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02 September 2010
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| [ Print-friendly version ] |
| Granulocyte colony-stimulating factor (G-CSF) and liver regeneration in patients with alcoholic steatohepatitis |
| ISRCTN | ISRCTN86571875 |
| ClinicalTrials.gov identifier | |
| Public title | Granulocyte colony-stimulating factor (G-CSF) and liver regeneration in patients with alcoholic steatohepatitis |
| Scientific title | Granulocyte colony-stimulating factor (G-CSF) induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial |
| Acronym | N/A |
| Serial number at source | Swissmedic 2005DR2212 |
| 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). |
| Countries of recruitment | Switzerland |
| Disease/condition/study domain | Alcoholic steatohepatitis |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/09/2005 |
| Anticipated end date | 31/08/2006 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 24 |
| Interventions |
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 |
| Primary outcome measure(s) | Ability of G-CSF to increase circulating CD34 + cells (see Interventions for timepoints of assessment) |
| Secondary outcome measure(s) |
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 |
| Sources of funding |
1. Foundation for Liver and Gut Studies (FLAGS), a non profit organisation based in Geneva (Switzerland)
2. University Hospital of Geneva (Hôpitaux Universaires de Genève; HUG) (Switzerland) |
| Trial website | |
| Publications | |
| Contact name | Dr Laurent Spahr |
| Address |
Gastroenterology and Hepatology
University Hospital of Geneva 24, Rue Micheli-du-Crest |
| City/town | Geneva |
| Zip/Postcode | CH-1211 |
| Country | Switzerland |
| Tel | +41 22 372 93 40 |
| Fax | +41 22 372 93 66 |
| Laurent.Spahr@hcuge.ch | |
| Sponsor | Foundation for Liver and Gut Studies (FLAGS) (Switzerland) |
| Address | 12, Rue Adrien Lachenal |
| City/town | Geneva |
| Zip/Postcode | CH-1207 |
| Country | Switzerland |
| Date applied | 28/02/2008 |
| Last edited | 14/03/2008 |
| Date ISRCTN assigned | 14/03/2008 |
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