Bone InjuryNCT05792371
The Role of Type H Vessel Formation in Induced Membrane of Patients With Critical Size Bone Defect
A study testing induced membrane technique and Bone graft (Stage II of IMT) in people with Bone Injury, run by Chang Gung Memorial Hospital.
Trial summary
The goal of this clinical trial is to test the role of type H vessel and investigate the mechanism of its regulation in induced membrane created by induced membrane technique in patients with open fracture, aged between 20 and 80. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Bone Injury
- What is being tested?
- induced membrane technique and Bone graft (Stage II of IMT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2023to 2 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Accept the informed consent form
- Age: 20 years to 80 years
- Type II and III open fracture with 2-6.5 cm defect size
Who cannot join
- Not accept the informed consent form
- Age smaller than 20 years and over 80 years
- Quit during the trial
- patients with Notifiable infectious diseases such as AIDS and hepatitis as well as cancer
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Role of Endothelial Cell-mediated Type H Vessel Formation in Induced Membrane-enhanced Bone Union of Patients With Critical Size Bone Defect
The goal of this clinical trial is to test the role of type H vessel and investigate the mechanism of its regulation in induced membrane created by induced membrane technique in patients with open fracture, aged between 20 and 80.
The main questions to answer are:
Read more
- Whether type H vessel will be critical for induced membrane-mediated bone healing?
- Whether type H vessel will be a biomarker for diagnosing bone healing in patients with open fracture?
- To find out a circulating indicator for type H vessel in patients with open fracture undergoing induced membrane technique.
Participants will be enrolled to collect tissues of induced membrane and blood samples to detect type H vessel and measure the biomarkers of type H vessel, investigating their correlation with the capacity of bone healing. To avoid selection bias of treatment, the grouping will be achieved by a randomized protocol qualified clinical trial center of Chang Gung Memorial Hospital to divide into with induced membrane and without induced membrane. Researchers will compare these two groups to test our hypothesis that type H vessel in important in induced membrane and their corresponding biomarkers.
Read the detailed description
The masquelet technique, also called an induced membrane technique (IMT), was first introduced to treat critical size bone defect up to 25 cm in 1986 by Pr. Alain Charles Masquelet et al. IMT is a two-stage surgical operation that recently provides a more popular option for the treatment of critical size bone defect as well as fracture nonunion. Basically, the first stage of IMT comprises the implantation of a polymethylmethacrylate (PMMA) cement spacer loaded with antibiotics into defect site. During 6 to 8 weeks, this spacer induces the formation and maturation of a thin layer called induced membrane surrounding it via a foreign body immune response. In stage II, the spacer is carefully removed while keeping induced membrane at the fracture site, autologous bone graft is then performed to provoke bone healing. IMT endows several beneficial effects including the relatively simple management versus vascularized fibular grafts and no significant difference in healing time among various defect sizes. Of note, multiple surgeries and long recovery time are the difficulties still needed to be conquered in patients treated with IMT. In view of the fact that induced membrane has been considered as an indispensable component for successful union, a more detailed and comprehensive analysis of it will improve the process of IMT to ameliorate those difficulties.
The clinical study design will follow the description in Chang Gung Medical Foundation Institutional Review Board, which will be begun in the first year until reaching 15 patients for each group. Briefly, patients of open fracture will be randomly divided into two groups to reduce selection bios, comprising spacer (with induced membrane) and without spacer groups (without induced membrane). In a without spacer group (No operation of stage I), soft tissues near fracture sites with a size of 1 cm2 will be collected to be used as an appropriate control of induced membrane (1 cm2) from the spacer group (Stage I + II) at the time point of stage II of IMT. Tissues will be dissected into three parts for proteomics, metabolomics, and paraffinized section, stored at minus 80 degrees prior to experiments. The section is imperative in this project to characterize type H vessel formation and the capacity of bone healing. For this purpose, immunohistochemistry (IHC) or Immunofluorescence (IF) will be performed to measure identified proteins from proteomics results in both of soft tissues and induced membrane. The characterized markers comprising cluster of differentiation 31 (CD31) and Endomucin (Emcn) will be used to detect type H vessels. Colorimetric methods including Masson's trichrome, Alcian blue, Alizarin red S, H\&E and Safranin O-Fast green can also be performed to unveil histological insights of induced membrane. In the multi-omics, tissues will be used to unveil novel targets, which will then be compared to the levels of vascular endothelial growth factor (VEGF) and osteocalcin. Furthermore, western blotting and real-time reverse transcriptase-Polymerase Chain Reaction (RT-PCR) will be performed to validate downstream regulation of the identified metabolites.
