Type 1 diabetes mellitus Nutritional, Metabolic, Endocrine Type 1 diabetes mellitus
Conditions
Interventions
Participants are randomised on a 2:1 basis to receive either Ustekinumab as intervention or saline as placebo. Participants will be given Ustekinumab subcutaneously (SC) in an enhanced dose depending
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 10/12/2019: 1. Clinical diagnosis of immune-mediated Type 1 diabetes mellitus as defined by American Diabetes Association 2. Commenced on insulin within 1 month of clinical diagnosis (defined as confirmed raised blood sugar (ADA criteria), not symptoms alone). 3. An interval of =100 days between the confirmed diagnosis (defined as first insulin dose) and the first dose of the IMP 4. Written and witnessed informed consent/assent to participate 5. Male or female, aged 12-18 years inclusive at the time of randomisation 6. Evidence of residual functioning beta-cells (serum C-peptide level > 0.2nmol/L in the MMTT test) 7. Positive for at least one islet autoantibody (GAD, IA-2, ZnT8) 8. Body weight 0.2nmol/L in the MMTT test) 7. Positive for at least one islet autoantibody (GAD, IA-2, ZnT8) 8. Body weight < 100 kg 9. Willing to record all insulin doses and blood glucose levels required for monitoring during the study, including reporting any hypoglycaemic events 10. Willing to consent to remote follow up via health records and telephone contact 11. Female participants have a negative urine test for pregnancy; all sexually active participants must agree to use adequate contraception (hormonal based contraception, double barrier contraception, abstinence) until 4 months following the date of their final treatment of IMP
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 10/12/2019: 1. Breastfeeding, pregnancy or unwillingness to comply with contraceptive advice and regular pregnancy testing throughout the trial 2. Prior exposure to Ustekinumab within 3 months of the first dose of IMP 3. Use of more than 10 mg prednisolone daily (or equivalent) for >5 days within 3 months of the first dose of IMP. Note: intranasal, inhaled and topical corticosteroid medications are permitted at recommended doses. Use of systemic corticosteroids during the trial should be avoided unless such treatment is medically necessary and alternative treatments are not considered safe or effective 4. Prior exposure to any anti-lymphocyte monoclonal antibody, such as anti-CD20, anti-thymocyte globulin (ATG), Rituximab (Rituxan®), or Alemtuzumab (Campath®) 5. Use of immunosuppressive or immunomodulatory therapies, including systemic steroids (e.g., methotrexate, cyclosporine, or anti-TNF agents) within 30 days prior to receiving the first dose and/or intent on using any monoclonal antibody therapy given for any indication for the duration (including follow up) of the trial 6. Use of any hypoglycaemia agents other than insulin, for more than 6 weeks, at any time prior to trial entry, including SGLT2 inhibitors. 7. Use of inhaled insulin 8. Known alcohol abuse, drug abuse 9. Evidence of active Hepatitis B, Hepatitis C, HIV or considered by the investigator to be at high risk for HIV infection 10. Significant systemic infection during the 6 weeks before the first dose of the IMP (e.g. infection requiring hospitalisation, major surgery, requiring IV antibiotic treatment). Other infections e.g. glandular fever, bronchitis, sinusitis, cellulitis, or urinary tract infections must be assessed on a case by case basis by the investigator to assess whether they are serious enough to warrant exclusion or delay to inclusion 11. History of current or past active tuberculosis (TB) infection and no latent tuberculosis according to the British Thoracic Society recommendations [27]. Active TB will be assessed using a mandatory chest x-ray and one of the following: a) a blood test e.g. T-spot (preferred), interferon gamma release assay (IGRA), quantiferon test b) the Mantoux skin test. A positive result from any TB test will exclude the subject from the study and the subject and their medical care team will be informed. An intermediate result from blood sample testing will not exclude the participant from randomisation if the chest x-ray is negative. The blood test for TB only needs to be repeated if there is a change in the perceived clinical risk of TB 12. Participants should not have had live immunisations (flu and others) for 1 month prior to trial entry and should not receive any during their time in the trial. Note that most injected (as opposed to nasal) influenza vaccines are not live vaccines and are permitted 13. Previous use of any other investigational drug within the 3 months prior to the first dose and/or intent on using any investigational drug for the duration (including follow up) of the trial 14. Recent (within 3 months) participant’s involvement in other research studies which, in the opinion of investigators, may adversely affect the safety of the participants or the results of the study 15. Significantly abnormal laboratory results during the screening period, other than those due to T1D 16. Prior allergic reaction, including anaphylaxis, to any component of the IMP product 17. Prior allergic re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mixed Meal Tolerance Test (MMTT) stimulated 2-hour insulin C-peptide area under the curve (AUC) at week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Number of responders (defined as participant who has HbA1c = 48mmol/mol and mean daily insulin use <0.5 IU/kg/day) measured over 7 consecutive days during the 2 weeks preceding the visit in treatment and placebo group measured at -2, 0, 4, 12, 20, 28, 36, 44 and 52 2. Mixed Meal tolerance Test C-peptide area under the curve values measured at week 28 3. HbA1c measured at weeks 0, 12, 28 and 52 4. Exogenous insulin requirement as reflected in mean daily insulin usage over 7 consecutive days (IU units/kg body weight/day) as recorded in capillary blood glucose testing meters or diaries prior to study visits at weeks 12, 28 and 52 5. Insulin dose adjusted HbA1c (IDAAC) measured at week 52 6. Glycaemic variability parameters downloaded from glucose monitoring at Weeks 0, 4, 12, 20, 28, 36, 44 and 52 7. Clinical hypoglycaemic events determined by patient diary reports and AE reports at week 52 8. Frequency and severity of all adverse events at week 52 9. Quality of life: fear of having a hypoglycaemic event measured using HYPOFEAR; diabetes treatment satisfaction measured using DTSQ; and paediatric quality of life measured using PedsQL. These will be administered to the participant and their parent/carer (parent versions available for each) and compared across time. The data from participants and their parents are also compared at each timepoint (weeks -2, 28 and 52) | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactKym Carter
Outcome results
None listed