement in liver regeneration	By measuring hepatic parenchymal cell specific marker (CD 133) and cell proliferation marker (Ki-67) by immunohistochemistry.	One Year

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 30, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: cirrhosis; Growth hormone
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: GH in cirrhosis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No