Condition category
Nutritional, Metabolic, Endocrine
Date applied
28/02/2008
Date assigned
14/03/2008
Last edited
14/03/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

Sponsor information

Organisation

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

Sponsor details

12
Rue Adrien Lachenal
Geneva
CH-1207
Switzerland

Sponsor type

Other

Website

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

Publication citations

Additional files

Editorial Notes