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Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump (BIG LEAP)

Primary Purpose

Type1 Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Aspart

About this trial

This is an interventional treatment trial for Type1 Diabetes Mellitus focused on measuring Continuous Glucose Monitoring, CGM, Continuous Subcutaneous Insulin Infusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female patients > 18 years of age with type 1 diabetes using CSII with any pump for > 12 months.
Females must be using adequate contraception, defined as oral contraceptive pill, barrier method of contraception, or surgical method (tubal ligation or hysterectomy).
Good glycemic control (HbA1c < 8.0%).
Patients are experienced in carbohydrate counting, evidenced by pump downloads showing frequent meal boluses with realistic carbohydrate entries, few over-rides of the pump bolus calculator, few to no omitted boluses (at least 3 boluses per day), and post-meal glucose levels generally below 200 mg/dl indicating accurate carbohydrate assessment.
Patients are regular (>85% of time) users of the Dexcom G5 or G6 CGM.
Pump download confirms correct use of insulin pump features, including appropriate use of bolus calculator with minimal overrides, entering carbohydrate content of meals, at least 3 boluses taken per day, appropriate use of correction boluses, and infusion set changes every 2 to 3 days.
No serious comorbidities including: retinopathy requiring active intervention, eGFR < 30, CV event within the previous 6 months, active malignancy with ongoing treatment, any condition requiring chronic use of systemic glucocorticoids, or any other condition which in the opinion of the investigator would interfere with the subject's ability to comply with the study protocol or acutely affect insulin requirements.
Able to comply with study protocol.
Ability to provide written informed consent prior to any study-related procedures.
-

Exclusion Criteria:

Subjects with type 2 diabetes.
Subjects with HbA1c > 8.0%
Subjects not using CSII and CGM (ie, on MDI)
Subjects inexperienced in the use of CSII, or whose pump download shows poor utilization of bolus calculator features, ie fewer than 2 boluses per day, lack of correction boluses, frequent overrides of the recommended boluses, unrealistic carbohydrate entries (suggestive of under-bolusing), not changing infusion set at least every 3 days, or other evidence of poor insulin pump usage.
Subjects inexperienced in or not regular users (>85% of time) of Dexcom G5 or G6 CGM
Subjects who are using a Medtronic pump with low blood glucose suspend who are unwilling to use the Dexcom CGM or to disengage the low blood glucose suspend feature of the pump.
Use of any other CGM than Dexcom G5 or G6.
Serious concomitant illness.
Females unwilling to use adequate contraception, intending to become pregnant, or breastfeeding.
Known or suspected allergy to study products, their excipients or related products.
Previous participation in this trial. Note: subjects who screen fail because of A1c may rescreen once if, in the opinion of the investigator, the HbA1c was explainable (ie, recent steroid injection or illness, etc) and atypical for the subject.
Hypoglycemic unawareness.
Episode of severe hypoglycemia (requiring assistance for treatment) within the previous 90 days.
-

Sites / Locations

Mountain Diabetes and Endocrine Center

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

NovoLog®-only

Novolog® and Tresiba® Group

Arm Description

In the aspart-Only group, the subject will only take aspart through the their pump. This study population will have an established expertise in diabetes self-management with previous knowledge of insulin pump therapy and Dexcom Continuous Glucose Monitoring (CGM). Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses. Aspart is put into their pump and delivered to their body through a small tube placed under your skin. In this NovoLog®-only treatment group, the subject will take aspart with each meal while your pump also gives you a slow, continuous dose of aspart for basal insulin. This treatment group is very similar (or even identical) to the treatment the subject was receiving prior to starting the study.

This study population will have an expertise in diabetes self-management with their insulin pump and Dexcom CGM. In the Novolog® and Tresiba® group, the subject will still take aspart via their pump for meals and correction boluses, but they will reduce the slow trickle (basal insulin) programmed in their pump to almost zero. Instead of receiving their normal basal insulin via CSII, the subject will injected degludec once or twice daily from an insulin pen for your basal insulin.

