Marrow stem cell therapy to improve liver function in alcoholic liver disease

ISRCTN	ISRCTN83972743
DOI	https://doi.org/10.1186/ISRCTN83972743
Protocol serial number	Swissmedic 2008DR2031
Sponsor	Foundation for Liver and Gut Studies (FLAGS) (Switzerland)
Funders	Foundation for Liver and Gut Studies (FLAGS), a non profit organisation based in Geneva (Switzerland), University Hospital of Geneva (Hôpitaux Universaires de Genève; HUG) (Switzerland)

Submission date: 29/02/2008
Registration date: 10/03/2008
Last edited: 05/07/2013

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

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

Primary study design	Interventional
Study design	Single-center randomized controlled study, not blinded.
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study objectives	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(s)	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.
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	granulocyte colony-stimulating factor (G-CSF)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	31/12/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	All
Target sample size at registration	60
Key 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
Key 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
Date of first enrolment	01/03/2008
Date of final enrolment	31/12/2010

Locations

Countries of recruitment

Switzerland

Study participating centre

University Hospital of Geneva

Geneva
CH-1211
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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	01/12/2013		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes