Growth Hormone Therapy in Liver Cirrhosis

NCT03420144 | Completed Phase 2

• 1 other identifier: GH in cirrhosis
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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

Keywords

Growth hormone; cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Improvement in BMI

  One Year

• Improvement in Mid arm muscle circumference(MAMC)

  One year

• Improvement in hand grip strength

  One year

• Clinical improvement in liver function

  One Year

• Biochemical improvement in liver function

  One year

Study Arms (2)

Standard Medical Therapy

ACTIVE COMPARATOR

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

Drug: Standard Medical Therapy

Growth hormone

ACTIVE COMPARATOR

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; Drug: Growth Hormone

Interventions

Standard Medical Therapy DRUG

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

Growth hormone; Standard Medical Therapy

Growth Hormone 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.

Growth hormone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Decompensated Cirrhosis of liver irrespective of etiology

You may not qualify if:

• 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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Related Publications (1)

• 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.

  PMID: 37115908 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis

Interventions

Growth Hormone

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Hepatology

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 5, 2018
• Study Start: January 15, 2018
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: May 3, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)