Type 1 DiabetesPhase 1NCT04416737
Evaluating the Benefits of Physiologic Insulin Delivery
A Phase 1 study testing Ultra-rapid insulin in people with Type 1 Diabetes, run by Stanford University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Ultra-rapid insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2021to 2 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18-60 years of age
- Clinical diagnosis of type 1 diabetes
- On insulin pump therapy and continuous glucose monitor (CGM) for at least 3 months
- Ability to safely receive intraperitoneal injection
- For females, not currently known to be pregnant
- Understanding and willingness to follow the protocol and sign informed consent
- Ability to speak, read and write in the language of the investigators
Who cannot join
- Diabetic ketoacidosis in the past 3 months
- Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
- Pregnant or lactating
- Active infection
- A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol
- Known cardiovascular events in the last 6 months
Show all 11Show fewer
- Known seizure disorder
- Inpatient psychiatric treatment in the past 6 months
- Lack of stability on medication 1 month prior to enrollment including antihypertensive, thyroid, anti-depressant or lipid lowering medication.
- Suspected drug or alcohol abuse
- Chronic kidney disease (GFR < 60 mL/min/1.73m^2)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Ultra-rapid insulin
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultra-rapid insulinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ultra-rapid insulin |
| 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. Receives: Drug: Ultra-rapid insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Secondary outcomes (3)
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).
Measured: 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).
Measured: 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).
Measured: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start1 Nov 2021
- Primary completion2 Jun 2023
- Study completion2 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rayhan A. Lal, Stanford University
- Investigators
- Rayhan Lal, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04416737
- Sponsor's protocol ID
- IRB-57032
- Other IDs
- 1K23DK122017
- Status last verified
- Sep 2024
- First submitted
- 2 Jun 2020
- Last updated
- 1 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No current plan
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Benefits of Physiologic Insulin Delivery
- ClinicalTrials.gov ID
- NCT04416737
- Acronym / sponsor ID
- IRB-57032
- Conditions
- Type 1 Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 2 Jun 2023 (actual)
- Study completion
- 2 Jun 2023 (actual)
- First posted
- 4 Jun 2020 (actual)
- Results
- Posted 1 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Upper Peritoneal, then Lower Peritoneal, then Subcutaneous | Experimental | Drug: Ultra-rapid insulinUltra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space. |
| Lower Peritoneal, then Upper Peritoneal, then Subcutaneous | Experimental | Drug: Ultra-rapid insulinUltra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 18-60 years of age
- Clinical diagnosis of type 1 diabetes
- On insulin pump therapy and continuous glucose monitor (CGM) for at least 3 months
- Ability to safely receive intraperitoneal injection
- For females, not currently known to be pregnant
Key exclusion criteria (11 listed)
- Diabetic ketoacidosis in the past 3 months
- Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
- Pregnant or lactating
- Active infection
- A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ultra-rapid insulinFollowing 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. | Drug | Lower Peritoneal, then Upper Peritoneal, then Subcutaneous, Upper Peritoneal, then Lower Peritoneal, then Subcutaneous |
Primary outcome
Glucagon Response to Induced Hypoglycemia
Time frame: 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.
3 secondary outcomes
Insulin Maximum Concentration in Plasma
Time frame: 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
Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Time Until Maximum Insulin Concentration in Plasma
Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No current plan
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rayhan Lal, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ultra-rapid insulin in people with Type 1 Diabetes, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucagon Response to Induced Hypoglycemia (time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.