Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump

NCT04409587 | Completed Phase 4 FDA Drug

• 1 other identifier: MDEC2018
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1 Diabetes Mellitus

Keywords

Continuous Glucose Monitoring; CGM; Continuous Subcutaneous Insulin Infusion

Outcome Measures

Primary Outcomes (1)

• 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)

  46 weeks

Secondary Outcomes (9)

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

  46 weeks

• SD of blood glucose by CGM during the nocturnal period

  46 weeks

• Percent time in hypoglycemia by CGM

  46 weeks

• Percent time in normoglycemia

  46 weeks

• Time to recovery from level 2 hypoglycemia

  46 weeks

Study Arms (2)

NovoLog®-only

NO INTERVENTION

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.

Novolog® and Tresiba® Group

ACTIVE COMPARATOR

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.

Drug: Aspart

Interventions

Aspart DRUG

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.

Also known as: Degludec

Novolog® and Tresiba® Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mountain Diabetes and Endocrine Center: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Mountain Diabetes and Endocrine Center

Asheville, North Carolina, 28803, United States

Location

Related Publications (7)

• 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;2010(1):CD005103. doi: 10.1002/14651858.CD005103.pub2.

  PMID: 20091571 RESULT

• 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.

  PMID: 25998289 RESULT

• 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.

  PMID: 22594461 RESULT

• 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.

  PMID: 28672316 RESULT

• 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.

  PMID: 27629148 RESULT

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

  RESULT

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

  RESULT

Related Links

• Hauzenber JR et al. Diab Technol Therapeutics 2017

MeSH Terms

Interventions

Insulin Aspart; insulin degludec

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: June 1, 2020
• Study Start: April 12, 2018
• Primary Completion: May 16, 2020
• Study Completion: November 1, 2020
• Last Updated: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: post study, up to 5 years
• Access Criteria: email principal investigator

Locations

US (1)