Contact information
Type
Scientific
Primary contact
Dr Laurent Spahr
ORCID ID
Contact details
Gastroenterology and Hepatology
University Hospital of Geneva
24
Rue Micheli-du-Crest
Geneva
CH-1211
Switzerland
+41 22 372 93 40
Laurent.Spahr@hcuge.ch
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Swissmedic 2005DR2212
Study information
Scientific title
Granulocyte colony-stimulating factor (G-CSF) induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial
Acronym
Study hypothesis
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
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)
Study design
Single-center randomized controlled pilot trial (not blinded).
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
Primary outcome measures
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 trial start date
01/09/2005
Overall trial end date
31/08/2006
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
24
Participant 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
Recruitment start date
01/09/2005
Recruitment end date
31/08/2006
Locations
Countries of recruitment
Switzerland
Trial participating centre
Gastroenterology and Hepatology
Geneva
CH-1211
Switzerland
Funders
Funder type
Other
Funder name
Foundation for Liver and Gut Studies (FLAGS), a non profit organisation based in Geneva (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
University Hospital of Geneva (Hôpitaux Universaires de Genève; HUG) (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary