Cirrhosis, LiverPhase 2/3NCT03420144
Growth Hormone Therapy in Liver Cirrhosis
A Phase 2/3 study testing Standard Medical Therapy and Growth Hormone in people with Cirrhosis, Liver, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cirrhosis, Liver
- What is being tested?
- Standard Medical Therapy and Growth Hormone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteIndia
- Study dates
- 15 Jan 2018to 30 Jun 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Decompensated Cirrhosis of liver irrespective of etiology
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
India1 site
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
About this study
Official title: Growth Hormone Therapy and Its Effect on Nitrogen Metabolism and Malnutrition 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.
Read more
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
- Being tested
- Standard Medical Therapy, Growth Hormone
- Keywords
- Growth hormone, cirrhosis
- Medical subject headings
- Liver Cirrhosis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Medical TherapyDrug
Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required
Growth HormoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard Medical Therapy | Active comparator | Standard medical therapy: diuretics, lactulose, rifaximin, diuretics, albumin infusion, nutritional support (as required) Receives: 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. Receives: Drug: Standard Medical Therapy; Drug: Growth Hormone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: One year
Secondary outcomes (7)
Improvement in BMI
Measured: One Year
Improvement in Mid arm muscle circumference(MAMC)
Measured: One year
Improvement in hand grip strength
Hand grip strength will be measured with the hydraulic hand dyanamometer in Kg/force.
Measured: One year
Clinical improvement in liver function
Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed
Measured: One Year
Biochemical improvement in liver function
Improvment in MELD score
Measured: One year
Improvement in Quality of life
Quality of life will be assessed using SF-36V2 Health Survey questionnaire
Measured: One Year
Improvement in liver regeneration
By measuring hepatic parenchymal cell specific marker (CD 133) and cell proliferation marker (Ki-67) by immunohistochemistry.
Measured: One Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start15 Jan 2018
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cirrhosis, LiverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr.Virendra Singh, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03420144
- Sponsor's protocol ID
- GH in cirrhosis
- Status last verified
- Apr 2023
- First submitted
- 11 Jan 2018
- Last updated
- 3 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37115908
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Growth Hormone Therapy and Its Effect on Nitrogen Metabolism and Malnutrition in Liver Cirrhosis
- ClinicalTrials.gov ID
- NCT03420144
- Acronym / sponsor ID
- GH in cirrhosis
- Conditions
- Cirrhosis, Liver
- Keywords
- Growth hormone, cirrhosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Medical Therapy | Active comparator | Drug: Standard Medical TherapyStandard medical therapy: diuretics, lactulose, rifaximin, diuretics, albumin infusion, nutritional support (as required) |
| Growth hormone | Active comparator | Drug: Standard Medical Therapy, Drug: Growth HormoneGrowth 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Decompensated Cirrhosis of liver irrespective of etiology
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Medical TherapyStandard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required | Drug | Growth hormone, Standard Medical Therapy |
| Growth HormoneGH 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. | Drug | Growth hormone |
Primary outcome
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
7 secondary outcomes
Improvement in BMI
Time frame: One Year
Improvement in Mid arm muscle circumference(MAMC)
Time frame: One year
Improvement in hand grip strength
Time frame: One year
Clinical improvement in liver function
Time frame: One Year
Biochemical improvement in liver function
Time frame: One year
Improvement in Quality of life
Time frame: One Year
Improvement in liver regeneration
Time frame: One Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Derived from this study: PubMed 37115908Kumari 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Standard Medical Therapy and Growth Hormone in people with Cirrhosis, Liver, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Nutritional status based on CT L3 SMI score. (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03420144, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.