Type I DiabetesNCT02117518
Selective Immunotargeting of Pathogenic CD8 T Cells of Type 1 Diabetes Patients
An observational study of Type I Diabetes, run by Migal Galilee Research Institute at 1 site in Israel.
Trial summary
It is well established that CD8 and CD4 T cells reactive against defined islet antigens are associated with initiation and progression of Type 1 Diabetes (T1D). In previous work, we have demonstrated that it is possible to redirect T cells against pathogenic T cells via chimeric peptide/MHC/CD3-zeta receptors in a… Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Type I Diabetes
- What is being tested?
- blood drawing
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- May 2014to May 2016
- 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 Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: T1D patients who were diagnosed up to 3 years prior to recruitment
Who may be able to join
- Children and young adults, ages between 0-25 who were diagnosed with T1D no more than 3 years prior to enrollment.
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
Israel1 site
Ziv Medical Center
Safed, 13100
Gideon Gross, PhD, +97246953554, gidi@migal.org.il
About this study
It is well established that CD8 and CD4 T cells reactive against defined islet antigens are associated with initiation and progression of Type 1 Diabetes (T1D). In previous work, we have demonstrated that it is possible to redirect T cells against pathogenic T cells via chimeric peptide/MHC/CD3-zeta receptors in a peptide-specific manner and to prevent, or inhibit diabetes in NOD mice. In this study we intend to extend this approach to T cells of T1D patients. Working hypothesis: Beta cell-reactive CD8 T cells of human T1D patients can be immuno-targeted by their own gene-modified cytotoxic T lymphocytes (CTLs). Aims: Our major aim is to demonstrate, in a set of ex-vivo experiments, such immunotargeting with T cells derived from T1D patients at the Ziv Medical Center. To this end we will stimulate and expand autoreactive CD8 cells in blood samples of T1D patients and target them, ex-vivo, with genetically-reprogrammed CTLs which are present in the same blood samples.
Read the detailed description
To obtain proof-of-principle of our approach we have initiated tight collaboration between the Laboratory of Immunology at MIGAL Galilee Research Institute, Kiryat Shmona (MIGAL) and Breinin Center for Type 1 Diabetes and Endocrinology at the Ziv Medical Center in Safed (Ziv). In this study we will first identify carriers of the HLA-A0201 allele among pediatric and young adult T1D patients at Ziv. We will then screen the T cell pool in the peripheral blood samples of these patients for CD8 T cells reactive against any of 3 known HLA-A0201-binding peptides associated with autoreactivity in T1D: Insulin beta chain 10-18, IGRP 265-73 and IGRP 222-230. The influenza virus-derived peptide MP 58-66 will serve as reference. Next we will isolate polyclonal CD8 T cells from blood samples of the same patients, activate and expand them ex-vivo and transfect them via electroporation with in-vitro-transcribed mRNA encoding the respective peptide/MHC/CD3-zeta construct(s). We will then perform co-culture experiments assessing the ability of the mRNA-transfected T cells to kill the autoreactive T cells of the same patient in a peptide-selective manner.
- Conditions
- Type I Diabetes
- Being tested
- blood drawing
- Keywords
- type 1 diabetes, autoreactive T cells, beta cell peptides, genetically modified T cells, mRNA electroporation
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood drawingOther
| Study group | Role | What they receive |
|---|---|---|
| no treatment | T1D patients at ages 0-25 Receives: Other: blood drawing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification, isolation, propagation and targeting of autoreactive T cells from T1D patients
The ability of the genetically-modified cells to target and kill target autologous autoreactive CD8 T cells will be analyzed by CFSE and HLA-I tetramer staining using flow cytometry and IFN gamma production using ELISPOT.
Measured: 2 years from the final approval of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionDec 2015 (estimated)
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type I DiabetesStudies 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
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Migal Galilee Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ziv Medical Center
- Responsible party
- Sponsor
- Investigators
- Gideon Gross, PhD, Study director, Migal Galilee Research InstituteOrna Gottfried, MD, Principal investigator, Ziv Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117518
- Sponsor's protocol ID
- 0063-13
- Status last verified
- Apr 2014
- First submitted
- 16 Apr 2014
- Last updated
- 23 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Immunotargeting of Pathogenic CD8 T Cells of Type 1 Diabetes Patients
- ClinicalTrials.gov ID
- NCT02117518
- Acronym / sponsor ID
- 0063-13
- Conditions
- Type I Diabetes
- Keywords
- type 1 diabetes, autoreactive T cells, beta cell peptides, genetically modified T cells, mRNA electroporation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Migal Galilee Research InstituteUniversity, hospital or other
- Collaborators
- Ziv Medical Center
- Study start
- May 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 21 Apr 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.
It is well established that CD8 and CD4 T cells reactive against defined islet antigens are associated with initiation and progression of Type 1 Diabetes (T1D). In previous work, we have demonstrated that it is possible to redirect T cells against pathogenic T cells via chimeric peptide/MHC/CD3-zeta receptors in a peptide-specific manner and to prevent, or inhibit diabetes in NOD mice. In this study we intend to extend this approach to T cells of T1D patients. Working hypothesis: Beta cell-reactive CD8 T cells of human T1D patients can be immuno-targeted by their own gene-modified cytotoxic T lymphocytes (CTLs). Aims: Our major aim is to demonstrate, in a set of ex-vivo experiments, such immunotargeting with T cells derived from T1D patients at the Ziv Medical Center. To this end we will stimulate and expand autoreactive CD8 cells in blood samples of T1D patients and target them, ex-vivo, with genetically-reprogrammed CTLs which are present in the same blood samples.
Detailed description
To obtain proof-of-principle of our approach we have initiated tight collaboration between the Laboratory of Immunology at MIGAL Galilee Research Institute, Kiryat Shmona (MIGAL) and Breinin Center for Type 1 Diabetes and Endocrinology at the Ziv Medical Center in Safed (Ziv). In this study we will first identify carriers of the HLA-A0201 allele among pediatric and young adult T1D patients at Ziv. We will then screen the T cell pool in the peripheral blood samples of these patients for CD8 T cells reactive against any of 3 known HLA-A0201-binding peptides associated with autoreactivity in T1D: Insulin beta chain 10-18, IGRP 265-73 and IGRP 222-230. The influenza virus-derived peptide MP 58-66 will serve as reference. Next we will isolate polyclonal CD8 T cells from blood samples of the same patients, activate and expand them ex-vivo and transfect them via electroporation with in-vitro-transcribed mRNA encoding the respective peptide/MHC/CD3-zeta construct(s). We will then perform co-culture experiments assessing the ability of the mRNA-transfected T cells to kill the autoreactive T cells of the same patient in a peptide-selective manner.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| no treatment | – | Other: blood drawingT1D patients at ages 0-25 |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- T1D patients who were diagnosed up to 3 years prior to recruitment
Key inclusion criteria (1 listed)
- Children and young adults, ages between 0-25 who were diagnosed with T1D no more than 3 years prior to enrollment.
Key exclusion criteria (1 listed)
- none
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 |
|---|---|---|
| blood drawing | Other | no treatment |
Primary outcome
Identification, isolation, propagation and targeting of autoreactive T cells from T1D patients
Time frame: 2 years from the final approval of study
The ability of the genetically-modified cells to target and kill target autologous autoreactive CD8 T cells will be analyzed by CFSE and HLA-I tetramer staining using flow cytometry and IFN gamma production using ELISPOT.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
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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.
Gideon Gross, PhD study director
Migal Galilee Research Institute
Orna Gottfried, MD principal investigator
Ziv Medical Center
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 Type I Diabetes, run by Migal Galilee Research Institute 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 1 inclusion and 1 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 23 Apr 2014. 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?
Identification, isolation, propagation and targeting of autoreactive T cells from T1D patients (time frame: 2 years from the final approval of study). 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 23 Apr 2014.