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Growth Hormone Therapy in Liver Cirrhosis

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ClinicalTrials.gov Identifier: NCT03420144
Recruitment Status : Recruiting
First Posted : February 2, 2018
Last Update Posted : February 2, 2018
Sponsor:
Information provided by (Responsible Party):
Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research

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.


Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Drug: Standard Medical Therapy Drug: Growth Hormone Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Growth Hormone Therapy and Its Effect on Nitrogen Metabolism and Malnutrition in Liver Cirrhosis
Actual Study Start Date : January 15, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis Hormones

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.




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03420144


Contacts
Contact: Virendra Singh, DM 7087009338 virendrasingh100@hotmail.com
Contact: Sunita Kumari, M.Tech 9413601016 sunita.karwasra90@gmail.com

Locations
India
Post Graduate Institute of Medical Education and Research Recruiting
Chandigarh, India, 160012
Contact: Virendra Singh, DM    7087009338    virendrasingh100@hotmail.com   
Contact: Sunita Kumari, M.Tech    9413601016    sunita.karwasra90@gmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research

Responsible Party: Dr.Virendra Singh, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03420144     History of Changes
Other Study ID Numbers: GH in cirrhosis
First Posted: February 2, 2018    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research:
Growth hormone
cirrhosis

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs