Evaluating the Benefits of Physiologic Insulin Delivery

NCT ID: NCT04416737

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2023-06-02

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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Upper Peritoneal, then Lower Peritoneal, then Subcutaneous

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

Group Type: EXPERIMENTAL

Ultra-rapid insulin

Intervention Type: DRUG

Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.

Lower Peritoneal, then Upper Peritoneal, then Subcutaneous

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

Group Type: EXPERIMENTAL

Ultra-rapid insulin

Intervention Type: DRUG

Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.

Interventions

Ultra-rapid insulin

Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Rayhan A. Lal

Med+Peds Endocrinologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rayhan Lal, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1K23DK122017

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-57032

Identifier Type: -

Identifier Source: org_study_id