Hybrid Closed Loop Insulin Delivery System in Hypoglycemia

NCT03215914 | Completed Results DMC FDA Device

• 2 other identifiers: 8275572R01DK091331
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

Can a type 1 diabetic adult avoid low glucoses and regain hypoglycemia awareness using a hybrid closed loop insulin delivery system? Involvement is 22 months (13 visits) and includes a 4-week Screening Phase and an 18-month Intervention Phase. Participants will undergo 3 Hyperinsulinemic Clamps done at: Baseline (before starting the device and after completing the screening), 6 months (after using the device 6 months), and after using the device for 18 months. This metabolic testing will allow us to measure improvement in hypoglycemia awareness.

Conditions

Type1diabetes; Hypoglycemia Unawareness; Nocturnal Hypoglycemia; Hypoglycemia Night; Hypoglycemia

Keywords

Closed loop insulin delivery system; Insulin Pump; Glycemic control; Glucose Counterregulation

Outcome Measures

Primary Outcomes (1)

• Endogenous Glucose Production

  The primary outcome measure will be endogenous glucose production in response to insulin-induced hypoglycemia.

  After 6 months of hybrid closed-loop insulin delivery.

Secondary Outcomes (1)

• Endogenous Glucose Production

  After 18 months of hybrid closed-loop insulin delivery.

Study Arms (1)

Subjects with type 1 diabetes using MiniMed 670G system

EXPERIMENTAL

Eligible subjects with type 1 diabetes will initiate hybrid closed-loop insulin delivery based on interstitial glucose monitoring via the MiniMed 670G system according to Medtronic's labeling. This system combines subject-delivered pre-meal boluses with automatic interprandial insulin delivery that includes automated functions for both predictive and threshold suspension of insulin delivery intended to minimize exposure to glucose levels \< 70 mg/dl.

Device: MiniMed 670G system

Interventions

MiniMed 670G system DEVICE

Eligible subjects with type 1 diabetes will initiate hybrid closed-loop insulin delivery based on interstitial glucose monitoring via the MiniMed 670G system according to Medtronic's labeling. This system combines subject-delivered pre-meal boluses with automatic interprandial insulin delivery that includes automated functions for both predictive and threshold suspension of insulin delivery intended to minimize exposure to glucose levels \< 70 mg/dl.

Subjects with type 1 diabetes using MiniMed 670G system

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects age 25 to 70 years.
• Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
• Clinical history compatible with type 1 diabetes with disease onset \< 40 years of age and insulin dependent for \> 10 years.
• Absent C-peptide (\< 0.3 ng/ml).
• Involvement in intensive diabetes management defined as the use of basal-bolus insulin analog delivery by multi-dose injection (MDI) or continuous subcutaneous insulin infusion (CSII) together with self-monitoring of blood glucose values more than 3 times daily with or without continuous glucose monitoring (CGM) under the direction of an endocrinologist, diabetologist, or diabetes nurse practitioner with at least 3 clinical evaluations during the previous 12 months.
• Hypoglycemia unawareness manifested by a Clarke score of 4 or more AND at least 1 of the following: HYPO score greater than or equal to the 90th percentile (1047); OR marked glycemic lability defined by a glycemic lability index (LI) score greater than or equal to the 90th percentile (433 mmol/l2/h•wk-1); OR a composite of a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) (Senior et al., 2015).
• Documented \> 5% time spent in the hypoglycemic range (glucose \< 60 mg/dl) by 7 day real- time or blinded CGM; at least one episode of hypoglycemic during the 7 days must occur overnight.

You may not qualify if:

• BMI ≥ 30 kg/m2.
• Insulin requirement of ≥ 1.0 units/kg•day.
• HbA1c ≥ 10%.
• Untreated proliferative diabetic retinopathy.
• Uncontrolled hypertension: systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.
• Active cardiovascular disease
• Abnormal kidney function: eGFR \< 60 ml/min/1.73 m2.
• Abnormal liver function: persistent elevation of liver function tests \> 1.5 times the upper limit of normal.
• Untreated hypothyroidism, Addison's disease, or Celiac disease.
• Anemia: baseline hemoglobin concentration \< 11 g/dl in women and \< 12 g/dl in men.
• Presence of a seizure disorder not related to prior severe hypoglycemia.
• Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone.
• For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
• Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
• Use of any investigational agents within 4 weeks of enrollment.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (3)

Clinical and Translational Research Center, Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rodebaugh Diabetes Center, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania - Institute for Diabetes, Obesity and Metabolism

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Malone SK, Matus AM, Flatt AJ, Peleckis AJ, Grunin L, Yu G, Jang S, Weimer J, Lee I, Rickels MR, Goel N. Prolonged Use of an Automated Insulin Delivery System Improves Sleep in Long-Standing Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia. J Diabetes Sci Technol. 2024 Nov;18(6):1416-1423. doi: 10.1177/19322968231182406. Epub 2023 Jul 14.

  PMID: 37449426 DERIVED

• Malone SK, Peleckis AJ, Grunin L, Yu G, Jang S, Weimer J, Lee I, Rickels MR, Goel N. Characterizing Glycemic Control and Sleep in Adults with Long-Standing Type 1 Diabetes and Hypoglycemia Unawareness Initiating Hybrid Closed Loop Insulin Delivery. J Diabetes Res. 2021 Feb 12;2021:6611064. doi: 10.1155/2021/6611064. eCollection 2021.

  PMID: 33628834 DERIVED

Related Links

• Institute for Diabetes, Obesity and Metabolism Research Studies
• Research Studies at the University of Pennsylvania
• Perelman School of Medicine / Faculty Search / Michael Rickels, M.D., M.S

MeSH Terms

Conditions

Hypoglycemia

Interventions

Drug Delivery Systems

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Results Point of Contact

• Title: Cornelia V. Dalton Bakes
• Organization: University of Pennsylvania

corneliv@pennmedicine.upenn.edu

215-746-2085

Study Officials

• Michael R Rickels, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: No masking.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Open label, single-arm trial of the effect of hybrid closed-loop insulin delivery on glucose counterregulatory mechanisms assessed by the stepped- hyperinsulinemic hypoglycemic clamp in patients with long standing type 1 diabetes complicated by hypoglycemia unawareness.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 12, 2017
• Study Start: August 1, 2017
• Primary Completion: May 31, 2022
• Study Completion: October 1, 2024
• Last Updated: October 24, 2024
• Results First Posted: September 28, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Immediately
• Access Criteria: To request an informed consent document please contact: Ginger Bakes, CCRC: Cornelia.dalton-bakes@uphs.upenn.edu

Locations

US (3)