Evaluation of Fiasp® (Fast Acting Insulin Aspart) in 670G Hybrid Closed-Loop Therapy

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03554486
• Collaborator: Medtronic (Industry)
• Enrollment: 27
• Locations: 2
• Arms: 2
• Actual Duration (Months): 8.2
• Patients Per Site: 13.5
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

This is a pilot outpatient study conducted at Stanford to obtain preliminary data on how Fiasp® works in a closed-loop system and to determine if any changes need to be made to the 670G pump to optimize the use of Fiasp®.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Fiasp; Drug: Novolog	Phase 4

Detailed Description

This will be a randomized cross-over blinded study and to see how the 670G pump responds to the introduction of Fiasp® insulin. Subjects enrolled in the study will have a 2 week period of optimization with weekly assessments of their Carelink download before entering the blinded phase of the study. They will use their usual home insulin during the optimization phase. They will then be started on their first blinded insulin (aspart or Fiasp®) which they will use for 2 weeks, before they cross-over to the other insulin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Subjects will be randomly assigned to start with either Fiasp insulin or Novolog insulin. After 2 weeks, they will start the previously unassigned insulin and continue using it for another 2 weeks.Subjects will be randomly assigned to start with either Fiasp insulin or Novolog insulin. After 2 weeks, they will start the previously unassigned insulin and continue using it for another 2 weeks.
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blinded
• Primary Purpose: Treatment
• Official Title: Evaluation of Fiasp® (Fast Acting Insulin Aspart) in 670G Hybrid Closed-Loop Therapy: To Assess How the 670G System Adapts to the Introduction of Fiasp® Insulin
• Actual Study Start Date: Jul 23, 2018
• Actual Primary Completion Date: Mar 30, 2019
• Actual Study Completion Date: Mar 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fiasp then Novolog Following a 2-week run-in period for pump-setting adjustments and monitoring, participants 1 will use Fiasp insulin for 2 weeks, followed by Novolog insulin for 2 weeks. Both the subject and the investigator will be blinded to which group the subject is assigned.	Drug: Fiasp; Fiasp insulin will be used for 2 weeks with the 670G hybrid closed-loop system; Other Names: Fast Acting Insulin Aspart ; Drug: Novolog; Novolog insulin will be used for 2 weeks with the 670G hybrid closed-loop system; Other Names: Insulin Aspart
Experimental: Novolog then Fiasp Following a 2-week run-in period for pump-setting adjustments and monitoring, participants 1 will use Novolog insulin for 2 weeks, followed by Fiasp insulin for 2 weeks. Both the subject and the investigator will be blinded to which group the subject is assigned.	Drug: Fiasp; Fiasp insulin will be used for 2 weeks with the 670G hybrid closed-loop system; Other Names: Fast Acting Insulin Aspart ; Drug: Novolog; Novolog insulin will be used for 2 weeks with the 670G hybrid closed-loop system; Other Names: Insulin Aspart

Outcome Measures

Primary Outcome Measures

1. Percentage of Time in Range: Sensor Glucose Values Between 70-180 mg/dl [7 days (during 2nd half of 2-week intervention period)]

   Measured as percentage of time in range (days).

2. Percentage of Time in Range: Sensor Glucose Readings <70 mg/dl [7 days (during 2nd half of 2-week intervention period)]

   Percentage of time in range (days) as a measure of hypoglycemia.

Secondary Outcome Measures

1. Mean Sensor Glucose in mg/dl [7 days (during 2nd half of 2-week intervention period)]

   Mean sensor data over the second week of using a randomized, blinded insulin.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Clinical diagnosis of type 1 diabetes and using 670G pump for at least 1 month, and willing to have the 670G pump downloaded into a Carelink Clinical research database.

2. The diagnosis of type 1 diabetes is based on the investigator's judgment; C-peptide level and antibody determinations are not needed.

3. Age ≥18 years

4. Using Novolog or Fiasp® insulin at time of enrollment

5. Willing to use Fiasp® insulin

6. Total daily insulin dose is at least 0.3 units/kg/day

7. Usual carbohydrate intake is at least 60 grams a day, and willing to have at least 25 grams of carbohydrates for breakfast

8. For females, not currently known to be pregnant

9. An understanding of and willingness to follow the protocol and sign the informed consent

10. Willing to have photographs taken of their infusion sites

11. Willing to download their 670G pump every 1-2 weeks to a research Carelink account

12. Willingness to answer a brief online questionnaire every 2 weeks

13. Must be able to understand spoken or written English

14. For subjects participating in Part 2 of this study they will need to be using Fiasp® as part of their usual care

15. Hemoglobin A1c between 6 and 10% at the time of enrollment

Exclusion Criteria:

1. Pregnant or lactating females

2. No hypoglycemic seizure or loss of consciousness in the past 6 months

3. Severe episode of DKA in the 6 months prior to study enrollment that was unrelated to an infusion set failure

4. No known cardiovascular events in the last 6 months

5. No active proliferative diabetic retinopathy

6. Known tape allergies

7. Current treatment for a seizure disorder

8. Cystic fibrosis

9. Active infection

10. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol

11. Inpatient psychiatric treatment in the past 6 months

12. Presence of a known adrenal disorder

13. If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, with lack of stability on the medication for the past 2 months prior to enrollment in the study

14. Abuse of alcohol

15. Dialysis or renal failure

16. Known eGFR <60%

Note: Adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94304
2	Stanford	Palo Alto	California	United States	94305

Sponsors and Collaborators

• Stanford University
• Medtronic

Investigators

• Principal Investigator: Bruce Buckingham, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 30, 2018

More Information

Publications

• Bode BW, Johnson JA, Hyveled L, Tamer SC, Demissie M. Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion. Diabetes Technol Ther. 2017 Jan;19(1):25-33. doi: 10.1089/dia.2016.0350. Epub 2017 Jan 5.
• Hsu L, Buckingham B, Basina M, Ekhlaspour L, von Eyben R, Wang J, Lal RA. Fast-Acting Insulin Aspart Use with the MiniMed(TM) 670G System. Diabetes Technol Ther. 2021 Jan;23(1):1-7. doi: 10.1089/dia.2020.0083.
• Zijlstra E, Demissie M, Graungaard T, Heise T, Nosek L, Bode B. Investigation of Pump Compatibility of Fast-Acting Insulin Aspart in Subjects With Type 1 Diabetes. J Diabetes Sci Technol. 2018 Jan;12(1):145-151. doi: 10.1177/1932296817730375. Epub 2017 Sep 18.

• Responsible Party: Bruce Buckingham, Professor of Pediatric Endocrinology, Stanford University
• ClinicalTrials.gov Identifier: NCT03554486
• Other Study ID Numbers: 46202
• First Posted: Jun 13, 2018
• Last Update Posted: Aug 18, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination

Study Results

Participant Flow

Pre-assignment Detail	27 participants signed informed consent. 3 participants failed screening and did not enter the run-in period (a 2-week period for pump-setting adjustments and monitoring).

Arm/Group Title	All Participants (run-in Period)	Fiasp Then Novolog	Novolog Then Fiasp
Arm/Group Description	Participants entered a 2-week run-in period prior to randomization.	Following randomization after a 2-week run-in period, participants use Fiasp insulin for 2 weeks, followed by Novolog insulin for 2 weeks.	Following randomization after a 2-week run-in period, participants use Novolog insulin for 2 weeks, followed by Fiasp insulin for 2 weeks.
Period Title: Run-in Period (2 Weeks)
STARTED	24	0	0
COMPLETED	21	0	0
NOT COMPLETED	3	0	0
Period Title: Run-in Period (2 Weeks)
STARTED	0	11	10
COMPLETED	0	10	9
NOT COMPLETED	0	1	1
Period Title: Run-in Period (2 Weeks)
STARTED	0	10	9
COMPLETED	0	10	9
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Fiasp Then Novolog	Novolog Then Fiasp	Total
Arm/Group Description	Following a 2-week run-in period, participants use Fiasp insulin for 2 weeks, followed by Novolog insulin for 2 weeks.	Following a 2-week run-in period, participants use Novolog insulin for 2 weeks, followed by Fiasp insulin for 2 weeks.	Total of all reporting groups
Overall Participants	10	9	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.0 (15.2)	44.1 (20.4)	40.4 (17.7)
Sex: Female, Male (Count of Participants)
Female	6 60%	3 33.3%	9 47.4%
Male	4 40%	6 66.7%	10 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	0 0%	1 5.3%
Not Hispanic or Latino	9 90%	9 100%	18 94.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 10%	0 0%	1 5.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	9 90%	9 100%	18 94.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	19 100%
Hemoglobin A1C (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated hemoglobin]	7.1 (0.9)	7.1 (0.5)	7.1 (0.7)

Outcome Measures

1. Primary Outcome

Title	Percentage of Time in Range: Sensor Glucose Values Between 70-180 mg/dl
Description	Measured as percentage of time in range (days).
Time Frame	7 days (during 2nd half of 2-week intervention period)

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Fiasp Insulin	Novolog Insulin
Arm/Group Description	Participants use Fiasp insulin for 2 weeks.	Participants use Novolog insulin for 2 weeks.
Measure Participants	19	19
Mean (Standard Deviation) [percentage of time]	78.4 (9.3)	75.3 (9.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp Insulin, Novolog Insulin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Percentage of Time in Range: Sensor Glucose Readings <70 mg/dl
Description	Percentage of time in range (days) as a measure of hypoglycemia.
Time Frame	7 days (during 2nd half of 2-week intervention period)

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Fiasp Insulin	Novolog Insulin
Arm/Group Description	Participants use Fiasp insulin for 2 weeks.	Participants use Novolog insulin for 2 weeks.
Measure Participants	19	19
Mean (Standard Deviation) [percentage of time]	2.3 (2.0)	3.1 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp Insulin, Novolog Insulin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Mean Sensor Glucose in mg/dl
Description	Mean sensor data over the second week of using a randomized, blinded insulin.
Time Frame	7 days (during 2nd half of 2-week intervention period)

Outcome Measure Data

Analysis Population Description

Participants who completed the protocol are included in the analysis.

Arm/Group Title	Fiasp Insulin	Novolog Insulin
Arm/Group Description	Participants use Fiasp insulin for 2 weeks.	Participants use Novolog insulin for 2 weeks.
Measure Participants	19	19
Mean (Standard Deviation) [mg/dL]	146 (12)	147 (12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp Insulin, Novolog Insulin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Run-in Period		Fiasp Insulin		Novolog Insulin
Arm/Group Description	Participants with events occurring prior to randomization.		Participants with events occurring during Fiasp insulin treatment.		Participants with events occurring during Novolog insulin treatment.
All Cause Mortality
	Run-in Period		Fiasp Insulin		Novolog Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/19 (0%)		0/19 (0%)
Serious Adverse Events
	Run-in Period		Fiasp Insulin		Novolog Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/19 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Infusion set failure	0/28 (0%)		0/19 (0%)		1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Run-in Period		Fiasp Insulin		Novolog Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/19 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Irritation/Inflammation	0/28 (0%)		0/19 (0%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.