Type 1 DiabetesPhase 1/2DF-IL2NCT01353833
Dose-effect Relationship of Low-dose IL-2 in Type 1 Diabetes
A Phase 1/2 study testing Aldesleukin in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
IL-2 is an inducer of regulatory T cells (Treg), a population of lymphocytes that fail to control the autoimmune destruction of beta-cells in patients with Type 1 Diabetes (T1D). The investigators recently showed that low dose IL-2 is well tolerated in patients with an autoimmune disease. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Aldesleukin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- May 2011to Apr 2012
- Phase
- Phase 1/2
- 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 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age [18-50] years;
- With a T1D:
- Treated with insulin for ≤ 2 years,
- With at least one auto-antibody among: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 ;
- No clinically relevant abnormal value for hematology, biochemistry, liver and kidney function
- Lymphocyte [1000-4000]/ mm3
- Informed consent signed by the patient and the investigator before any intervention necessary for the trial.
Who cannot join
- Contra-indications to IL2 :
- Hypersensibility to IL-2 or its excipients,
- Severe cardiopathy
- Ongoing infection requiring antibiotherapy,
- O2 Saturation ≤ 90 %
- Severe impairment of a vital organ
Show all 13Show fewer
- Previous organ allograft
- Non authorized concomitant treatment : i.e. immuno-modulators, cytotoxic, drug modifying glycemia
- Cancer progressing or cured for less than 5 years except for primary basal cell carcinoma or carcinoma in situ of the uterine cervix.
- Participation to another clinical investigation in < 3 months
- Pregnant or lactating women
- Male or female in age of procreation without efficient contraception during the study
- No affiliation to National Health Insurance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose-effect Relationship of Repeated Administration of Low-dose IL-2 Versus Placebo on the Kinetic of Regulatory T Cells in Patients With Type 1 Diabetes
IL-2 is an inducer of regulatory T cells (Treg), a population of lymphocytes that fail to control the autoimmune destruction of beta-cells in patients with Type 1 Diabetes (T1D). The investigators recently showed that low dose IL-2 is well tolerated in patients with an autoimmune disease. The investigators aim to use IL-2 to induce/stimulate Treg in T1D patients. This study will investigate the dose effect relationship of low dose IL-2 for Treg induction such as to optimize the risk benefit ratio for this treatment in T1D. By Treg induction, the investigators aim to protect the remaining/regenerating β-cells from autoimmune destruction, thus improving or even curing T1D.
Read the detailed description
Rationale:
Type 1 diabetes (T1D) results from an autoimmune destruction of beta-pancreatic cells that regulatory T cells (Treg) fail to control. This is in part due to a deficit in production of, or response to, interleukin 2 (IL-2). This cytokine is essential to Treg development, survival and function. Importantly, while IL-2 also contributes to the activation of effector T cells (Teff), IL-2/IL-2 receptor signal transduction threshold is much lower for Treg than Teff. Thus low-dose IL-2 could be a specific Treg inducer/stimulator.
The investigators then recently showed that low-dose IL-2 could cure recent onset diabetes in NOD mice that develop spontaneous diabetes considered as the best model of human T1D. A 5-day treatment with IL-2 could cure over 30% of the mice versus 0% for controls.
With these premises, the investigators propose to explore if Treg induction could be obtained in patients who may have a deficit in production of, or response to, IL-2. Defining the dose effect relationship of low dose IL-2 for Treg induction will optimize the risk benefit ratio for IL-2 in T1D.
Principal objective:
To define the dose-effect relationship of low dose IL-2 for Treg induction in patient with recent onset diabetes
Evaluation Criteria:
- Efficacy Kinetic variation of Treg proportions within CD4+ T cells in peripheral blood from Day+0 to Day+60.
- Tolerance Evaluation by clinical exams, laboratory tests and monitoring of side effects. The criterion for terminating the study will be the occurrence of one serious unexpected side effect in the month following IL-2 first administration in at least 2 patients.
