Clinical trial NCT03579615: Comparison of Day and Night Closed-loop With Faster-acting Insulin Aspart With Insulin Aspart
Official title: An Open-label, Single-centre, Randomised, Two-period, Cross-over Study to Assess the Efficacy and Safety of Day and Night Automated Closed-loop Glucose Control for 24 Hours in Adults With Type 1 Diabetes Comparing Faster-acting Insulin Aspart With Insulin Aspart
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
Collaborators: name: Novo Nordisk A/S
First posted: 2018-07-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: An open-label, single-centre, randomised, two-period, cross-over study
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time spent in the target glucose range
timeFrame: 23 hours
Secondary outcomes:
measure: Time spent in the target glucose range within 4 hours of each meal
timeFrame: 4 hours
measure: Incremental area under the curve of sensor glucose level within 4 hours of each meal
timeFrame: 4 hours
measure: Time spent below target glucose
timeFrame: 23 hours
measure: Time spent above target glucose
timeFrame: 23 hours
measure: Average, coefficient of variation and standard deviation glucose levels
timeFrame: 23 hours
measure: The time with sensor glucose levels < 3.5 mmol/l (63 mg/dl)
timeFrame: 23 hours
measure: The time with sensor glucose levels <3.0 (54mg/dl)
timeFrame: 23 hours
measure: The time with sensor glucose levels <2.8 mmol/l (50 mg/dl)
timeFrame: 23 hours
measure: The time with sensor glucose levels in the significant hyperglycaemia
timeFrame: 23 hours
measure: Total, basal and bolus insulin dose
timeFrame: 23 hours
measure: AUC of glucose below 3.0mmol/l (54mg/dl)
timeFrame: 23 hours
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Manchester University Hospitals NHS Foundation Trust
Study officials:
References: