Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin in Patients With Type 1 Diabetes on Multiple Daily Injections: Investigator-Initiated A Real-life Pilot Study-STAT Study

NCT ID: NCT03143816

Last Updated: 2022-02-22

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-30

Study Completion Date

2018-01-31

Brief Summary

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This is an investigator-initiated, prospective, randomized, multicenter, parallel, open-label, pilot clinical trial evaluating the efficacy of TI for PPBG, PPGE, and time-in-range on CGM download in patients with T1D. TI is an inhaled ultra-rapid-acting insulin, approved by the FDA for use in patients with diabetes. This is a pilot, real-life study where patients will continue their routine diabetes care and use post-meal correction dosages as deemed necessary for normalizing PPBG as per the protocol.

This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

All patients will use real-time CGM (Dexcom G5®, San Diego, CA), which will be provided at the randomization visit for their day-to-day diabetes care. CGM data will be downloaded at every clinic visit on a secured computer. The data will be analyzed after the study for different primary and secondary end points. All patients will be allowed to keep the CGM after the study is over for their day-to-day diabetes care.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Technosphere insulin (TI, Afrezza) -Treatment arm

Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG ( post prandial blood glucose)

Group Type ACTIVE_COMPARATOR

Technosphere insulin

Intervention Type DRUG

This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

Insulin Aspart ( Novolog) -Control arm

Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Technosphere insulin

This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent before any study-related activities,
2. Male or female aged 18-70 years,
3. Type 1 diabetes mellitus (T1D) duration more than six months
4. Treatment with multiple daily injections (MDI) for at least three months before screening visit; stable insulin dose for the last one month,
5. No use of any oral anti-diabetics, any other form of insulin other than mentioned in the protocol, or any other type of injections such as glucagon-like-peptide-1 (GLP-1) analogs, pramlintide or insulin/GLP-1 analog combinations,
6. A1c between 6.5 to 10%,
7. Willingness to routinely collect at least two blood glucose measurements per day needed to calibrate the CGM. Beyond the calibrations, patients may use CGM for necessary action without having to confirm with fingersticks self-monitoring blood glucose (SMBG), as approved by the Food and Drug Administration (FDA),
8. BMI ≤35 kg/m2,
9. Ability and willingness to adhere to the protocol including clinical and phone visits and 4-week-long CGM wear,
10. Using insulin glargine or insulin degludec as basal insulin,
11. Able to use and understand CGM data,
12. Willing to complete phone and clinic visits,
13. Patients who eat three main meals in a day (breakfast, lunch, and dinner),
14. Patients who use insulin-carb ratio for bolus,
15. Ability to speak, read, and write English, and
16. Patients prandial insulin need must be \<18 units per meal

Exclusion Criteria

1. Use of any other diabetic medication other than allowed in the protocol,
2. Pregnant or intention to become pregnant during the study, or not using adequate birth control methods,
3. Severe unexplained hypoglycemia requiring emergency treatment in the previous three months,
4. Use of systemic or inhaled corticosteroids,
5. History of hemoglobinopathies,
6. Diagnosis of anemia,
7. Post-renal transplantation, currently undergoing dialysis, creatinine \>2.0 mg/dl or a calculated creatinine clearance of \<50 mL/min,
8. Advanced or unstable retinopathy needing laser procedure or vitrectomy,
9. History of pancreatitis,
10. Extensive skin changes/diseases that inhibit wearing a sensor on normal skin,
11. Known allergy to adhesives,
12. Known allergy to study medication,
13. Participation in another investigational study protocol within 30 days before enrollment,
14. Known chronic obstructive pulmonary disease, pulmonary hypertension, asthma, pulmonary fibrosis, or any chronic pulmonary infection, or any systemic disease that primarily affects the lungs. History of any pulmonary nodule will be excluded to participate in the study,
15. Active smokers,
16. Marijuana users,
17. Insulin pump users,
18. Using insulin detemir or NPH as basal insulin, and
19. Any other condition, as determined by the investigator, which could make the subject unsuitable for the trial, impairs the subject's suitability for the trial, or impairs the validity of the informed consent -
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Atlanta Diabetes Associates

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role collaborator

Rainier Clinical Research Center

OTHER

Sponsor Role collaborator

Mannkind Corporation

INDUSTRY

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Barbara Davis Center

Aurora, Colorado, United States

Site Status

Countries

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United States

References

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1. Rathbone M, Hadgraft J, Roberts M, Lane M, Leone-Bay A, Grant M. Technosphere/insulin: mimicking endogenous insulin release. In Modified-Release Drug Delivery Technology. Vol. 2, 2nd ed. Rathbone M, Hadgraft J, Roberts M, Lane M, Eds. New York, Informa Healthcare USA, Inc., 2008, p. 673-679

Reference Type BACKGROUND

Richardson PC, Boss AH. Technosphere insulin technology. Diabetes Technol Ther. 2007 Jun;9 Suppl 1:S65-72. doi: 10.1089/dia.2007.0212.

Reference Type BACKGROUND
PMID: 17563306 (View on PubMed)

https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf, April 2017

Reference Type BACKGROUND

Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB; Affinity 1 Study Group. Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial. Diabetes Care. 2015 Dec;38(12):2266-73. doi: 10.2337/dc15-0075. Epub 2015 Jul 15.

Reference Type BACKGROUND
PMID: 26180109 (View on PubMed)

Rosenstock J, Lorber DL, Gnudi L, Howard CP, Bilheimer DW, Chang PC, Petrucci RE, Boss AH, Richardson PC. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010 Jun 26;375(9733):2244-53. doi: 10.1016/S0140-6736(10)60632-0.

Reference Type BACKGROUND
PMID: 20609970 (View on PubMed)

Skyler JS, Weinstock RS, Raskin P, Yale JF, Barrett E, Gerich JE, Gerstein HC; Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005 Jul;28(7):1630-5. doi: 10.2337/diacare.28.7.1630.

Reference Type BACKGROUND
PMID: 15983312 (View on PubMed)

Garg SK, Kelly W, Freson B, Ritchie P. Treat-to-target technosphere insulin study in adult subjects with type 1 diabetes. Poster presented at American Diabetes Association 2011 annual meeting.

Reference Type BACKGROUND

Akturk HK, Snell-Bergeon JK, Rewers A, Klaff LJ, Bode BW, Peters AL, Bailey TS, Garg SK. Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study. Diabetes Technol Ther. 2018 Oct;20(10):639-647. doi: 10.1089/dia.2018.0200. Epub 2018 Sep 15.

Reference Type DERIVED
PMID: 30207748 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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17-0427

Identifier Type: -

Identifier Source: org_study_id

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