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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23DK122017 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Upper Peritoneal, then Lower Peritoneal, then Subcutaneous | Experimental | Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space. |
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| Lower Peritoneal, then Upper Peritoneal, then Subcutaneous | Experimental | Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ultra-rapid insulin | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Glucagon Response to Induced Hypoglycemia | 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. | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Maximum Concentration in Plasma | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rayhan Lal, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94304 | United States |
No current plan
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| ID | Title | Description |
|---|---|---|
| FG000 | Upper Peritoneal, Then Lower Peritoneal, Then Subcutaneous | Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space. |
| FG001 | Lower Peritoneal, Then Upper Peritoneal, Then Subcutaneous | Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 1 (First Injection) |
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| Week 2 (Second Injection) |
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| Week 3 (Third Injection) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Upper Peritoneal, Then Lower Peritoneal, Then Subcutaneous | Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space. |
| BG001 | Lower Peritoneal, Then Upper Peritoneal, Then Subcutaneous |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Glucagon Response to Induced Hypoglycemia | 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. | Participants with successfully induced hypoglycemia at the respective study visit | Posted | Median | Inter-Quartile Range | pg/mL | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max | Injections | Injections |
|
Average approximately 2 months (may have been up to 13 months).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Upper Peritoneal Injection | Ultra-fast acting insulin injected into the upper peritoneum |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rayhan Lal | Stanford University | 650-725-2908 | inforay@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 14, 2022 | May 29, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 14, 2022 | Jun 5, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Participants will each come in for 3 visits separated by at least 1 week. During the first two visits they will be randomized to either upper or lower peritoneal injection followed by the other site. During the third visit a subcutaneous injection will be performed to provide comparative data to the standard of care.
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| Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max |
| Hypoglycemic Treatments Required as a Measure of Glucose Values | 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). | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max |
| Time Until Maximum Insulin Concentration in Plasma | 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). | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max |
| Achieved Induced Hypoglycemia |
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| COMPLETED |
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| NOT COMPLETED |
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| Achieved Induced Hypoglycemia |
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| COMPLETED |
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| NOT COMPLETED |
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Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Lower Peritoneal Injection |
Ultra-fast acting insulin injected into the lower peritoneum |
| OG002 | Injection- All Peritoneal | Ultra-fast acting insulin injected into the peritoneum |
| OG003 | Subcutaneous Injection | Ultra-fast acting insulin injected subcutaneously |
|
|
| Secondary | Insulin Maximum Concentration in Plasma | 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). | Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours. | Posted | Median | Inter-Quartile Range | mU/L | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max | Injections | Injections |
|
|
|
| Secondary | Hypoglycemic Treatments Required as a Measure of Glucose Values | 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). | Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours. | Posted | Median | Inter-Quartile Range | Treatments | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max | Injections | Injections |
|
|
|
| Secondary | Time Until Maximum Insulin Concentration in Plasma | 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). | Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours. | Posted | Median | Inter-Quartile Range | minutes | Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max | Injections | Injections |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Lower Peritoneal Injection | Ultra-fast acting insulin injected into the lower peritoneum | 0 | 16 | 0 | 16 | 0 | 16 |
| EG002 | Subcutaneous Injection | Ultra-fast acting insulin injected subcutaneously | 0 | 15 | 0 | 15 | 0 | 15 |
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Injections |
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| Injections |
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| Injections |
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