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Type 1 DiabetesPhase 1/2DILfrequencyNCT02265809

Adaptive Study of IL-2 Dose Frequency on Regulatory T Cells in Type 1 Diabetes

A Phase 1/2 study testing Aldesleukin in people with Type 1 Diabetes, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Type 1 diabetes (T1D) is the most common severe autoimmune disease worldwide and is caused by the body's immune destruction of its own insulin producing pancreatic beta cells leading to insulin deficiency and development of elevated blood sugars. Read more about this study

Who is it for?
Ages 18 to 70 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?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteUnited Kingdom
Study dates
3 Oct 2014to 26 May 2016
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Type 1 diabetes
  • 18-70 years of age
  • Duration of diabetes less than 60 months from diagnosis
  • Written informed consent to participate

Who cannot join

  • Hypersensitivity to aldesleukin or any of the excipients
  • History of severe cardiac disease
  • History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that had been resected for cure or cervical carcinoma in situ)
  • History or concurrent use of immunosuppressive agents or steroids
  • History of unstable diabetes with recurrent hypoglycaemia
  • History of live vaccination two weeks prior to first treatment
Show all 15Show fewer
  • Active autoimmune hyper or hypothyroidism
  • Active clinical infection
  • Major pre-existing organ dysfunction or previous organ allograft
  • Females who are pregnant, lactating or intend to get pregnant during the study
  • Males who intend to father a pregnancy during the study
  • Donation of more than 500 ml of blood within 2 months prior to aldesleukin administration
  • Participation in a previous therapeutic clinical trial within 2 months prior to aldesleukin administration
  • Abnormal ECG
  • Abnormal full blood count, chronic renal failure (Stage 3,4,5) and/or evidence of severely impaired liver function (ALT/AST > 3xULN at screening; alkaline phosphatase and bilirubin 2xULN at screening (isolated bilirubin >2xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%))

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Wellcome Trust Clinical Research Facility, Addenbrookes Hospital

    Cambridge, Cambridgeshire, CB2 0QQ

Other trials in United Kingdom

About this study

Official title: Adaptive Study of IL-2 Dose Frequency on Regulatory T Cells in Type 1 Diabetes (DILfrequency)

Type 1 diabetes (T1D) is the most common severe autoimmune disease worldwide and is caused by the body's immune destruction of its own insulin producing pancreatic beta cells leading to insulin deficiency and development of elevated blood sugars. Currently, medical management of T1D focuses on intensive insulin replacement therapy to limit complications (retinopathy, nephropathy, neuropathy); nevertheless clinical outcomes remain suboptimal. There are intensive efforts to design novel immunotherapies that can arrest the autoimmune process and thereby preserve residual insulin production leading to fewer complications and better clinical outcomes.

Genetics are in part the cause of T1D and the majority of genes contributing to T1D produce proteins involved in immune regulation (called "tolerance"). A key player in immune tolerance is a molecule called interleukin-2 (IL-2) which enhances the ability of cells called T regulatory (Treg) cells to suppress the destruction the insulin producing beta cells. Aldesleukin is a human recombinant IL-2 product produced by recombinant DNA technology using a genetically engineered E. coli strain expressing an analogue of the human IL-2 gene. There is substantial data to suggest that ultra-low doses (ULD) of IL-2 (aldesleukin) can arrest the autoimmune mediated destruction of pancreatic beta cells by the induction of functional Treg cells.

The former study "Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes" (DILT1D) (NCT 01827735) was a single dose mechanistic study designed to establish the doses of IL-2 (aldesleukin) required to induce a minimal Treg increase (0.1 fold from baseline) or to induce a slightly larger Treg increase (0.2 fold from baseline) (maximal increase). Following on from the DILT1D study, the goal of the DILfrequency study is to use an adaptive design to determine the optimal dose and frequency of ULD IL-2 (aldesleukin) to maximize Treg function by frequently injecting ultra-low doses of IL-2 (aldesleukin). The responsiveness of each T1D participant to a particular frequency of IL-2 (aldesleukin) administration informs the frequency of dosing given to the next patient. This strategy focuses on improving the function of regulatory T cells that are exquisitely sensitive to IL-2 (aldesleukin).

