Granulocyte colony-stimulating factor (G-CSF) and liver regeneration in patients with alcoholic steatohepatitis

ISRCTN	ISRCTN86571875
DOI	https://doi.org/10.1186/ISRCTN86571875
Secondary identifying numbers	Swissmedic 2005DR2212

Submission date: 28/02/2008
Registration date: 14/03/2008
Last edited: 30/12/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Laurent Spahr
Scientific

Gastroenterology and Hepatology
University Hospital of Geneva
24, Rue Micheli-du-Crest
Geneva
CH-1211
Switzerland

Phone	+41 22 372 93 40
Email	Laurent.Spahr@hcuge.ch

Study information

Study design	Single-center randomized controlled pilot trial (not blinded).
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title	Granulocyte colony-stimulating factor (G-CSF) induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial
Study objectives	Liver failure is a major cause of death in patients with alcoholic steatohepatitis. Many patients are not candidates for liver transplantation, and no therapy has proven useful to promote liver regeneration. Granulocyte colony stimulating factor (G-CSF) showed promising results in ischemic heart disease in the repopulation of the parenchyma by pluripotent cells issued from the bone marrow following a mobilization course by G-CSF. Hypothesis: The effects of a 5-day course of G-CSF in patients with alcoholic steatohepatitis associated with cirrhosis is well tolerated and is associated with signs of liver cell proliferation in the short-term.
Ethics approval(s)	Protocol N°05-089 approved by the local Ethics Committee of the University Hospital of Geneva (Hôpitaux Universitaires de Genève, Comite Departemental d'Ethique de Medecine Interne et Medecine Communautaire, 24, Rue Micheli-du-Crest, CH-1211 Genève, Switzerland). Date of approval: 14/06/2005 This study was also approved by the Swiss Agency for therapeutic products (Swissmedic)(ref: 2005DR2212)
Health condition(s) or problem(s) studied	Alcoholic steatohepatitis
Intervention	Thirteen patients were randomized to standard care + G-CSF, and 11 patients to standard care only. The random allocation of participants to the two arms of the study were carried out using the sealed envelope technique by an independent nurse. Baseline assessments (both intervention and control arms): 1. Patients had a transjugular liver biopsy as part of the diagnostic work-up of decompensated alcoholic liver disease. 2. Physical examination, blood sampling for routine values (coagulation, blood chemistry and liver function tests) and cytokines measurements: alfa-foetoprotein (AFP), hepatocyte growth factor (HGF) 3. Measurement of CD34+ hematopoietic stem cells (flow cytometry) 4. Aminopyrine breath test (microsomal liver function) 5. Immunohistochemistry for CK7 and Ki67 (identification of hepatic progenitor cells with proliferative activity) Patients randomized to G-CSF: Mobilization course by G-CSF (10 mcg/kg/day) for 5 days. Assessments for both arms at day 7: 1. Repeat liver biopsy with similar immunohistochemistry studies 2. Physical examination 3. Repeat routine blood tests and cytokines 4. Measurement of CD34+ hematopoietic stem cells (flow cytometry) 5. Aminopyrine breath test Assessments for both arms at day 28 visit: 1. Physical examination 2. Routine blood tests and cytokines Both arms at day 90: Clinical outcome
Intervention type	Other
Primary outcome measure	Ability of G-CSF to increase circulating CD34 + cells (see Interventions for timepoints of assessment)
Secondary outcome measures	1. Safety of filgrastim in patients with liver failure 2. Effects of filgrastim on liver regeneration assessed using biological markers and immunohistochemistry 3. Possible influence of filgrastim on liver function See Interventions for details of assessments
Overall study start date	01/09/2005
Completion date	31/08/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	70 Years
Sex	Both
Target number of participants	24
Total final enrolment	24
Key inclusion criteria	1. Age 18-70 years 2. Recent heavy alcohol intake (>80 g/day) 3. Biopsy-proven alcoholic steatohepatitis 4. Maddrey's score >20 and <70 5. Leucocyte count <15 g/L 6. Ability to give an informed consent
Key exclusion criteria	1. Platelet count <20 g/L 2. International Normalised Ratio (INR) >1.9 3. Known hypersensitivity to filgrastim (G-CSF) 4. Creatinine >150 µmol/L 5. Recent (10 days) infection or gastrointestinal hemorrhage 5. Documented hepatocellular carcinoma, hepatitis B, C, or HIV seropositivity 6. Ongoing pregnancy
Date of first enrolment	01/09/2005
Date of final enrolment	31/08/2006

Locations

Countries of recruitment

Switzerland

Study participating centre

Gastroenterology and Hepatology

Geneva
CH-1211
Switzerland

Sponsor information

Foundation for Liver and Gut Studies (FLAGS) (Switzerland)
Other

12, Rue Adrien Lachenal
Geneva
CH-1207
Switzerland

Funders

Funder type

Other

Foundation for Liver and Gut Studies (FLAGS), a non profit organisation based in Geneva (Switzerland)

No information available

University Hospital of Geneva (Hôpitaux Universaires de Genève; HUG) (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2008	30/12/2020	Yes	No

Editorial Notes

30/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.