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NCT Number: NCT03420144

Growth Hormone Therapy 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.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Standard Medical Therapy

Drug

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

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.

Primary outcomes

  1. Improvement in Nutritional status based on CT L3 SMI score.

    Time frame: One year

    Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level

Secondary outcomes

  1. Improvement in BMI

    Time frame: One Year

  2. Improvement in Mid arm muscle circumference(MAMC)

    Time frame: One year

  3. Improvement in hand grip strength

    Time frame: One year

    Hand grip strength will be measured with the hydraulic hand dyanamometer in Kg/force.

  4. Clinical improvement in liver function

    Time frame: One Year

    Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed

  5. Biochemical improvement in liver function

    Time frame: One year

    Improvment in MELD score

  6. Improvement in Quality of life

    Time frame: One Year

    Quality of life will be assessed using SF-36V2 Health Survey questionnaire

  7. Improvement in liver regeneration

    Time frame: One Year

    By measuring hepatic parenchymal cell specific marker (CD 133) and cell proliferation marker (Ki-67) by immunohistochemistry.

Sponsors and collaborators

Lead sponsor

Post Graduate Institute of Medical Education and Research, Chandigarh

Other

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Feb 5, 2018
Registry last updated
May 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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