Evaluating the Benefits of Physiologic Insulin Delivery

Stanford University

Status and phase: Completed; Phase 1

Conditions: Type 1 Diabetes

Treatments: Drug: Ultra-rapid insulin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04416737

1K23DK122017 (U.S. NIH Grant/Contract)

IRB-57032

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Upper Peritoneal, then Lower Peritoneal, then Subcutaneous

Experimental group

Description:

Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.

Treatment:

Drug: Ultra-rapid insulin

Lower Peritoneal, then Upper Peritoneal, then Subcutaneous

Experimental group

Description:

Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.

Treatment:

Drug: Ultra-rapid insulin