Conditions
Type 1 Diabetes
Being tested
Aldesleukin
Keywords
Interleukin 2, Type 1 diabetes, T regulatory cells, Adaptive trial
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.

Study groups in NCT02265809
Study groupRoleWhat they receive
AldesleukinExperimentalAldesleukin will be administered subcutaneously at varying doses and frequencies for a period of up to 98 days from first administration depending on the treatment assignment. The maximum dose allowed is 0.6 X 10^6 IU/m2.
Receives: Drug: Aldesleukin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline of CD4 T regulatory cells, CD4 T effector cells and CD25 expression on T regulatory cells during treatment with ultra low dose IL-2

    Fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

Secondary outcomes (9)

  1. T regulatory cell number, phenotype and proliferation

    Measured by fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  2. T effector cell number, phenotype and proliferation

    Measured by fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  3. Natural Killer cell number, phenotype and proliferation

    Measured by fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  4. B lymphocyte cell number, phenotype and proliferation

    Measured by fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  5. T cell and Natural killer cell intracellular signalling

    Measured by fluorescence-activated cell sorting

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  6. Full blood count

    Measured by automatic analyser

    Measured: Visits 1-12 (between day -30 and day -1 up to a maximum of approximately day 98 depending on treatment assignment)

  7. Blood levels of IL-2, IL-6, IL-10, TNF-alpha, soluble CD25, IP-10, soluble rIL-6, and CRP

    Measured by enzyme-linked immunosorbent assay

    Measured: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)

  8. Change in metabolic control

    Blood glucose, HbA1c, C-peptide, insulin use and autoantibody status

    Measured: Visits 1-12 (between day -30 and day -1 up to a maximum of approximately day 98 depending on treatment assignment)

  9. Safety and tolerability

    Assessed by clinical history, physical examination, temperature, blood pressure, heart rate, 12-Lead electrocardiogram (ECGs), clinical laboratory tests, and adverse event recording

    Measured: Visits 1-12 (between day -30 and day -1 up to a maximum of approximately day 98 depending on treatment assignment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2014 (estimated)
  2. Study start3 Oct 2014
  3. Primary completion26 May 2016
  4. Study completion26 May 2016

Resources

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
Basic science
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02265809
Sponsor's protocol ID
DILfrequency
Acronym
DILfrequency
Status last verified
Aug 2018
First submitted
8 Oct 2014
Last updated
21 Aug 2018
Results posted
No
Data monitoring committee
No

Publications

  • Waldron-Lynch F, Kareclas P, Irons K, Walker NM, Mander A, Wicker LS, Todd JA, Bond S. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open. 2014 Jun 4;4(6):e005559. doi: 10.1136/bmjopen-2014-005559.

    PubMed 24898091

  • Truman LA, Pekalski ML, Kareclas P, Evangelou M, Walker NM, Howlett J, Mander AP, Kennet J, Wicker LS, Bond S, Todd JA, Waldron-Lynch F. Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study. BMJ Open. 2015 Dec 8;5(12):e009799. doi: 10.1136/bmjopen-2015-009799.

    PubMed 26646829

  • Zhang JY, Whalley JP, Knight JC, Wicker LS, Todd JA, Ferreira RC. SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile. Genome Med. 2023 Sep 12;15(1):69. doi: 10.1186/s13073-023-01227-x.

    PubMed 37700317

  • Seelig E, Howlett J, Porter L, Truman L, Heywood J, Kennet J, Arbon EL, Anselmiova K, Walker NM, Atkar R, Pekalski ML, Rytina E, Evans M, Wicker LS, Todd JA, Mander AP, Bond S, Waldron-Lynch F. The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes. JCI Insight. 2018 Oct 4;3(19):e99306. doi: 10.1172/jci.insight.99306.

    PubMed 30282826

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 Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

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 4 inclusion and 15 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 21 Aug 2018. 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 United Kingdom. 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.

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?

Change from baseline of CD4 T regulatory cells, CD4 T effector cells and CD25 expression on T regulatory cells during treatment with ultra low dose IL-2 (time frame: Visits 2-12 (day 0 up to a maximum of approximately day 98 depending on treatment assignment)). 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 NCT02265809, which also lists 4 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 21 Aug 2018.

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