Treatment Of Maxillary Bone Cysts With Autologous Bone Mesenchymal Stem Cells (MSV-H) (BIOMAX)

This study is currently recruiting participants.
Verified May 2013 by Red de Terapia Celular
Sponsor:
Collaborators:
Sanidad de Castilla y Leon (SACYL)
University of Valladolid
Centro en Red de Medicina Regenerativa de Castilla y Leon
Information provided by (Responsible Party):
Red de Terapia Celular
ClinicalTrials.gov Identifier:
NCT01389661
First received: July 5, 2011
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

This trial pretends to validate for clinical use a bioengineered product composed of MSV cells (mesenchymal stem cells produced by IBGM, Valladolid, which have already been approved by the Spanish Regulatory Agency for three previous clinical trials) and a cross-linked matrix of autologous plasma patented by The Blood and Tissue Bank of Asturias (WO2008/ 119855) for bone maxillary cysts refilling. These two groups collaborate in the present project with the team of Maxillofacial Surgery of the Hospital Universitario del Río Hortega, who leads the clinical trial and deals with the medical aspects. The proposed trial is based on positive results obtained in previous animal studies performed by the present multidisciplinary team. The investigators propose a phase I / II clinical trial with 10 patients suffering from bone cysts in the maxillofacial region. Autologous mesenchymal stem cells isolated from a bone marrow sample will be seeded in the autologous plasma matrix and cultivated for 3 weeks. At this time, the cyst will be removed by surgery and the cavity filled with the protein matrix containing the mesenchymal cells. Checks will be conducted at 3 weeks, 3 and 6 months following the evolution of the cavity by panoramic radiography and computerized tomography scan.


Condition Intervention Phase
Maxillary Cyst
Bone Loss of Substance
Other: Autologous Mesenchymal Stem Cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Regeneration of Maxillary Bone Cystic Cavities by Bio Implant of MSHV-H Cells Associated to a Cross-linked Serum Scaffold

Further study details as provided by Red de Terapia Celular:

Primary Outcome Measures:
  • To evaluate the feasibility and safety of the implementation of MSV in the treatment of maxillary cysts [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
    Clinical review and orthopantomograpy at different periods (0, 2 weeks, 2 months and 6 months) assessing evolution from baseline and possible complications.


Secondary Outcome Measures:
  • Indication of efficacy [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    Imaging exploration to evaluate effectiveness through development of criteria for orthopantomography and bone-CT quantitative bone regeneration Evolution at 2 and 6 months from intervention will be assessed.


Estimated Enrollment: 10
Study Start Date: April 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSV treatment
MSV-H autologous transplantation. Mesenchymal stem cells from bone marrow expanded by GMP-compliant procedure in IBGM cell production unit in autologous plasma scaffold and implanted in maxillary bone cavities after cyst removal
Other: Autologous Mesenchymal Stem Cells
Autologous maxillary bone marrow mesenchymal stem cells (MSV-H) collected from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV)
Other Name: H-MSV, Human Mesenchymal Stem Cells from Valladolid

Detailed Description:

The objective of this project is to provide a competitive clinical solution with an autologous product, a balanced cost and the possibility of extending use to other pathologies.

This protocol includes treatment of 10 patients with cystic disease of the jaws that meet all the inclusion criteria and none of the exclusion criteria.

For autologous cell preparation a sample of spongy bone from the maxillary tuberosity and 20 ml of serum are obtained from the patient in order to prepare the crosslinked protein matrix and the MSV-H cells. Cells are selected and expanded under GMP conditions according to the methodology used in previous trials (EudraCT 2005-005498-36, 2008-001191-68 and 2009-0170450-11 ). MSV-H cells are obtained directly from biopsy culture jawbone of the patient by cultivation techniques "in vitro" and differentiate for 21 days once conveyed in the matrix with osteogenic differentiation medium of the following composition: DMEM, 10% FBS, 1% P / E, 0.1 mM dexamethasone, 50 mM ascorbate 2-phosphate, 10 mM phosphate ßGlicerol. All differentiation factors have already been approved for clinical use. After the period of the product differentiation can be implanted to the patient.

