Growth Hormone Therapy in Liver Cirrhosis

Cirrhosis, Liver Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03420144
• Other study ID #: GH in cirrhosis
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 15, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: April 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Standard Medical Therapy
Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required
• 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.

Locations

Country	Name	City	State
India	Post Graduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

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