Pilot Clinical Trial of Ustekinumab in Patients With New-onset T1D (UST1D)
In type 1 diabetes (T1D), immune defense cells in the body attack and destroy insulin-producing beta cells leaving affected people with a lifelong need for daily insulin injections. Even with insulin injections, blood glucose (sugar) control is imperfect and leads to many health complications and a shortened life span. This is a pilot clinical trial to test the safety of a drug, ustekinumab, in 20 adult subjects with recent-onset T1D. Ustekinumab is currently licensed for use in psoriasis where it has proven to be both highly effective and safe and so the investigators hope to see a similar effect in T1D. This trial will also be used to determine the best dosage and frequency of the drug to be given to people with T1D to help design future studies on the drug's effectiveness. The investigators hope that if the drug can block immune cells soon after the development of diabetes, any remaining insulin-producing cells may be protected, and regenerate, thus producing more insulin so that individuals may be insulin free, or require less insulin.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Ustekinumab in Patients With New-onset Type 1 Diabetes|
- Primary Safety Endpoints (composite outcome measure) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Rate, frequency and severity of all adverse events including; hypoglycemic episodes; injection reactions; hypersensitivity reactions; evidence of infection and posterior leukoencephalopathy syndrome.
- Vital signs, standard hematology and chemistry tests, physical examinations.
- Immunological Endpoints (composite outcome measure) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Immune phenotyping via flow cytometry of all Interleukin (IL)-12, IL-23, IL-17, Interferon(IFN)-γ secreting immune subsets.
- Basic immune phenotyping of white blood cell subsets.
- Human leukocyte antigen(HLA)- A, B, C, DR, DP, DQ typing.
- Fluorospot (ELISpot) analysis for IL-17 and IFN-γ secretion in response to whole insulin and antigens for Cluster of differentiation (CD)8+ and CD4+ T cells .
- Luminex assessment of serum cytokines IL-17, IFN-γ, IL-12 and IL-23.
- Regulatory T cell : Effector T cell ratio
- CD154 based assays to determine diabetogenic antigen specific responses of T helper cells.
- Epigenetic assessment of Treg phenotype and function.
- Exploratory (composite outcome measure) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Mixed-meal tolerance test (MMTT) - stimulated 2-hour C-peptide area under the curve (AUC) at weeks 4, 28 and 52.
- Insulin use in units per kg body weight per day at weeks 4, 16, 28, 40 and 52.
- HbA1C levels at weeks 4, 16, 28, 40 and 52.
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Four cohorts of 5 subjects will be recruited:
Group 1: Five subjects will be given Ustekinumab 45mg SC at 0, 4, 16, 28 and 40 weeks.
Group 2: Five subjects will be given Ustekinumab 90mg SC at 0, 4, 16, 28 and 40 weeks.
Group 3: Five subjects will be given Ustekinumab 45 mg SC at 0,4 and 16 weeks.
Group 4: Five subjects will be given Ustekinumab 90mg SC at 0, 4 and 16 weeks.
Other Name: Stelara
The investigators will perform an open-label pilot safety study (Phase I/II clinical trial) with a total of 20 adult (18-35 years old) subjects with recent-onset T1D. There will be four study cohorts, which will be recruited sequentially all to the treatment arm: five subjects will be given ustekinumab, 45mg subcutaneously (SC) at 0, 4, 16, 28 and 40weeks, five subjects will be given ustekinumab, 90mg SC at weeks 0, 4, 16, 28 and 40, five subjects will be given 45mg SC at weeks 0, 4 and 16 and five subjects will be given 90mg subcutaneously (SC) at weeks 0, 4 and 16. Recruitment and screening for the pilot study will be completed within the first 6 months. The follow up period is 1 year from the first dose.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02117765
|Contact: Tom Elliott, MBBS, FRCPCfirstname.lastname@example.org|
|Contact: Marla Inducil, BSc Pharm, MD, CCRP||+1604 628 7253 ext email@example.com|
|Canada, British Columbia|
|Vancouver, British Columbia, Canada, V5Z 1M9|
|Contact: Marla Inducil, BSc Pharm, MD, CCRP +16048754634 firstname.lastname@example.org|
|Principal Investigator: Tom Elliott, MBBS, FRCPC|
|Principal Investigator:||Jan Dutz, MD FRCPC||Professor Department of Dermatology and Skin Science University of British Columbia|
|Study Director:||Ashish Marwaha, BMBCh PhD||University of British Columbia|