Non Union Fracture Clinical Trial
Official title:
Potency of Allogenic Bone Marrow, Umbilical Cord, Adipose Mesenchymal Stem Cell for Non Union Fracture and Long Bone Defect, Directly and Cryopreserved
Mesenchymal stem cell (MSC) is one kind of stem cell which is gained form adult tissue.
Although MSC derived from autogenic bone marrow are proven to help regeneration in non union
fracture and long bone defect, the aspiration process through iliac crest is invasive and
painful.
Therefore, alternative source of MSC which is less invasive is needed. Adipose and umbilical
cord is a "waste product" that proven to contain enormous MSC. Furthermore adipose and
umbilical cord as an allogenic source is more abundant in number compares to autogenic bone
marrow. This enormous source need and adequate preservation technique before applied to the
patient. According to that, researchers want to explore the potency of MSC from bone marrow,
umbilical cord and adipose as the source of allogenic MSC and the effect of cryopreservation
technique to the viability and quality of MSC. We will also compare the effectivity of MSC
implantation from bone marrow, umbilical cord and adipose applied to non union fracture and
long bone defect.
Samples from bone marrow, umbilical cord and adipose are cultured and the viability of the
cells are observed. Some of the cells are implanted directly to the patient with non union
fractures and long bone defect while some are cryopreserved in liquid nitrogen -190 degree
Celsius in three months. All samples are thawed and the viability of the cells are observed.
Patient who are implanted by MSC allogenic will undergo clinical and radiological
examination in the third, sixth and twenty second month after implantation.
Research Methods Study Design This study is an experimental one arm study post test only.
Estimated Study Time Research estimated time would be 24 months, from May 2014 to May 2016.
Sample Gaining Procedure This research is a pilot study. Samples are obtained consecutively
from all source population that meet the criteria. The number of samples from each
mesenchymal stem cell ( adipose, bone marrow and umbilical cord) source are three. Each
samples derived from three different donors that met the inclusion criteria. For the
implanation, the subjects are five from each intervention. Yet regarding the limited funding
source and time, we will recruit one subject for each kind of MSC.
Subject Criteria Inclusion criteria for MSC donor
Bone marrow donor :
Male/female aged 19-30 year without any comorbiditites (Diabetes mellitus, cardiovascular
and any other autoimmune disease), HIV test Hepatitis B test and Hepatitis C test are
negaitve, no fungal and bacterial contamination in the bone marrow. Subjects are willing to
be aspiratied in the iliac crest in order to get the bone marrow.
Adipose donor :
Adipose tissue are gained from liposuction or open reduction internal fixation procedure.
Samples of adipose are free from HIV, Hepatitis B, Hepatitis C and free from fungal and
bacterial contamination.
Umbilical cord donor :
Umbilical cord are form elective seccio caecaria from a fullterm mother without any
complications and free from HIV, hepatitis B, hepatitis C and no fungal and bacterial
contamination.
Recipient inclusion criteria Critical bone defect patients aged 6-55 who are willing to
undergo surgical intervention.
Recipient exclusion criteria Patients with pathological fracture caused by malignancy,
immunocompromised ( HIV AIDS, Diabetes mellitus, active Hepatitis), in a immunosuppresant
therapy ( chemotherapy or steroids).
Drop out criteria Patients are ruled out from this study if he/she stated to do so in the
time this research are held or she/he undergoes any other threatment that are not related to
this study. Patient who does not show any clinical improvement in three consecutive months
is categorized as failed to threat. All drop out and failed to threat patient could get
other threatment.
Informed Consent All subjects must fill and sign in the informed consent letters.
Research Protocol Mesenchymal stem cell taking method Bone Marrow taking Patient is lying
down in supine position, anesthetized locally. Aseptic and antiseptic are done in the illiac
crest location. Aspiration needle is inserted 450 to horizon in illiac crest. Hub is
released and a 10 cc syringe that contain heparin is connected to te needle. We aspirated
about 50 cc bone marrow from each subject.
Umbilical cord taking Right after the delivering the baby, the umbilical cord are cut and
kept in a sterile bowl containing 0.9% NaCl in 40 until the sample is proceed.
Adipose taking Adipose tissue are derived from liposuction or open reduction internal
fixation procedure. It is kept in a sterile bowl containing NaCL 0.9% in 40 C. Processing of
the sample is done within 8 hours after sample are taken.
Cryopreservation and re activation. All the samples are taken to culture laboratory in
integrated service of stem cell medical technology Cipto mangunkusumo hospita.this
laboratory is GMP (good manufacturing Product) certified. The samples ate cultured in
appropriated medium until it reach confluence and harvested. The cells then undergo
caracterisation test by flow cyto meter and viability and numbers are counted. Some of the
cells then cryopreserved while some are directly implanted into patient. The cells are
cryopreserved for three months and then reactivated. Viability and numbers then are
measured. The cells then are implanted to non union patient.
Specimen sterility Sterility tests are done three times to ensure there is no fungal and
bacterial contamination.
HA-CaSO4 and MSC For every centimeter of defect, 10 millions cells and 50 pellet HA-CaSO4
are needed. The diluted MSC then mix with the HA-CaSO4 and incubated 5 minutes before
implanted.
Intervention Surgical intervention is needed to assemble the fixation device in the long
bone. During the surgery, pellet HA-CaSO4 are inserted into the defect. After soft tissue
are closed the rest of the serum is injected into the defect area.
Observation and follow up Clinical and radiological follow up is done every 4 weeks.
Observation is done for 12 months or untill the bone unites. Every subject will be followed
up in the third, sixth, twelfth and twenty forth or until the fixation device is taken off.
Recipient criteria for non union fracture
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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