Group 1: Trauma Operation for Otherwise Healthy PatientsRING UB LIGASENCT02256241
The Role of RING Ubiquitin Ligases in Biologic and Oncologic Processes in Tissues of Mesenchymal Origin
An observational study of Group 1: Trauma Operation for Otherwise Healthy Patients and Group 2: Primary Tumors of Mesenchymal Origin, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
Stage 1: Bone marrow will be collected from otherwise healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. The bone marrow will be collected from disposable tissue that is removed during the normal sequence of the surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Group 1: Trauma Operation for Otherwise Healthy Patients, Group 2: Primary Tumors of Mesenchymal Origin
- How many people
- 90 participants
- Where
- 1 siteIsrael
- Study dates
- Oct 2014to Jul 2019
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 1. Healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. 2. Patients with malignancies of musculoskeletal origin.
Who may be able to join
- Healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients.
- patients with malignancies of musculoskeletal origin.
Who cannot join
- Any malignancy in the past or active infection.
- Group 2:
- Any malignancy of unknown origin or malignancy of multiple origins or active infection.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Rambam MC
Haifa
Rostislav Novak, MD/PhD, +972502061188, n_rosti@rambam.health.gov.il
Amir M Orian, MD/PhD, +97248295448/9, mdoryan@tx.technion.ac.il
About this study
Stage 1:
Bone marrow will be collected from otherwise healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. The bone marrow will be collected from disposable tissue that is removed during the normal sequence of the surgery. These cells will be used for:
Read more
Establishment of the role of RING ubiquitin ligases in osteogenic progenitors proliferation and differentiation in culture.
- To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells: To test the correlation between levels of RING ubiquitin ligases and degree of osteogenic differentiation, we will extract mesenchymal precursor cells from the collected tissue and test the mRNA protein level of RING ubiquitin ligases upon induction of differentiation. Specifically, we will compare the levels of RING ubiquitin ligases before and after the initiation of differentiational stimulus in time dependent manner by western blot and real time PCR analysis.
II. To test the impact of specific RING ubiquitin ligases on differentiation of human mesenchymal precursor cells: to test the impact of RING ubiquitin ligases on the differentiation of mesenchymal precursor cell from the collected tissue by testing the expression of classical differentiational bone markers by flow cytometry (fibronectin, CD105) and by Alkaline phosphatase (ALP) activity assay. For this aim we developed both a constitutive and Dox-regulated conditional overexpression and shRNA lenti-viral systems that enables efficient modulation of these RING ubiquitin ligases level.
III. Determine the role of RING ubiquitin ligases in proliferation and survival of human mesenchymal precursor cells: Via inhibition or overexpression of ligases in mesenchymal progenitor cells we will test the role of these ligases in proliferation and survival of mesenchymal precursors by using MTT assay, Propidion-Iodid (PI) and tunnel assays in flow cytometry analysis.
Stage 2:
Collection of connective tissue from patients with malignancies of musculoskeletal origin. The tissue that will be used is part of the resected tumor specimens. The tissue will be used for:
The establishment of the role/s of RING ligases in musculoskeletal cancers using cell culture and in vivo activation. Test if the expression of selected positive candidates from stage 1 correlates with cancer development and progression in human-derived samples Independently of our mechanistic experiment we aim to determine the relevance of these ligases to human musculoskeletal cancers. As the first step we will screen primary tumor biopsies at the protein level correlates with cancer grade and prognosis. Toward this aim we recently generated a highly specific several anti-monoclonal antibodies in our laboratory as well use comercial available antibodies .
Read the detailed description
Stage 1:
Bone marrow will be collected from otherwise healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. The bone marrow will be collected from disposable tissue that is removed during the normal sequence of the surgery. These cells will be used for:
Establishment of the role of RING ubiquitin ligases in osteogenic progenitors proliferation and differentiation in culture.