Study plan:
After inclusion (Day0), the patient receives a 5-day course of IL-2 or placebo. Patients are randomized in 4 arms receiving either a placebo, or IL-2 doses of 0,33 - 1 or 3 millions UI/day. Laboratory follow-up of peripheral blood T cell subsets will be performed at D0 to D6 (daily), D15, D22 and D60 by immunophenotyping and transcriptomics.
Tolerance will be evaluated at D0-6, D15, D22 and D60.
Methodology:
Double blind placebo controlled randomized study, with 4 parallel groups. Patients will have T1D of autoimmune origin attested by the presence of auto-antibodies (at least one of: anti-islet, anti-GAD, anti-IA2 or anti-ZnT8), with a diagnostic inferior or equal to 24 months.
Study length:
Study length = 9 months Patient participation = 2 months Inclusion period = 6 months
- Conditions
- Type 1 Diabetes
- Being tested
- Aldesleukin
- 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.
AldesleukinDrug
Also called IL2
0.33 ; 1 ; 3 ; 0 millions IU of IL-2 per day for arm 1 to 4, respectively. 1 s.c. injection per day for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| IL2-4 | Placebo comparator | Not described Receives: Drug: Aldesleukin |
| IL2-2 | Experimental | 1 millions IU of IL-2 per day Receives: Drug: Aldesleukin |
| IL2-3 | Experimental | 3 millions IU of IL-2 per day Receives: Drug: Aldesleukin |
| IL2-1 | Experimental | 0.33 millions IU of IL-2 per day Receives: Drug: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kinetic parameters of Treg proportions variation within CD4+ T cells in peripheral blood
Measured: from Day+0 to Day+60
Secondary outcomes (1)
Improvement of residual secretion of insulin assessed by the AUC of peptide C during a standardized test meal in IL-2 vs placebo treated patients
Measured: at Day+0 and Day+60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2011 (estimated)
- Study startMay 2011
- Primary completionOct 2011
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Davis Klatzmann, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353833
- Sponsor's protocol ID
- P101101
- Other IDs
- 2010-024499-24
- Acronym
- DF-IL2
- Status last verified
- May 2011
- First submitted
- 12 May 2011
- Last updated
- 23 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, Fonfrede M, Rosenzwajg M, Bernard C, Klatzmann D. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):295-305. doi: 10.1016/S2213-8587(13)70113-X. Epub 2013 Oct 8.
PubMed 24622415
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-effect Relationship of Repeated Administration of Low-dose IL-2 Versus Placebo on the Kinetic of Regulatory T Cells in Patients With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01353833
- Acronym / sponsor ID
- DF-IL2 / P101101
- Conditions
- Type 1 Diabetes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 16 May 2011 (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.
IL-2 is an inducer of regulatory T cells (Treg), a population of lymphocytes that fail to control the autoimmune destruction of beta-cells in patients with Type 1 Diabetes (T1D). The investigators recently showed that low dose IL-2 is well tolerated in patients with an autoimmune disease. The investigators aim to use IL-2 to induce/stimulate Treg in T1D patients. This study will investigate the dose effect relationship of low dose IL-2 for Treg induction such as to optimize the risk benefit ratio for this treatment in T1D. By Treg induction, the investigators aim to protect the remaining/regenerating β-cells from autoimmune destruction, thus improving or even curing T1D.
Detailed description
Rationale:
Type 1 diabetes (T1D) results from an autoimmune destruction of beta-pancreatic cells that regulatory T cells (Treg) fail to control. This is in part due to a deficit in production of, or response to, interleukin 2 (IL-2). This cytokine is essential to Treg development, survival and function. Importantly, while IL-2 also contributes to the activation of effector T cells (Teff), IL-2/IL-2 receptor signal transduction threshold is much lower for Treg than Teff. Thus low-dose IL-2 could be a specific Treg inducer/stimulator.