The bioimplant is used to refill the bone defects after osteotomy and maxillary cyst enucleation, with 5-10 million cells per unit of 2 cm in diameter and 0.3 cm thick. The cavity is closed with the mucoperiosteal flap and sutured with reabsorbable material. The end point of the trial is to evaluate the feasibility, safety and indications of treatment efficacy according to both clinical criteria and objective imaging confirming the volumetric bone regeneration and maintenance over time. For this purposes orthopantomography exploration will be performed before and 2 and 6 months after intervention.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Maxillar bone cyst with diameter larger than 2 cm and smaller than 4 cm
  • Understanding and written acceptance of assay conditions
  • Informed written consent of the patient for assay and for surgery
  • In women, negative pregnancy test at t=0
  • In women, compromise of using anticonceptive methods during the study

Exclusion Criteria:

  • Age under 18 or over 65
  • Incapacity or legal dependence
  • Pregnancy, lactancy, or enrollment in fertility programs
  • Previous or concomitant oncological processes.
  • Positive serology for HIV-1 orHIV-2, Hepatitis B (HBsAg, Anti-HCV-Ab) or Hepatitis C (Anti-HCV-Ab).
  • Immunocompromised patients
  • Systemic disease with potential effects on bone metabolism
  • Congenital or acquired maxillofacial malformation
  • Patients with prescription of drugs acting on bone metabolism, suc as glucocorticoids and bisphosphonates
  • Active or recent infection of the cyst
  • Recidive of the cyst (previous surgery)
  • Participation in other trials or studies in the last 3 months.
  • Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01389661

Contacts
Contact: Luis M Redondo, MD, PhD, PI 0034 983 233850 med020120@gmail.com
Contact: Ana Sánchez, MD, PhD, coPI 0034 983 184121 asanchez@ibgm.uva.es

Locations
Spain
Río Hortega University Hospital Recruiting
Valladolid, Valladid, Spain, 47012
Contact: Luis M Redondo, MD, PhD    0034 983233850    med020120@gmail.com   
Contact: Alberto Verrier, MD, PhD    0034 983349036    averrierh56@hotmail.com   
Principal Investigator: Luis M Redondo, MD, PhD         
Sub-Investigator: Alberto Verrier, MD, PhD         
Sub-Investigator: Javier Fernández, MD         
Sub-Investigator: Rafael Gómez, MD         
Sub-Investigator: Rebeca Pintado, MD         
Sub-Investigator: Maria Villacastín, MD         
Instituto de Biologia y Genetica Molecular Recruiting
Valladolid, Spain, 47003
Contact: Ana Sánchez, MD, PhD    0034 983 184830    asanchez@ibgm.uva.es   
Contact: Javier García-Sancho, MD, PhD    0034 983 423084    jgsancho@ibgm.uva.es   
Principal Investigator: Ana Sánchez, MD, PhD         
Principal Investigator: Javier García-Sancho, MD, PhD         
Sub-Investigator: Veronica Garcia, MsC         
Sponsors and Collaborators
Red de Terapia Celular
Sanidad de Castilla y Leon (SACYL)
University of Valladolid
Centro en Red de Medicina Regenerativa de Castilla y Leon
Investigators
Principal Investigator: Luis M Redondo, MD, PhD Oral and Maxillofacial Surgeon, Río Hortega University Hospital, SACYL, Valladolid, Spain
Study Director: Ana Sánchez, MD, PhD Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, Spain
Study Director: Javier García-Sancho, MD, PhD University of Valladolid, Spain
  More Information

Additional Information:
No publications provided

Responsible Party: Red de Terapia Celular
ClinicalTrials.gov Identifier: NCT01389661     History of Changes
Other Study ID Numbers: TerCel0002, 2010-024246-30, EC10-255, BIOMAX-VA-2010
Study First Received: July 5, 2011
Last Updated: May 21, 2013
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ministry of Health and Consumption

Keywords provided by Red de Terapia Celular:
Maxillary bone cysts
Cell therapy
Mesenchymal stem cells
Autologous serum scaffold

Additional relevant MeSH terms:
Cysts
Neoplasms
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on April 22, 2014