Contact information
Type
Scientific
Primary contact
Dr Laurent Spahr
ORCID ID
Contact details
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 2008DR2031
Study information
Scientific title
Autologous human bone marrow stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) to improve liver function in patients with decompensated alcoholic liver disease: a randomized study
Acronym
Study hypothesis
Patients with advanced alcoholic liver disease often come to medical attention due to hepatic decompensation (fatigue, jaundice, ascites, bleeding and hepatic encephalopathy). The prognosis depends on the severity of the liver insufficiency. The characteristic features of patients who do not survive is profound liver failure and inability to achieve efficient parenchymal regeneration.
Study hypothesis:
The combination of stimulating autologous hematopoietic stem cells from the bone marrow after a 5-day mobilization course with G-CSF followed by a direct administration into the liver parenchyma via the hepatic artery translates into a better outcome during follow-up as compared to the standard care (which included only supportive measures).
Please note that as of 04/01/10 the anticipated end date for this trial has been extended from 31/03/10 to 31/12/10.
Ethics approval
Protocol N°07-145 approved by the local Ethics Committee (Comite Departemental D'Ethique de Médecine Interne et Médecine Communautaire, 24, Rue Micheli-du-Crest CH-1211 Geneve Switzerland) on November 6, 2007. Also approved by the national Swiss Agency for Therapeutic Products (2008DR2031) on February 7, 2008.
Study design
Single-center randomized controlled study, not blinded.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Alcoholic liver disease
Intervention
The participants will be randomly allocated to the two study arms in equal numbers by an independent person using the sealed envelope technique.
Intervention arm: Stem cell embolisation in the hepatic artery
Control arm: supportive measures only
The following tests will be carried out in both arms at baseline:
1. Liver biopsy
2. Computed tomography (CT) with volumetry
3. Physical examination
4. Blood sampling for cytokines (tumor necrosis factor [TNF], Interleukin-6 [IL6], alpha-fetoprotein [AFP], Hepatocyte Growth Factor [HGF], transforming growth factor [TGF]-beta)
5. Routine hematology and coagulation studies
6. Blood chemistry with liver function test (to measure the MELD score)
Control arm: Supportive measures according to the standard care.
The following will be carried out at Day 28 visit:
1. Repeat liver biopsy
2. Physical examination
3. CT with volumetry
4. Blood sampling (idem)
Day 60 and day 90 visits will include only physical examination and blood tests.
In the treatment arm: Five-day mobilization course with lenograstim (G-CSF) 10 mcg/kg subcutaneously per day, followed by a 40 to 60 ml bone marrow aspiration from the iliac crest. Then, CD34+ and mesenchymal cells will be isolated from the aspirate using a classical Ficoll density separation. Within 36 h of aspiration, the suspension of cells (an average of 0.5 x 10^8 cells) will be selectively embolized via arteriography into the right and left hepatic artery branches, so as to distribute CD34+ and mesenchymal cells in both lobes of the liver. Day 28, 60 and 90 visits will be similar to the control arm.
Intervention type
Drug
Phase
Not Specified
Drug names
granulocyte colony-stimulating factor (G-CSF)
Primary outcome measures
Improvement of liver function, as assessed by a decrease in the MELD score of >3 between baseline, Day 28, 60, and 90 follow-up visits.
Secondary outcome measures
1. Improvement in liver function as assessed by the following parameters at Day 28, 60, and 90:
1.1. Bilirubin
1.2. Albumin
1.3. Coagulation times
1.4. Presence or absence of ascites
1.5. Presence or absence of hepatic encephalopathy)
This will allow the calculation of the Child-Pugh's score
2. Mortality at 3 and 6 months
3. Evolution of serum markers of liver regeneration (AFP, HGF), inflammation (TNF, IL6) and fibrosis (TGF-beta)
4. Changes in liver histology at Day 28
Overall trial start date
01/03/2008
Overall trial end date
31/12/2010
Reason abandoned
Eligibility
Participant inclusion criteria
1. Age 18-75 years
2. Biopsy-proven alcoholic liver disease
3. Abnormal liver function with a Model for End-Stage Liver Disease (MELD) (assessment that include bilirubin, coagulation time and creatinine) score 10-26
4. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
60
Participant exclusion criteria
1. Recent (10 days) infection or hemorrhage
2. Estimated survival <6 months
3. Coexistent HIV, hepatitis C virus (HCV), hepatitis B virus (HBV)
4. Portal vein obstruction
5. Documented hepatocellular carcinoma
6. Severe liver atrophy as defined by volumetry <0.6% body weight
7. Leucocytes >25g/L
8. Known hypersensitivity to G-CSF
9. Creatinine >150 µmol/L
10. Contraindication to arteriography
11. Clinically overt hepatic encephalopathy
12. Absence of written consent
Recruitment start date
01/03/2008
Recruitment end date
31/12/2010
Locations
Countries of recruitment
Switzerland
Trial participating centre
University Hospital of Geneva
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
1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23341981
Publication citations
-
Results
Spahr L, Chalandon Y, Terraz S, Kindler V, Rubbia-Brandt L, Frossard JL, Breguet R, Lanthier N, Farina A, Passweg J, Becker CD, Hadengue A, Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial., PLoS ONE, 2013, 8, 1, e53719, doi: 10.1371/journal.pone.0053719.