The venous blood (3ml in vacutainers with heparin) will be collected from both groups at the Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. The protocol was based on a report identifying VEGF as a potential biomarker of the union in IMT. After drawing, blood will be centrifuged (1000RPM, 10min at room temperature) for 30 minutes and stored at minus 80 degrees until analysis. Blood samples from the time point of collecting induced membrane are prepared for multi-omics analysis to identify systemic markers for type H vessel or induced membrane, and VEGF and osteocalcin will be used as serum indicators for bone mass. Blood samples from all time points will be used to identify a novel biomarker for type H vessels and bone healing. As for metabolite targets, targeted methods of metabolomics will be employed to verify them in blood. The time points for collecting blood samples of stage I will be the day of surgery, the next day of surgery, and 1, 2, and 4 weeks after surgery. As for stage II, the time points will be the day of surgery, the next day of surgery, and 1, 2, 12, and 14 weeks after surgery.
- Conditions
- Bone Injury
- Being tested
- induced membrane technique, Bone graft (Stage II of IMT)
- Keywords
- Induced membrane, Bone healing, Type H vessel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
induced membrane techniqueProcedure or surgery
Also called Masquelet technique
Masquelet technique, also called an induced membrane technique (IMT), was first introduced to treat critical size bone defect up to 25 cm in 1986 by Pr. Alain Charles Masquelet et al. IMT is a two-stage surgical operation that recently provides a more popular option for the treatment of critical size bone defect as well as fracture nonunion. Basically, first stage of IMT comprises the implantation of a polymethylmethacrylate (PMMA) cement spacer loaded with antibiotics into defect site. During 6 to 8 weeks, this spacer induces the formation and maturation of a thin layer called induced membrane surrounding it via a foreign body immune response. In stage II, the spacer is carefully removed while keeping induced membrane at the fracture site, autologous bone graft is then performed to provoke bone healing.
Bone graft (Stage II of IMT)Procedure or surgery
Bone graft is only performed in this group to provoke bone healing, as same as demonstrated in the stage II of IMT.
| Study group | Role | What they receive |
|---|---|---|
| with induced membrane | Experimental | operation of stage I and II Receives: Procedure: induced membrane technique |
| without induced membrane | Experimental | only stage II Receives: Procedure: Bone graft (Stage II of IMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The participants with open fracture will be assessed by the level of type H vessel
In each group, induced membrane and soft tissue collected at 8th weeks will be used to detect CD31 and Emcn by performing immunohistochemistry (IHC) or immunofluorescence (IF), two markers for identifying type H vessel that correlated to the capacity of bone healing. The staining will be quantified as units of intensity in values defined by software or area in pixels to assess the level of type H vessel in each participant.detecting the expression level in induced membrane and soft tissue at 8 weeks, and markers of bone healing as well as metabolites in blood of each point.
Measured: Induced membrane will be collected at 8th weeks of IMT performing procedures of stage II.
The participants with open fracture will be assessed by X-ray
The defect sites in these patients will be assessed the capacity of bone healing in a time-dependent manner, by quantifying the sizes of the defects from these images and representing them as the length in centimeter (cm) or area in cm2. These results will be aggregated with the level of type H vessel to report the correlation between bone healing and type H vessel.
Measured: Bone healing tracking will be up to 24 weeks after stage II operation.
The participants with open fracture will be assessed the metabolic alteration
Finding out a potential marker to predict the correlation mentioned above, bloods collected from patients in a time-dependent manner and tissue at 8th week will be assessed the metabolic alteration by performing analysis of Liquid chromatography-mass spectrometry (LC-MS/MS). The identified metabolites will be represented as a unit of concentration in micro molar. The levels of metabolites will also be aggregated with results of type H vessel and bone healing to report whether these identified metabolites will be a type H marker defining or predicting the capacity of bone healing.
Measured: Induced membrane will be collected at 8th weeks of IMT performing procedures of stage II. Blood will be a time-dependent manner through out this study up to 32 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2023
- Study start1 Apr 2023 (estimated)
- Primary completion1 Apr 2023 (estimated)
- Study completion2 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bone InjuryStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- HSU YUNG-HENG, MD, PhD, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05792371
- Sponsor's protocol ID
- 202201532B0A3
- Status last verified
- Jan 2023
- First submitted
- 15 Feb 2023
- Last updated
- 31 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Niikura T, Oda T, Jimbo N, Komatsu M, Oe K, Fukui T, Matsumoto T, Hayashi S, Matsushita T, Itoh T, Kuroda R. Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique. J Orthop Surg Res. 2022 Jan 15;17(1):29. doi: 10.1186/s13018-022-02922-y.
PubMed 35033126Tanner MC, Boxriker S, Haubruck P, Child C, Westhauser F, Fischer C, Schmidmaier G, Moghaddam A. Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique-A Pilot Study. J Clin Med. 2021 Feb 15;10(4):776. doi: 10.3390/jcm10040776.
