Growth Hormone Therapy in Liver Cirrhosis

NCT ID: NCT03420144

Last Updated: 2023-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2020-06-30

Brief 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.

Conditions

Cirrhosis, Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard Medical Therapy

Standard medical therapy: diuretics, lactulose, rifaximin, diuretics, albumin infusion, nutritional support (as required)

Group Type: ACTIVE_COMPARATOR

Standard Medical Therapy

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Standard Medical Therapy

Intervention Type: DRUG

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

Growth Hormone

Intervention Type: DRUG

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.

Interventions

Standard Medical Therapy

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Dr.Virendra Singh

Professor of Hepatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

Countries

India

References

Kumari S, De A, Kalra N, Singh V. Growth Hormone Therapy in Decompensated Cirrhosis: An Open-Label, Randomized Control Trial. Am J Gastroenterol. 2024 Jan 1;119(1):116-126. doi: 10.14309/ajg.0000000000002300. Epub 2023 Apr 27.

Reference Type: DERIVED

PMID: 37115908 (View on PubMed)

Other Identifiers

GH in cirrhosis

Identifier Type: -

Identifier Source: org_study_id