- To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells: To test the correlation between levels of RING ubiquitin ligases and degree of osteogenic differentiation, we will extract mesenchymal precursor cells from the collected tissue and test the mRNA protein level of RING ubiquitin ligases upon induction of differentiation. Specifically, we will compare the levels of RING ubiquitin ligases RING ubiquitin ligases before and after the initiation of differentiational stimulus in time dependent manner by western blot and real time PCR analysis.
II. To test the impact of RING ubiquitin ligases on differentiation of human mesenchymal precursor cells: to test the impact of RING ubiquitin ligases on the differentiation of mesenchymal precursor cell from the collected tissue by testing the expression of classical differentiational bone markers by flow cytometry (fibronectin, CD105) and by Alkaline phosphatase (ALP) activity assay. For this aim we developed both a constitutive and Dox-regulated conditional RING ubiquitin ligases overexpression and shRNA lenti-viral systems that enables efficient modulation of RING ubiquitin ligases level.
III. Determine the role of RING ubiquitin ligases in proliferation and survival of human mesenchymal precursor cells: We will test the role of their in proliferation and survival of mesenchymal precursors by using MTT assay, Propidion-Iodid (PI) and tunnel assays in flow cytometry analysis.
Stage 2:
Collection of connective tissue from patients with malignancies of musculoskeletal origin. The tissue that will be used is part of the resected tumor specimens. The tissue will be used for:
The establishment of the role/s of RING ubiquitin ligases in musculoskeletal cancers using cell culture and in vivo.
- Test the role of our in proliferation and survival in musculoskeletal cancers: Using our lentiviral systems we will test the biological impact of inhibition and overexpression in musculoskeletal neoplastic cells.
II. Test whether inhibition or overexpression of these ligases impacts the biology of musculoskeletal cancers.We will check if inhibition of these ligases in malignant cells of musculoskeletal origin by lenti-viral infections induces differentiation. Infected cells will be analyzed for expression of differentiational markers in flow cytometry and immunohistochemistry.
III. Test if expression of RING ubiquitin ligases correlates with cancer development and progression in human-derived samples Independently of our mechanistic experiment we aim to determine the relevance of RING ubiquitin ligases to human musculoskeletal cancers.
Patients consent will be signed after properly informed at time of pre-surgical preparation visit. In cases when pre-surgical visit is not held consent will be signed prior to the day of surgery.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| The role of RING ubiquitin ligases in osteogenic progenitors | Bone marrow (BM) will be collected from healthy patients undergoing orthopedic surgery. BM will be collected from disposable tissue that is removed during the normal sequence of the surgery. | |
| The role of RING ubiquitin ligases in musculoskeletal cancer | Collection of connective tissue from patients with tumors of musculoskeletal origin - a part of the resected tumor specimens. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protein and mRNA levels of RING ubiquitin ligases during osteogenesis
To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells. We will extract mesenchymal precursor cells from the collected tissue and test the mRNA and protein levels of RING ubiquitin ligases upon induction of differentiation.
Measured: 5 years
Protein and mRNA levels of RING ubiquitin ligases in musculoskeletal tumors and its correlation to staging and grading
It is not clear if RING ubiquitin ligases protein levels are elevated in soft tissue-derived cancers (primary and metastatic tumors) and whether there is a correlation between RING ubiquitin ligases levels and staging and grading of soft tissue-derived cancers. For this reason, we will check whether RING ubiquitin ligases expression correlates with cancer development and progression in human-derived samples. We will determine the relevance of RING ubiquitin ligases to human musculoskeletal cancers. To do this we will screen primary tumor biopsies for RNA and protein levels of RING ubiquitin ligases .