PubMed 33672081
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Endothelial Cell-mediated Type H Vessel Formation in Induced Membrane-enhanced Bone Union of Patients With Critical Size Bone Defect
- ClinicalTrials.gov ID
- NCT05792371
- Acronym / sponsor ID
- 202201532B0A3
- Conditions
- Bone Injury
- Keywords
- Induced membrane, Bone healing, Type H vessel
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 Apr 2023 (estimated)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 2 Jan 2026 (estimated)
- First posted
- 31 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to test the role of type H vessel and investigate the mechanism of its regulation in induced membrane created by induced membrane technique in patients with open fracture, aged between 20 and 80.
The main questions to answer are:
- Whether type H vessel will be critical for induced membrane-mediated bone healing?
- Whether type H vessel will be a biomarker for diagnosing bone healing in patients with open fracture?
- To find out a circulating indicator for type H vessel in patients with open fracture undergoing induced membrane technique.
Participants will be enrolled to collect tissues of induced membrane and blood samples to detect type H vessel and measure the biomarkers of type H vessel, investigating their correlation with the capacity of bone healing. To avoid selection bias of treatment, the grouping will be achieved by a randomized protocol qualified clinical trial center of Chang Gung Memorial Hospital to divide into with induced membrane and without induced membrane. Researchers will compare these two groups to test our hypothesis that type H vessel in important in induced membrane and their corresponding biomarkers.
Detailed description
The masquelet technique, also called an induced membrane technique (IMT), was first introduced to treat critical size bone defect up to 25 cm in 1986 by Pr. Alain Charles Masquelet et al. IMT is a two-stage surgical operation that recently provides a more popular option for the treatment of critical size bone defect as well as fracture nonunion. Basically, the first stage of IMT comprises the implantation of a polymethylmethacrylate (PMMA) cement spacer loaded with antibiotics into defect site. During 6 to 8 weeks, this spacer induces the formation and maturation of a thin layer called induced membrane surrounding it via a foreign body immune response. In stage II, the spacer is carefully removed while keeping induced membrane at the fracture site, autologous bone graft is then performed to provoke bone healing. IMT endows several beneficial effects including the relatively simple management versus vascularized fibular grafts and no significant difference in healing time among various defect sizes. Of note, multiple surgeries and long recovery time are the difficulties still needed to be conquered in patients treated with IMT. In view of the fact that induced membrane has been considered as an indispensable component for successful union, a more detailed and comprehensive analysis of it will improve the process of IMT to ameliorate those difficulties.
The clinical study design will follow the description in Chang Gung Medical Foundation Institutional Review Board, which will be begun in the first year until reaching 15 patients for each group. Briefly, patients of open fracture will be randomly divided into two groups to reduce selection bios, comprising spacer (with induced membrane) and without spacer groups (without induced membrane). In a without spacer group (No operation of stage I), soft tissues near fracture sites with a size of 1 cm2 will be collected to be used as an appropriate control of induced membrane (1 cm2) from the spacer group (Stage I + II) at the time point of stage II of IMT. Tissues will be dissected into three parts for proteomics, metabolomics, and paraffinized section, stored at minus 80 degrees prior to experiments. The section is imperative in this project to characterize type H vessel formation and the capacity of bone healing. For this purpose, immunohistochemistry (IHC) or Immunofluorescence (IF) will be performed to measure identified proteins from proteomics results in both of soft tissues and induced membrane. The characterized markers comprising cluster of differentiation 31 (CD31) and Endomucin (Emcn) will be used to detect type H vessels. Colorimetric methods including Masson's trichrome, Alcian blue, Alizarin red S, H\&E and Safranin O-Fast green can also be performed to unveil histological insights of induced membrane. In the multi-omics, tissues will be used to unveil novel targets, which will then be compared to the levels of vascular endothelial growth factor (VEGF) and osteocalcin. Furthermore, western blotting and real-time reverse transcriptase-Polymerase Chain Reaction (RT-PCR) will be performed to validate downstream regulation of the identified metabolites.
