Comparison of Day and Night Closed-loop With Faster-acting Insulin Aspart With Insulin Aspart

NCT ID: NCT03579615

Last Updated: 2022-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-23
• Study Completion Date: 2022-08-01

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

FIASP + closed loop device

Subjects randomised to FIASP and closed loop device will be invited to have blood samples taken at baseline, CGM training, competency assessment, and optimisation of treatment. This is followed by inpatient stay where patients will be using FIASP + closed loop intervention for 24 hours. 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).

Group Type: EXPERIMENTAL

FIASP + closed loop device

Intervention Type: 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).

Insulin aspart (standard of care insulin) + closed loop device

Subjects randomised to insulin aspart (standard of care insulin) and closed loop device will be invited to have blood samples taken at baseline, CGM training, competency assessment, and optimisation of treatment. This is followed by inpatient stay where patients will be using insulin aspart (standard of care insulin) + closed loop intervention for 24 hours.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).

Group Type: ACTIVE_COMPARATOR

Insulin aspart (standard of care insulin) + closed loop device

Intervention Type: DEVICE

Participants will be advised to maintain their usual insulin 24 hours prior to admission.

Interventions

FIASP + 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).

Intervention Type: DEVICE

Insulin aspart (standard of care insulin) + closed loop device

Participants will be advised to maintain their usual insulin 24 hours prior to admission.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Manchester University Hospitals NHS Foundation Trust

Manchester, , United Kingdom

Countries

United Kingdom

References

Thabit H, Mubita W, Rubio J, Karuppan M, Schofield J, Willinska ME, Hovorka R, Leelarathna L. Comparison of faster-acting aspart with insulin aspart under conditions mimicking underestimation or missed meal boluses in type 1 diabetes using closed-loop insulin delivery. Diabetes Obes Metab. 2023 Apr;25(4):1121-1124. doi: 10.1111/dom.14942. Epub 2022 Dec 27. No abstract available.

Reference Type: DERIVED

PMID: 36514847 (View on PubMed)

Other Identifiers

R04695

Identifier Type: -

Identifier Source: org_study_id