The investigators then recently showed that low-dose IL-2 could cure recent onset diabetes in NOD mice that develop spontaneous diabetes considered as the best model of human T1D. A 5-day treatment with IL-2 could cure over 30% of the mice versus 0% for controls.
With these premises, the investigators propose to explore if Treg induction could be obtained in patients who may have a deficit in production of, or response to, IL-2. Defining the dose effect relationship of low dose IL-2 for Treg induction will optimize the risk benefit ratio for IL-2 in T1D.
Principal objective:
To define the dose-effect relationship of low dose IL-2 for Treg induction in patient with recent onset diabetes
Evaluation Criteria:
- Efficacy Kinetic variation of Treg proportions within CD4+ T cells in peripheral blood from Day+0 to Day+60.
- Tolerance Evaluation by clinical exams, laboratory tests and monitoring of side effects. The criterion for terminating the study will be the occurrence of one serious unexpected side effect in the month following IL-2 first administration in at least 2 patients.
Study plan:
After inclusion (Day0), the patient receives a 5-day course of IL-2 or placebo. Patients are randomized in 4 arms receiving either a placebo, or IL-2 doses of 0,33 - 1 or 3 millions UI/day. Laboratory follow-up of peripheral blood T cell subsets will be performed at D0 to D6 (daily), D15, D22 and D60 by immunophenotyping and transcriptomics.
Tolerance will be evaluated at D0-6, D15, D22 and D60.
Methodology:
Double blind placebo controlled randomized study, with 4 parallel groups. Patients will have T1D of autoimmune origin attested by the presence of auto-antibodies (at least one of: anti-islet, anti-GAD, anti-IA2 or anti-ZnT8), with a diagnostic inferior or equal to 24 months.
Study length:
Study length = 9 months Patient participation = 2 months Inclusion period = 6 months
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IL2-4 | Placebo comparator | Drug: Aldesleukin |
| IL2-2 | Experimental | Drug: Aldesleukin1 millions IU of IL-2 per day |
| IL2-3 | Experimental | Drug: Aldesleukin3 millions IU of IL-2 per day |
| IL2-1 | Experimental | Drug: Aldesleukin0.33 millions IU of IL-2 per day |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age [18-50] years;
- With a T1D:
- Treated with insulin for ≤ 2 years,
- With at least one auto-antibody among: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 ;
- No clinically relevant abnormal value for hematology, biochemistry, liver and kidney function
Key exclusion criteria (13 listed)
- Contra-indications to IL2 :
- Hypersensibility to IL-2 or its excipients,
- Severe cardiopathy
- Ongoing infection requiring antibiotherapy,
- O2 Saturation ≤ 90 %
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 |
|---|---|---|
| AldesleukinAlso: IL20.33 ; 1 ; 3 ; 0 millions IU of IL-2 per day for arm 1 to 4, respectively. 1 s.c. injection per day for 5 days. | Drug | IL2-1, IL2-2, IL2-3, IL2-4 |
Primary outcome
Kinetic parameters of Treg proportions variation within CD4+ T cells in peripheral blood
Time frame: from Day+0 to Day+60
1 secondary outcome
Improvement of residual secretion of insulin assessed by the AUC of peptide C during a standardized test meal in IL-2 vs placebo treated patients
Time frame: at Day+0 and Day+60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2012.
- Derived from this study: PubMed 24622415Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, Fonfrede M, Rosenzwajg M, Bernard C, Klatzmann D. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):295-305. doi: 10.1016/S2213-8587(13)70113-X. Epub 2013 Oct 8.
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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.
Davis Klatzmann, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Aldesleukin in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 inclusion and 13 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: finished, as of the sponsor's last update on 23 Apr 2012. 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 France. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kinetic parameters of Treg proportions variation within CD4+ T cells in peripheral blood (time frame: from Day+0 to Day+60). 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 NCT01353833, which also lists 1 linked publication.
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 2012.