Cirrhosis, LiverPhase 2/3NCT03415698
G-CSF in Decompensated Cirrhosis: an Open Label Trial
A Phase 2/3 study testing G-CSF and Standard Medical Therapy in people with Cirrhosis, Liver, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is typified by an initial, largely asymptomatic, "compensated" phase followed by "decompensation" due to complications of raised portal pressures and hepatocellular dysfunction. 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?
- G-CSF and Standard Medical Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2016to Dec 2018
- 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
Show all 14Show fewer
- 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 G-CSF
- HIV co-infection
- Pregnancy
- Refusal to give informed consent
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
Virendra Singh, DM, 7087009338, virendrasingh100@hotmail.com
Arka De, MD, 9999816539, arkascore@gmail.com
About this study
Official title: Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study
Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is typified by an initial, largely asymptomatic, "compensated" phase followed by "decompensation" due to complications of raised portal pressures and hepatocellular dysfunction.
Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage, exorbitant costs and lack of widespread availability. The need for long term immunosuppression and its attendant complications are a further drawback. The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that they can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed. Bone marrow derived stem cells have amazing plasticity. They can "home" to the liver in response to injury and help in liver regeneration by trans-differentiation, cell fusion and augmentation of tissue- resident stem cell mediated repair. Two methods are available for the mobilisation of stem cells from the bone marrow to the liver. One involves the administration of cytokines like granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells from the marrow followed by their injection into the hepatic artery or portal vein after purification. The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients .
Read more
G-CSF has been shown to mobilise bone marrow stem cells and even increase survival in patients of severe alcoholic steatohepatitis and ACLF. There is conflicting evidence on the role of G-CSF in decompensated cirrhosis with some studies showing improved survival while others have shown a lack of clinical or biochemical benefit. Many of these studies have used a single course of G-CSF. Verma et al, in a recent study published in 2018, elegantly demonstrated the beneficial effect of multiple courses of G-CSF in improving mortality and transplant free survival in decompensated cirrhotics.
The investigators too speculate that multiple cycles of G-CSF could result in better outcomes in decompensated cirrhosis by causing more prolonged and sustained stem cell homing to the liver. Thus, this study is being undertaken to further evaluate the safety and efficacy of multiple cycles of G-CSF in decompensated cirrhotics.
- Conditions
- Cirrhosis, Liver
- Being tested
- G-CSF, Standard Medical Therapy
- Keywords
- Regenerative medicine
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFDrug
G-CSF will be administered at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days. four such cycles will be administered at three monthly intervals.
Standard Medical TherapyDrug
Nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics.
| Study group | Role | What they receive |
|---|---|---|
| Standard Medical Therapy | Active comparator | Standard medical therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins, antibiotics. fresh frozen plasma and packed red-cell transfusions (as required) Receives: Drug: Standard Medical Therapy |
| G-CSF + Standard Medical Therapy | Active comparator | G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr will be administered for five consecutive days. Four such cycles at 3 monthly intervals will be administered. Receives: Drug: G-CSF; Drug: Standard Medical Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Survival at 1 year after start of therapy
Measured: One year
Secondary outcomes (6)
Hemopoieticstem cell mobilisation
Mobilisation of CD 34+ cells in peripheral blood
Measured: One Year
Clinical improvement in liver functions
Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed
Measured: One Year
Biochemical improvement in liver functions
Improvment in MELD score
Measured: One year
Improvement in nutritional status
Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level
Measured: One Year
Improvement in quality of life
Quality of life will be assessed using SF-36V2 Health Survey questionnaire
Measured: One year
Safety of G-CSF as assessed by its adverse effects
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 posted30 Jan 2018
- Study startJul 2016
- Primary completionJul 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- 100 participants (estimated)
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
- Investigators
- Virendra Singh, DM, Principal investigator, Professor, Department of Hepatology, PGIMER, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03415698
- Sponsor's protocol ID
- GCSF in cirrhosis
- Status last verified
- Jan 2018
- First submitted
- 11 Jan 2018
- Last updated
- 30 Jan 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kaur A, Verma N, Singh B, Kumar A, Kumari S, De A, Sharma RR, Singh V. Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis. Front Med (Lausanne). 2023 Mar 22;10:1118531. doi: 10.3389/fmed.2023.1118531. eCollection 2023.