Outcomes

Primary Outcome Measures

Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM

Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM during the final 14 days of each treatment period during steady state (with basal insulin delivery as either one daily injection of insulin degludec or as insulin aspart via CSII)

Secondary Outcome Measures

Standard Deviation (SD) of blood glucose by CGM for two week period

SD of interstitial fluid glucose by CGM for 2 week period during each basal insulin delivery method. (Note: because the Dexcom Platinum G5 CGM is currently only FDA approved for 7 days of use, two contiguous CGM periods using 2 sensors, each for 7 days, will be performed to capture 2 weeks of continuous CGM data.) Dexcom G6 is approved by FDA for 10 days of use so 2 sensors will be used during the CGM periods.

SD of blood glucose by CGM during the nocturnal period

SD of blood glucose by CGM during the nocturnal period (midnight to 6 am) during each basal insulin delivery method

Percent time in hypoglycemia by CGM

Percent time in hypoglycemia by CGM, captured at 2 levels of hypoglycemia: BG < 54 mg/dl (level 2) and BG 55-69 mg/dl (level 1), for each basal insulin treatment.

Percent time in normoglycemia

Percent time in normoglycemia (BG 70 to 140 mg/dl) by CGM during each basal treatment period.

Time to recovery from level 2 hypoglycemia

Time to recovery from level 2 hypoglycemia (BG >70 with resolution of symptoms) on each treatment. If a second event (BG < 70 mg/dl) occurs within 60 minutes of a previous hypoglycemic event, this will be considered part of the same hypoglycemic episode.

Patient satisfaction

Patient satisfaction by TRIM-D questionnaires with each basal insulin treatment.

Patient satisfaction

Patient satisfaction by TRIM-DD questionnaires with each basal insulin treatment.

HbA1c

HbA1c after 20 weeks of each basal insulin treatment.

Total daily insulin dosage

Total daily insulin dose, total basal insulin dose, and total bolus insulin dose on each treatment.

Full Information

NCT ID

NCT04409587

First Posted

July 30, 2018

Last Updated

February 23, 2021

Sponsor

Mountain Diabetes and Endocrine Center

Collaborators

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT04409587

Brief Title

Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump

Acronym

BIG LEAP

Official Title

Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump: A Comparison of Insulin Degludec to Continuous Subcutaneous Infusion of Insulin Aspart for Basal Insulin Delivery in Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

April 12, 2018 (Actual)

Primary Completion Date

May 16, 2020 (Actual)

Study Completion Date

November 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mountain Diabetes and Endocrine Center

Collaborators

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this investigator-initiated trial is to compare the effect of a daily injection of insulin degludec vs. basal insulin delivery via Continuous Subcutaneous Insulin Infusion (CSII), both in combination with bolus insulin delivery via the patient's usual insulin pump with insulin aspart, on glycemic variability, overall blood glucose control and incidence of hypoglycemia, all assessed by continuous glucose monitor (CGM), as well as patient satisfaction, in patients with type 1 diabetes currently using CSII.

Detailed Description

The primary objective of this trial is to determine whether insulin degludec will provide an equally stable and consistent basal glycemic profile with lower glycemic variability as determined by Continuous Glucose Monitoring compared to insulin aspart delivered by Continuous Subcutaneous Insulin Infusion in patients with type 1 diabetes experienced in use of insulin pump therapy. Specifically, this study will determine if the percent time in the target glycemic range (70 to 180 mg/dl) by Continuous Glucose Monitoring is superior using insulin degludec than continuously infused insulin aspart, and if degludec is associated with lower glucose variability as assessed by the standard deviation (SD) of the mean daily glucose by Continuous Glucose Monitoring. Particular attention will be given to the nocturnal glucose profile (from midnight to 6 am) which most closely reflects basal insulin action as it is typically the time of day least affected by bolus insulin, food intake or exercise. Quality of life questionnaires regarding treatment preference will be used to capture patient preference for method of basal insulin delivery. RESEARCH DESIGN AND METHODS Study hypothesis: It is anticipated, based on the low glycemic variability of insulin degludec shown in glucose clamp studies and seen in clinical practice, that insulin degludec will provide more stable 24 hour basal insulin action than insulin aspart by Continuous Subcutaneous Insulin Infusion (CSII) in patients with type 1 diabetes. Primary endpoint: Percent time in euglycemia (BG 70 to 180 mg/dl) by Continuous Glucose Monitoring (CGM) during the final 14 days of each treatment period during steady state (with basal insulin delivery as either one daily injection of insulin degludec or as insulin aspart via CSII). Study type: This will be a randomized, cross-over, open label, single-center study consisting of a 20 week period on each of two basal insulin delivery methods, both in combination with insulin aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week insulin optimization period for titration of basal and bolus insulin doses, followed by a 16 week maintenance period. The final 2 weeks of the maintenance period during each treatment arm will be used for endpoint data collection. The treatment sequence will occur in random order. The study population will include patients with type 1 diabetes with good baseline glycemic control who are experienced in the use of both CSII and CGM; the cross-over design allows each subject to serve as his or her own control.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type1 Diabetes Mellitus

