Diabetes Mellitus, Type 1
Conditions
Brief summary
The main objective of the study is to determine whether automated closed-loop using faster-acting insulin aspart will improve glucose control and reduce the burden of hypoglycaemia over a 23-hour period compared to insulin aspart under conditions mimicking under-estimation of meal carbohydrate content or missed meal bolus. Faster-acting insulin aspart (FIASP) is a novel formulation of insulin aspart in which two additional excipients (L-arginine and Niacinamide) have been added, resulting in accelerated initial absorption and more than double the glucose lowering effect in the first 30 minutes after subcutaneous administration using insulin pump. To date, no closed-loop study has been performed to evaluate the benefit of faster-acting aspart over insulin aspart during closed-loop system use.
Detailed description
This is an open-label, single-centre, two-period, randomised, cross over study. The study involves a screening visit to assess participant eligibility and two 24 hour in-patient stays at the clinical research facility during which day and night glucose levels will be controlled by the closed-loop system with either faster-acting insulin aspart or insulin aspart. Up to 22 adults with type 1 diabetes and treated with continuous subcutaneous insulin infusion will be recruited, aiming for 16 completed participants. Recruitment will take place at Manchester Diabetes Centre, Manchester Royal Infirmary, Manchester, UK. Participants will attend the Manchester Clinical Research Facility (MCRF), Manchester, on two occasions. In random order, they will undergo two closed-loop study days using either faster-acting insulin aspart or insulin aspart. During the study days, the closed-loop control algorithm will automatically modulate d insulin infusion rate based on real-time subcutaneous glucose sensor measurements. Participants will receive standardised meals with half usual meal bolus for the evening meal and no meal bolus for lunch time meal during each study day.
Interventions
DEVICEFIASP + closed loop device
Participants will be advised to change their usual insulin to the corresponding study visit insulin formulation, 24 hours prior to admission. (For example; if the participant is on insulin aspart, this will be changed to faster-acting aspart 24-hour prior to the admission for closed loop with faster-acting aspart and vice versa).
DEVICEInsulin aspart (standard of care insulin) + closed loop device
Participants will be advised to maintain their usual insulin 24 hours prior to admission.
Sponsors
Novo Nordisk A/S
Manchester University NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Masking description
FIASP vs standard of care insulin
Intervention model description
An open-label, single-centre, randomised, two-period, cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject is 18 years and older 2. The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative 3. The subject will have been an insulin pump user for at least 3 months 4. The subject is treated with any of the rapid acting insulin analogues 5. The subject is willing to adhere to study procedures 6. HbA1c ≥ 7.0% (53 mmol/mol) and ≤ 10 % (86mmol/mol) based on analysis from local laboratory or equivalent within 3 months prior to enrolment 7. The subject is literate in English
Exclusion criteria
* 1\. Non-type 1 diabetes mellitus including those secondary to chronic disease 2. Any other physical or psychological disease likely to interfere with the normal conduct of the study 3. Untreated celiac disease or hypothyroidism 4. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, Metformin, SGLT2 inhibitors, non-selective beta-blockers and MAO inhibitors etc. 5\. Known or suspected allergy against insulin 6. Subjects with clinical significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator 7. Total daily insulin dose \> 2 U/kg/day 8. Total daily insulin dose \< 10 U/day 9. Pregnancy, planned pregnancy, or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time spent in the target glucose range | 23 hours | Time spent in the target glucose range between 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on sensor glucose levels between the hours of 19:00 on day 1 and 18:00 hours on day 2 of the inpatient stay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incremental area under the curve of sensor glucose level within 4 hours of each meal | 4 hours | Incremental area under the curve of sensor glucose level during the first 4 hours after each meal |
| Time spent below target glucose | 23 hours | Time spent below target glucose (\<3.9mmol/l) (\<70mg/dl) |
| Time spent above target glucose | 23 hours | Time spent above target glucose (10.0 mmol/l) (180 mg/dl) |
| Average, coefficient of variation and standard deviation glucose levels | 23 hours | Average, coefficient of variation and standard deviation glucose levels |
| The time with sensor glucose levels < 3.5 mmol/l (63 mg/dl) | 23 hours | The time with sensor glucose levels \< 3.5 mmol/l (63 mg/dl) |
| Time spent in the target glucose range within 4 hours of each meal | 4 hours | Time spent in the target glucose range between 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on sensor glucose levels during the first 4 hours following each meal |
| The time with sensor glucose levels <2.8 mmol/l (50 mg/dl) | 23 hours | The time with sensor glucose levels \<2.8 mmol/l (50 mg/dl) |
| The time with sensor glucose levels in the significant hyperglycaemia | 23 hours | The time with sensor glucose levels in the significant hyperglycaemia (glucose levels \> 16.7 mmol/l) (300mg/dl) |
| Total, basal and bolus insulin dose | 23 hours | Total, basal and bolus insulin dose |
| AUC of glucose below 3.0mmol/l (54mg/dl) | 23 hours | AUC of glucose below 3.0mmol/l (54mg/dl) |
| The time with sensor glucose levels <3.0 (54mg/dl) | 23 hours | The time with sensor glucose levels \<3.0 (54mg/dl) |
Countries
United Kingdom
Outcome results
None listed