The venous blood (3ml in vacutainers with heparin) will be collected from both groups at the Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. The protocol was based on a report identifying VEGF as a potential biomarker of the union in IMT. After drawing, blood will be centrifuged (1000RPM, 10min at room temperature) for 30 minutes and stored at minus 80 degrees until analysis. Blood samples from the time point of collecting induced membrane are prepared for multi-omics analysis to identify systemic markers for type H vessel or induced membrane, and VEGF and osteocalcin will be used as serum indicators for bone mass. Blood samples from all time points will be used to identify a novel biomarker for type H vessels and bone healing. As for metabolite targets, targeted methods of metabolomics will be employed to verify them in blood. The time points for collecting blood samples of stage I will be the day of surgery, the next day of surgery, and 1, 2, and 4 weeks after surgery. As for stage II, the time points will be the day of surgery, the next day of surgery, and 1, 2, 12, and 14 weeks after surgery.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| with induced membrane | Experimental | Procedure: induced membrane techniqueoperation of stage I and II |
| without induced membrane | Experimental | Procedure: Bone graft (Stage II of IMT)only stage II |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Accept the informed consent form
- Age: 20 years to 80 years
- Type II and III open fracture with 2-6.5 cm defect size
Key exclusion criteria (4 listed)
- Not accept the informed consent form
- Age smaller than 20 years and over 80 years
- Quit during the trial
- patients with Notifiable infectious diseases such as AIDS and hepatitis as well as cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| induced membrane techniqueAlso: Masquelet techniqueMasquelet technique, also called an induced membrane technique (IMT), was first introduced to treat critical size bone defect up to 25 cm in 1986 by Pr. Alain Charles Masquelet et al. IMT is a two-stage surgical operation that recently provides a more popular option for the treatment of critical size bone defect as well as fracture nonunion. Basically, first stage of IMT comprises the implantation of a polymethylmethacrylate (PMMA) cement spacer loaded with antibiotics into defect site. During 6 to 8 weeks, this spacer induces the formation and maturation of a thin layer called induced membrane surrounding it via a foreign body immune response. In stage II, the spacer is carefully removed while keeping induced membrane at the fracture site, autologous bone graft is then performed to provoke bone healing. | Procedure or surgery | with induced membrane |
| Bone graft (Stage II of IMT)Bone graft is only performed in this group to provoke bone healing, as same as demonstrated in the stage II of IMT. | Procedure or surgery | without induced membrane |
Primary outcome
The participants with open fracture will be assessed by the level of type H vessel
Time frame: Induced membrane will be collected at 8th weeks of IMT performing procedures of stage II.
In each group, induced membrane and soft tissue collected at 8th weeks will be used to detect CD31 and Emcn by performing immunohistochemistry (IHC) or immunofluorescence (IF), two markers for identifying type H vessel that correlated to the capacity of bone healing. The staining will be quantified as units of intensity in values defined by software or area in pixels to assess the level of type H vessel in each participant.detecting the expression level in induced membrane and soft tissue at 8 weeks, and markers of bone healing as well as metabolites in blood of each point.
The participants with open fracture will be assessed by X-ray
Time frame: Bone healing tracking will be up to 24 weeks after stage II operation.
The defect sites in these patients will be assessed the capacity of bone healing in a time-dependent manner, by quantifying the sizes of the defects from these images and representing them as the length in centimeter (cm) or area in cm2. These results will be aggregated with the level of type H vessel to report the correlation between bone healing and type H vessel.
The participants with open fracture will be assessed the metabolic alteration
Time frame: Induced membrane will be collected at 8th weeks of IMT performing procedures of stage II. Blood will be a time-dependent manner through out this study up to 32 weeks.
Finding out a potential marker to predict the correlation mentioned above, bloods collected from patients in a time-dependent manner and tissue at 8th week will be assessed the metabolic alteration by performing analysis of Liquid chromatography-mass spectrometry (LC-MS/MS). The identified metabolites will be represented as a unit of concentration in micro molar. The levels of metabolites will also be aggregated with results of type H vessel and bone healing to report whether these identified metabolites will be a type H marker defining or predicting the capacity of bone healing.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Results publication: PubMed 35033126Niikura T, Oda T, Jimbo N, Komatsu M, Oe K, Fukui T, Matsumoto T, Hayashi S, Matsushita T, Itoh T, Kuroda R. Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique. J Orthop Surg Res. 2022 Jan 15;17(1):29. doi: 10.1186/s13018-022-02922-y.
- Results publication: PubMed 33672081Tanner MC, Boxriker S, Haubruck P, Child C, Westhauser F, Fischer C, Schmidmaier G, Moghaddam A. Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique-A Pilot Study. J Clin Med. 2021 Feb 15;10(4):776. doi: 10.3390/jcm10040776.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
HSU YUNG-HENG, MD, PhD principal investigator
Chang Gung Memorial Hospital
Questions about this trial
What is this clinical trial studying?
A study testing induced membrane technique and Bone graft (Stage II of IMT) in people with Bone Injury, run by Chang Gung Memorial Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact HSU YUNG-HENG, MD, PhD ((03)3281200 ext. 2423, hsuyh@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The participants with open fracture will be assessed by the level of type H vessel (time frame: Induced membrane will be collected at 8th weeks of IMT performing procedures of stage II.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05792371, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2023; AzTrials last refreshed its copy on 8 Nov 2026.