Keywords

Continuous Glucose Monitoring, CGM, Continuous Subcutaneous Insulin Infusion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Model Description

This will be a randomized, cross-over, open label, single-center study consisting of a 20 week period on each of two basal insulin delivery methods, both in combination with insulin aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week insulin optimization period for titration of basal and bolus insulin doses, followed by a 16 week maintenance period. The final 2 weeks of the maintenance period during each treatment arm will be used for endpoint data collection. The treatment sequence will occur in random order. The study population will include patients with type 1 diabetes with good baseline glycemic control who are experienced in the use of both Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitor; the cross-over design allows each subject to serve as his or her own control.

Masking

None (Open Label)

Masking Description

This is an unblinded study as the two basal insulin delivery methods (degludec via injection vs. aspart via CSII) cannot be blinded. One group of patients will first use degludec for 20 weeks then switch to CSII for 20 weeks. As all eligible patients who sign the IRB consent form are identified, a random number will be generated to determine the treatment with which they begin first. The other group of patients will start with CSII and after 20 weeks switch to Tresiba for 20 weeks. Randomization sequence will be determined by computerized randomization program. All patients will receive both treatments unless they drop out. Dropouts are unlikely since the participants are all regular continuing patients of the site's clinical practice.

Allocation

Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NovoLog®-only

Arm Type

No Intervention

Arm Description

Arm Title

Novolog® and Tresiba® Group

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Aspart

Other Intervention Name(s)

Degludec

Intervention Description

A population of well controlled patients with type 1 diabetes who are experienced in the use of both Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitor (CGM) was chosen in order to assess the effect of the change in glycemic profile using two different methods of basal insulin delivery. Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses. Replacing basal insulin delivery by CSII with a single daily injection of degludec will add minimal, if any, treatment burden which will be offset by potential therapeutic benefits. These benefits include the potential for reduced glycemic variability and the elimination of the risk of hyperglycemia and DKA with basal insulin interruption which can occur with infusion set occlusion or disgorging inherent to Continuous Subcutaneous Insulin Infusion.

Primary Outcome Measure Information:

Title

Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM

Description

Time Frame

46 weeks

Secondary Outcome Measure Information:

Title

Standard Deviation (SD) of blood glucose by CGM for two week period

Description

Time Frame

46 weeks

Title

SD of blood glucose by CGM during the nocturnal period

Description

SD of blood glucose by CGM during the nocturnal period (midnight to 6 am) during each basal insulin delivery method

Time Frame

46 weeks

Title

Percent time in hypoglycemia by CGM

Description

Percent time in hypoglycemia by CGM, captured at 2 levels of hypoglycemia: BG < 54 mg/dl (level 2) and BG 55-69 mg/dl (level 1), for each basal insulin treatment.

Time Frame

46 weeks

Title

Percent time in normoglycemia

Description

Percent time in normoglycemia (BG 70 to 140 mg/dl) by CGM during each basal treatment period.

Time Frame

46 weeks

Title

Time to recovery from level 2 hypoglycemia

Description

Time Frame

46 weeks

Title

Patient satisfaction

Description

Patient satisfaction by TRIM-D questionnaires with each basal insulin treatment.

Time Frame

46 weeks

Title

Patient satisfaction

Description

Patient satisfaction by TRIM-DD questionnaires with each basal insulin treatment.

Time Frame

46 weeks

Title

HbA1c

Description

HbA1c after 20 weeks of each basal insulin treatment.

Time Frame

46 weeks

Title

Total daily insulin dosage

Description

Total daily insulin dose, total basal insulin dose, and total bolus insulin dose on each treatment.

