Evaluating the Benefits of Physiologic Insulin Delivery

Phase 1

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: Ultra-rapid insulin

• Registration Number: NCT04416737
• Lead Sponsor: Stanford University

Brief Summary

In normal physiology insulin is secreted by beta cells into the portal vein. There have been a number of purported benefits among long-term intraperitoneal insulin users. In the present study we will inject ultra-rapid acting insulin into the upper and lower peritoneum under ultrasound guidance and compare it to subcutaneous injection. We will measure glucose, insulin and glucagon following these injections, to assess for benefits in counter-regulatory hormone production and insulin pharmacokinetics.

Detailed Description

The eventual goal of this line of work is an implanted insulin pump that delivers insulin automatically into the peritoneum based on continuous glucose data. All prior intraperitoneal pharmacokinetic studies used only concentrated regular insulin, which may be too slow to provide full closed-loop insulin delivery without meal announcement. A description of intraperitoneal ultra-rapid insulin kinetics, as well as counter-regulatory hormonal factors that may counter hypoglycemia is needed. Upper versus lower peritoneal delivery may also affect insulin kinetics. A possible benefit of intraperitoneal insulin is restoration of glucagon response in longstanding diabetes and clearance of insulin by the liver, both of which could provide hypoglycemic rescue in automated insulin delivery systems.

Study Timeline

• Study First Submitted: 2020-06-02
• Study First Submitted QC: 2020-06-02
• Study First Posted: 2020-06-04
• Study Start: 2021-11-01
• Primary Completion: 2023-06-02
• Study Completion: 2023-06-02
• Results First Submitted: 2024-06-02
• Status Verified: 2024-09
• Results First Submitted QC: 2024-09-05
• Last Update Submitted: 2024-09-05
• Results First Posted: 2024-10-01
• Last Update Posted: 2024-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. 18-60 years of age
2. Clinical diagnosis of type 1 diabetes
3. On insulin pump therapy and continuous glucose monitor (CGM) for at least 3 months
4. Ability to safely receive intraperitoneal injection
5. For females, not currently known to be pregnant
6. Understanding and willingness to follow the protocol and sign informed consent
7. Ability to speak, read and write in the language of the investigators

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Exclusion Criteria

1. Diabetic ketoacidosis in the past 3 months
2. Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
3. Pregnant or lactating
4. Active infection
5. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol
6. Known cardiovascular events in the last 6 months
7. Known seizure disorder
8. Inpatient psychiatric treatment in the past 6 months
9. Lack of stability on medication 1 month prior to enrollment including antihypertensive, thyroid, anti-depressant or lipid lowering medication.
10. Suspected drug or alcohol abuse
11. Chronic kidney disease (GFR < 60 mL/min/1.73m^2)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Upper Peritoneal, then Lower Peritoneal, then Subcutaneous	Ultra-rapid insulin	Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.
Lower Peritoneal, then Upper Peritoneal, then Subcutaneous	Ultra-rapid insulin	Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.

Primary Outcome Measures

Name	Time	Method
Glucagon Response to Induced Hypoglycemia	Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max	For each injection site we will assess the peak concentration of glucagon at time of the first induced hypoglycemic nadir.; Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).; Participants must have achieved induced hypoglycemia to be evaluable for the primary outcome.

Secondary Outcome Measures

Name	Time	Method
Insulin Maximum Concentration in Plasma	Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max	We will assess the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight).; Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).
Hypoglycemic Treatments Required as a Measure of Glucose Values	Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max	We will compare the number of rescue treatments (2.5ml/kg 10% Dextrose) required to treat hypoglycemia \<50mg/dl for each injection location of approximately 0.25u/kg ultra-rapid insulin.; Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).
Time Until Maximum Insulin Concentration in Plasma	Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max	We will assess time until the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight).; Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States