PubMed 37035316De A, Kumari S, Singh A, Kaur A, Sharma R, Bhalla A, Sharma N, Kalra N, Singh V. Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Feb;19(2):375-383.e5. doi: 10.1016/j.cgh.2020.02.022. Epub 2020 Feb 21.
PubMed 32088302
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study
- ClinicalTrials.gov ID
- NCT03415698
- Acronym / sponsor ID
- GCSF in cirrhosis
- Conditions
- Cirrhosis, Liver
- Keywords
- Regenerative medicine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 30 Jan 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.
Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is typified by an initial, largely asymptomatic, "compensated" phase followed by "decompensation" due to complications of raised portal pressures and hepatocellular dysfunction.
Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage, exorbitant costs and lack of widespread availability. The need for long term immunosuppression and its attendant complications are a further drawback. The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that they can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed. Bone marrow derived stem cells have amazing plasticity. They can "home" to the liver in response to injury and help in liver regeneration by trans-differentiation, cell fusion and augmentation of tissue- resident stem cell mediated repair. Two methods are available for the mobilisation of stem cells from the bone marrow to the liver. One involves the administration of cytokines like granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells from the marrow followed by their injection into the hepatic artery or portal vein after purification. The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients .
G-CSF has been shown to mobilise bone marrow stem cells and even increase survival in patients of severe alcoholic steatohepatitis and ACLF. There is conflicting evidence on the role of G-CSF in decompensated cirrhosis with some studies showing improved survival while others have shown a lack of clinical or biochemical benefit. Many of these studies have used a single course of G-CSF. Verma et al, in a recent study published in 2018, elegantly demonstrated the beneficial effect of multiple courses of G-CSF in improving mortality and transplant free survival in decompensated cirrhotics.
The investigators too speculate that multiple cycles of G-CSF could result in better outcomes in decompensated cirrhosis by causing more prolonged and sustained stem cell homing to the liver. Thus, this study is being undertaken to further evaluate the safety and efficacy of multiple cycles of G-CSF in decompensated cirrhotics.
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 will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins, antibiotics. fresh frozen plasma and packed red-cell transfusions (as required) |
| G-CSF + Standard Medical Therapy | Active comparator | Drug: G-CSF, Drug: Standard Medical TherapyG-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr will be administered for five consecutive days. Four such cycles at 3 monthly intervals will be administered. |
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 |
|---|---|---|
| G-CSFG-CSF will be administered at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days. four such cycles will be administered at three monthly intervals. | Drug | G-CSF + Standard Medical Therapy |
| Standard Medical TherapyNutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics. | Drug | G-CSF + Standard Medical Therapy, Standard Medical Therapy |
Primary outcome
Survival
Time frame: One year
Survival at 1 year after start of therapy
6 secondary outcomes
Hemopoieticstem cell mobilisation
Time frame: One Year
Clinical improvement in liver functions
Time frame: One Year
Biochemical improvement in liver functions
Time frame: One year
Improvement in nutritional status
Time frame: One Year
Improvement in quality of life
Time frame: One year
Safety of G-CSF as assessed by its adverse effects
Time frame: One Year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2018.
- Derived from this study: PubMed 37035316Kaur A, Verma N, Singh B, Kumar A, Kumari S, De A, Sharma RR, Singh V. Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis. Front Med (Lausanne). 2023 Mar 22;10:1118531. doi: 10.3389/fmed.2023.1118531. eCollection 2023.
- Derived from this study: PubMed 32088302De A, Kumari S, Singh A, Kaur A, Sharma R, Bhalla A, Sharma N, Kalra N, Singh V. Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Feb;19(2):375-383.e5. doi: 10.1016/j.cgh.2020.02.022. Epub 2020 Feb 21.
- 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.
Virendra Singh, DM principal investigator
Professor, Department of Hepatology, PGIMER, Chandigarh
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 G-CSF and Standard Medical Therapy 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: status not confirmed, as of the sponsor's last update on 30 Jan 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Virendra Singh, DM (7087009338, virendrasingh100@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (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 NCT03415698, which also lists 2 linked publications.
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 30 Jan 2018.