Time Frame

46 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female patients > 18 years of age with type 1 diabetes using CSII with any pump for > 12 months. Females must be using adequate contraception, defined as oral contraceptive pill, barrier method of contraception, or surgical method (tubal ligation or hysterectomy). Good glycemic control (HbA1c < 8.0%). Patients are experienced in carbohydrate counting, evidenced by pump downloads showing frequent meal boluses with realistic carbohydrate entries, few over-rides of the pump bolus calculator, few to no omitted boluses (at least 3 boluses per day), and post-meal glucose levels generally below 200 mg/dl indicating accurate carbohydrate assessment. Patients are regular (>85% of time) users of the Dexcom G5 or G6 CGM. Pump download confirms correct use of insulin pump features, including appropriate use of bolus calculator with minimal overrides, entering carbohydrate content of meals, at least 3 boluses taken per day, appropriate use of correction boluses, and infusion set changes every 2 to 3 days. No serious comorbidities including: retinopathy requiring active intervention, eGFR < 30, CV event within the previous 6 months, active malignancy with ongoing treatment, any condition requiring chronic use of systemic glucocorticoids, or any other condition which in the opinion of the investigator would interfere with the subject's ability to comply with the study protocol or acutely affect insulin requirements. Able to comply with study protocol. Ability to provide written informed consent prior to any study-related procedures. - Exclusion Criteria: Subjects with type 2 diabetes. Subjects with HbA1c > 8.0% Subjects not using CSII and CGM (ie, on MDI) Subjects inexperienced in the use of CSII, or whose pump download shows poor utilization of bolus calculator features, ie fewer than 2 boluses per day, lack of correction boluses, frequent overrides of the recommended boluses, unrealistic carbohydrate entries (suggestive of under-bolusing), not changing infusion set at least every 3 days, or other evidence of poor insulin pump usage. Subjects inexperienced in or not regular users (>85% of time) of Dexcom G5 or G6 CGM Subjects who are using a Medtronic pump with low blood glucose suspend who are unwilling to use the Dexcom CGM or to disengage the low blood glucose suspend feature of the pump. Use of any other CGM than Dexcom G5 or G6. Serious concomitant illness. Females unwilling to use adequate contraception, intending to become pregnant, or breastfeeding. Known or suspected allergy to study products, their excipients or related products. Previous participation in this trial. Note: subjects who screen fail because of A1c may rescreen once if, in the opinion of the investigator, the HbA1c was explainable (ie, recent steroid injection or illness, etc) and atypical for the subject. Hypoglycemic unawareness. Episode of severe hypoglycemia (requiring assistance for treatment) within the previous 90 days. -

Facility Information:

Facility Name

Mountain Diabetes and Endocrine Center

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28803

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data and statistical analysis will be available to any researcher with appropriate request

IPD Sharing Time Frame

post study, up to 5 years

IPD Sharing Access Criteria

email principal investigator

Citations:

PubMed Identifier

20091571

Citation

Misso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD005103. doi: 10.1002/14651858.CD005103.pub2.

Results Reference

result

PubMed Identifier

25998289

Citation

Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, Maahs DM, Tamborlane WV; T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015 Jun;38(6):971-8. doi: 10.2337/dc15-0078.

Results Reference

result

PubMed Identifier

22594461

Citation

Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012 Sep;14(9):859-64. doi: 10.1111/j.1463-1326.2012.01627.x. Epub 2012 Jun 7.

Results Reference

result

PubMed Identifier

28672316

Citation

Lane W, Bailey TS, Gerety G, Gumprecht J, Philis-Tsimikas A, Hansen CT, Nielsen TSS, Warren M; Group Information; SWITCH 1. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):33-44. doi: 10.1001/jama.2017.7115.

Results Reference

result

PubMed Identifier

27629148

Citation

Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.

Results Reference

result

Citation

Novo Nordisk. (2015). TRESIBA® (insulin degludec injection) Label. 28-29

Results Reference

result

Citation

Novo Nordisk. (2000). NovoLog (insulin aspart [rDNA origin]) injection label. 21-22

Results Reference

result

Links:

URL

http://online.liebertpub.com/doi/full/10.1089/DIA.2017.0175

Description

Hauzenber JR et al. Diab Technol Therapeutics 2017

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Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump

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