Measured: Time Frame: * 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionJul 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Group 1: Trauma Operation for Otherwise Healthy PatientsStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Technion, Israel Institute of Technology
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02256241
- Sponsor's protocol ID
- 0180-14-RMB
- Acronym
- RING UB LIGASE
- Status last verified
- Feb 2015
- First submitted
- 29 Jul 2014
- Last updated
- 24 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of RING Ubiquitin Ligases in Biologic and Oncologic Processes in Tissues of Mesenchymal Origin
- ClinicalTrials.gov ID
- NCT02256241
- Acronym / sponsor ID
- RING UB LIGASE / 0180-14-RMB
- Conditions
- Group 1: Trauma Operation for Otherwise Healthy Patients, Group 2: Primary Tumors of Mesenchymal Origin
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- Technion, Israel Institute of Technology
- Study start
- Oct 2014
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 3 Oct 2014 (estimated)
- 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.
Stage 1:
Bone marrow will be collected from otherwise healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. The bone marrow will be collected from disposable tissue that is removed during the normal sequence of the surgery. These cells will be used for:
Establishment of the role of RING ubiquitin ligases in osteogenic progenitors proliferation and differentiation in culture.
- To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells: To test the correlation between levels of RING ubiquitin ligases and degree of osteogenic differentiation, we will extract mesenchymal precursor cells from the collected tissue and test the mRNA protein level of RING ubiquitin ligases upon induction of differentiation. Specifically, we will compare the levels of RING ubiquitin ligases before and after the initiation of differentiational stimulus in time dependent manner by western blot and real time PCR analysis.
II. To test the impact of specific RING ubiquitin ligases on differentiation of human mesenchymal precursor cells: to test the impact of RING ubiquitin ligases on the differentiation of mesenchymal precursor cell from the collected tissue by testing the expression of classical differentiational bone markers by flow cytometry (fibronectin, CD105) and by Alkaline phosphatase (ALP) activity assay. For this aim we developed both a constitutive and Dox-regulated conditional overexpression and shRNA lenti-viral systems that enables efficient modulation of these RING ubiquitin ligases level.
III. Determine the role of RING ubiquitin ligases in proliferation and survival of human mesenchymal precursor cells: Via inhibition or overexpression of ligases in mesenchymal progenitor cells we will test the role of these ligases in proliferation and survival of mesenchymal precursors by using MTT assay, Propidion-Iodid (PI) and tunnel assays in flow cytometry analysis.
Stage 2:
Collection of connective tissue from patients with malignancies of musculoskeletal origin. The tissue that will be used is part of the resected tumor specimens. The tissue will be used for:
The establishment of the role/s of RING ligases in musculoskeletal cancers using cell culture and in vivo activation. Test if the expression of selected positive candidates from stage 1 correlates with cancer development and progression in human-derived samples Independently of our mechanistic experiment we aim to determine the relevance of these ligases to human musculoskeletal cancers. As the first step we will screen primary tumor biopsies at the protein level correlates with cancer grade and prognosis. Toward this aim we recently generated a highly specific several anti-monoclonal antibodies in our laboratory as well use comercial available antibodies .
Detailed description
Stage 1:
Bone marrow will be collected from otherwise healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. The bone marrow will be collected from disposable tissue that is removed during the normal sequence of the surgery. These cells will be used for:
Establishment of the role of RING ubiquitin ligases in osteogenic progenitors proliferation and differentiation in culture.
- To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells: To test the correlation between levels of RING ubiquitin ligases and degree of osteogenic differentiation, we will extract mesenchymal precursor cells from the collected tissue and test the mRNA protein level of RING ubiquitin ligases upon induction of differentiation. Specifically, we will compare the levels of RING ubiquitin ligases RING ubiquitin ligases before and after the initiation of differentiational stimulus in time dependent manner by western blot and real time PCR analysis.
II. To test the impact of RING ubiquitin ligases on differentiation of human mesenchymal precursor cells: to test the impact of RING ubiquitin ligases on the differentiation of mesenchymal precursor cell from the collected tissue by testing the expression of classical differentiational bone markers by flow cytometry (fibronectin, CD105) and by Alkaline phosphatase (ALP) activity assay. For this aim we developed both a constitutive and Dox-regulated conditional RING ubiquitin ligases overexpression and shRNA lenti-viral systems that enables efficient modulation of RING ubiquitin ligases level.
