The objective of this study is to investigate whether oral supplementation of citrulline will improve the amount of MSCs and osteogenic capacity in BMAC.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Botaandoeningen. fracturen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The osteogenic potential of MSCs in the BMAC samples.
Secondary outcome
Cell viability and the amount of MSCs
Adverse events
Background summary
Non-union is a common complication after a sustained fracture. The treatment of
a non-union requires a multidisciplinary approach. Not only mechanical
stability and osteoconductive material is needed for an adequate healing
response, also osteogenic cells and osteoinductive reagents are crucial.
Current approaches are aimed towards transposition of osteogenic cells, like
bone marrow aspirate concentrate (BMAC), and the addition of osteoinductive
reagents, like bone morphogenic proteins (BMPs) or collagen. However, it is
known that the nutritional status of a person also has an impact on fracture
healing and the occurrence of non-union. This suggests that improving the
nutritional status of a patient can be a valuable part in non-union treatment.
Some nutrients, like vitamin D and calcium have already been proven to aid in
this process. Non-essential amino acids are described to promote proliferation
and differentiation of mesenchymal stem cells (MSCs), leading to increased
consolidation of fractures. In 2020 the effect of citrulline on fracture
healing was studied in mice and showed an increase in fracture consolidation.
This effect has yet to be studied in human subjects.
When BMAC is used, bone marrow is harvested from the iliac crest of the
patient, centrifuged to isolate the MSCs and growth factors, and then added to
the fracture site. The idea of improving these MSCs before harvesting,
essentially using the body as bioreactor, can be a low-impact and cost
efficient way to improve non-union surgery.
Study objective
The objective of this study is to investigate whether oral supplementation of
citrulline will improve the amount of MSCs and osteogenic capacity in BMAC.
Study design
The study will be performed as a single center randomized open label pilot
study.
Intervention
The control group will receive no supplementation. The two intervention groups
will receive either once or twice 5 grams of oral L-citrulline supplementation
14 days prior to the surgery to remove the OSM. Bone marrow will be harvested
from the iliac crest during surgery and centrifuged to create BMAC.
Study burden and risks
From the study supplement, citrulline, no risks or burden is to be expected.
Persons participating in the study will undergo a bone marrow puncture in the
iliac crest. This procedure will be performed under general or spinal
anesthesia. From this puncture some postoperative pain can be expected, long
term complaints only rarely reported. Complication rates of bone marrow
punctures of the iliac crest are low, up to 0.3% is reported.
P.debyelaan 25
Maastricht 6229 HX
NL
P.debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
- Age >18 years
- Patients are planned for the removal of OSM under general anaesthesia or
spinal anaesthesia where the iliac crest is anesthetized.
Exclusion criteria
- Age <18 years
- Patients with a reported allergy for L-citrulline.
- Chronic use of NSAIDs or use of NSAIDs 14 days prior to surgery
- Chronic use of immunosuppressant medications or use 14 days prior to surgery
- The use of bisphosphonates
- Inability to stop therapeutic anticoagulants prior to surgery
- Surgery under general anaesthesia or spinal block not possible
- Unmanaged comorbidities known to effect bone metabolism: Such as diabetes,
osteoporosis, recent polytrauma
- Subject has (had) an active infection or fever in the weeks prior to the
surgery
- Malnutritional state based on The Simplified Nutritional Appetite
Questionnaire (SNAQ).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84409.068.23 |