III. Determine the role of RING ubiquitin ligases in proliferation and survival of human mesenchymal precursor cells: We will test the role of their in proliferation and survival of mesenchymal precursors by using MTT assay, Propidion-Iodid (PI) and tunnel assays in flow cytometry analysis.
Stage 2:
Collection of connective tissue from patients with malignancies of musculoskeletal origin. The tissue that will be used is part of the resected tumor specimens. The tissue will be used for:
The establishment of the role/s of RING ubiquitin ligases in musculoskeletal cancers using cell culture and in vivo.
- Test the role of our in proliferation and survival in musculoskeletal cancers: Using our lentiviral systems we will test the biological impact of inhibition and overexpression in musculoskeletal neoplastic cells.
II. Test whether inhibition or overexpression of these ligases impacts the biology of musculoskeletal cancers.We will check if inhibition of these ligases in malignant cells of musculoskeletal origin by lenti-viral infections induces differentiation. Infected cells will be analyzed for expression of differentiational markers in flow cytometry and immunohistochemistry.
III. Test if expression of RING ubiquitin ligases correlates with cancer development and progression in human-derived samples Independently of our mechanistic experiment we aim to determine the relevance of RING ubiquitin ligases to human musculoskeletal cancers.
Patients consent will be signed after properly informed at time of pre-surgical preparation visit. In cases when pre-surgical visit is not held consent will be signed prior to the day of surgery.
Study design
- Observational model
- Cohort
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| The role of RING ubiquitin ligases in osteogenic progenitors | – | –Bone marrow (BM) will be collected from healthy patients undergoing orthopedic surgery. BM will be collected from disposable tissue that is removed during the normal sequence of the surgery. |
| The role of RING ubiquitin ligases in musculoskeletal cancer | – | –Collection of connective tissue from patients with tumors of musculoskeletal origin - a part of the resected tumor specimens. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 1. Healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients. 2. Patients with malignancies of musculoskeletal origin.
Key inclusion criteria (2 listed)
- Healthy patients undergoing orthopedic surgery - arthroplasty for the treatment of degenerative joint disease or traumatised patients.
- patients with malignancies of musculoskeletal origin.
Key exclusion criteria (3 listed)
- Any malignancy in the past or active infection.
- Any malignancy of unknown origin or malignancy of multiple origins or active infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Protein and mRNA levels of RING ubiquitin ligases during osteogenesis
Time frame: 5 years
To determine the levels of RING ubiquitin ligases mRNA and protein in differentiating human mesenchymal precursor cells. We will extract mesenchymal precursor cells from the collected tissue and test the mRNA and protein levels of RING ubiquitin ligases upon induction of differentiation.
Protein and mRNA levels of RING ubiquitin ligases in musculoskeletal tumors and its correlation to staging and grading
Time frame: Time Frame: * 5 years
It is not clear if RING ubiquitin ligases protein levels are elevated in soft tissue-derived cancers (primary and metastatic tumors) and whether there is a correlation between RING ubiquitin ligases levels and staging and grading of soft tissue-derived cancers. For this reason, we will check whether RING ubiquitin ligases expression correlates with cancer development and progression in human-derived samples. We will determine the relevance of RING ubiquitin ligases to human musculoskeletal cancers. To do this we will screen primary tumor biopsies for RNA and protein levels of RING ubiquitin ligases .
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2015.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Group 1: Trauma Operation for Otherwise Healthy Patients and Group 2: Primary Tumors of Mesenchymal Origin, run by Rambam Health Care Campus at 1 site in Israel.
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 2 inclusion and 3 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 24 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Protein and mRNA levels of RING ubiquitin ligases during osteogenesis (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Feb 2015.