Diabetes Mellitus, Type 1Phase 2DualNCT03800875
Insulin-plus-pramlintide Closed-loop Strategy to Regulate Glucose Levels Without Carbohydrate Counting
A Phase 2 study testing 27-hour inpatient intervention in people with Diabetes Mellitus, Type 1, run by McGill University at 1 site in Canada.
Trial summary
Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- 27-hour inpatient intervention
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 8 Feb 2019to 19 Sep 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females ≥ 18 years of age.
- Clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
- Insulin pump therapy for at least 6 months.
- HbA1c ≤ 12% in the last 6 months.
Who cannot join
- Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc.…).
- Severe hypoglycemic episode within one month of admission.
- Severe diabetic ketoacidosis episode within one month of admission.
- Pregnancy.
- Known or suspected allergy to the study drugs.
- Gastroparesis.
Show all 12Show fewer
- Use of prokinetic drugs that stimulate gastric emptying (domperidone, cisapride, metoclopramide).
- Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
- Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
- Current use of glucocorticoid medication.
- Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
- Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Controlled, Crossover Trial to Assess a Dual-hormone (Insulin-pramlintide) Closed-loop Delivery Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes
Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user.
Read the detailed description
Meal carbohydrate content is the main determinant of prandial insulin needs, and consequently, accurate carbohydrate counting is recommended for type 1 diabetes. Advances in glucose sensors have motivated the development of the closed-loop system to automatically regulate glucose levels in individuals with type 1 diabetes. In the closed-loop system, a dosing algorithm adjusts the pump insulin infusion rate based on continuous glucose sensor readings.
Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user. Thus, the two hormones' role in the postprandial state will be as follows:
- Insulin: to reduce plasma glucose levels. Insulin delivery needs to be aggressive to counter-act fast increase in post-meal glucose levels.
- Pramlintide: to slow gastric emptying and aim insulin in efficiently controlling postprandial glucose levels.
The aim of this study is to assess a fully automated, dual-hormone, closed-loop system that delivers insulin, and pramlintide to control glucose levels without degrading overall glycemic control compared to an insulin-alone closed-loop system with carbohydrate-matched boluses.
The investigators hypothesize that the dual-hormone closed-loop system will alleviate carbohydrate-counting burden (fully reactive system) without degrading glucose control compared to the insulin-alone closed-loop system.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- 27-hour inpatient intervention
- Keywords
- Diabetes Mellitus, Type 1, Pramlintide, Insulin, Dual-Hormone, Closed-Loop, Artificial Pancreas
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
27-hour inpatient interventionDrug
Subjects will be admitted at the research facility at 19:00. Each 27-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (22:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The infusion rate of either insulin alone or insulin and pramlintide will be changed manually based on the computer generated recommendation. The computer generated recommendations are based on a predictive algorithm.
| Study group | Role | What they receive |
|---|---|---|
| Insulin-Pramlintide Closed-Loop Strategy | Experimental | Fast-acting insulin will be delivered using two separate infusion pumps. The pumps' infusion rates will then be changed manually based on the computer-generated recommendation. The computer-generated recommendations are based on a dosing algorithm. With no-meal announcement or carbohydrate counting, the dual-hormone closed-loop system will be fully reactive, and insulin and pramlintide dosages will be based solely on sensor readings Receives: Drug: 27-hour inpatient intervention |
| Insulin-alone Closed Loop Strategy | Active comparator | Fast-acting insulin will be delivered by a subcutaneous insulin infusion pump based on an algorithm that automatically adjusts insulin rates based on a dosing algorithm. The carbohydrate content for every ingested meal will be entered into the algorithm to calculate the insulin prandial bolus based on each participant's insulin-to-carbohydrate ratio. The carbohydrate content will be entered at the onset of the meal.
Drug(s): Insulin (FiAsp) Receives: Drug: 27-hour inpatient intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L
Measured: 24 hours
Secondary outcomes (10)
Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges.
- between 3.9 and 7.8 mmol/L; b. below 3.9 mmol/L; c. between 3.9 and 10 mmol/L d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L.
Measured: 24 hours
Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.
- between 3.9 and 7.8 mmol/L; b. between 3.9 and 10 mmol/L; c. below 3.9 mmol/L; d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L.
Measured: 8 hours
Total amount of insulin delivered to the participant
Measured: 24 hours
Mean sensor glucose concentration during the overnight stay
Measured: 8 hours
Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day
Measured: 27 hours
The number and severity of gastrointestinal sysmptoms experienced by a participant
GI symptoms include: nausea, vomiting, bloating and heartburn
Measured: 27 hours
Mean daytime insulin concentration
Measured: 14 hours
Mean daytime concentration of amylin
Measured: 14 hours
Total amount of pramlintide delivered to the participant
Measured: 24 hours
Mean glucose level
Measured: 24-hour period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start8 Feb 2019
- Primary completion19 Sep 2020
- Study completion19 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University
- Sponsor type
- University, hospital or other
- Collaborators
- Diabetes Canada
- Responsible party
- Sponsor
- Investigators
- Michael Tsoukas, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03800875
- Sponsor's protocol ID
- Triple Hormone
- Acronym
- Dual
- Status last verified
- Jun 2021
- First submitted
- 27 Jun 2018
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The raw data (i.e., insulin delivery, glucose levels, individual participant data) and informed consent form could be shared by the corresponding author, ahmad.haidar@mcgill.ca, upon reasonable request for academic purposes, subject to Material Transfer Agreement and approval of McGill University Health Center's Research Ethics Board. All data shared will be de-identified. The study protocol will be available with publication.
Publications
Tsoukas MA, Majdpour D, Yale JF, Fathi AE, Garfield N, Rutkowski J, Rene J, Legault L, Haidar A. A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. Lancet Digit Health. 2021 Nov;3(11):e723-e732. doi: 10.1016/S2589-7500(21)00139-4. Epub 2021 Sep 24.
PubMed 34580055
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Crossover Trial to Assess a Dual-hormone (Insulin-pramlintide) Closed-loop Delivery Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03800875
- Acronym / sponsor ID
- Dual / Triple Hormone
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes Mellitus, Type 1, Pramlintide, Insulin, Dual-Hormone, Closed-Loop, Artificial Pancreas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- McGill UniversityUniversity, hospital or other
- Collaborators
- Diabetes Canada
- Study start
- 8 Feb 2019 (actual)
- Primary completion
- 19 Sep 2020 (actual)
- Study completion
- 19 Sep 2020 (actual)
- First posted
- 11 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user.
Detailed description
Meal carbohydrate content is the main determinant of prandial insulin needs, and consequently, accurate carbohydrate counting is recommended for type 1 diabetes. Advances in glucose sensors have motivated the development of the closed-loop system to automatically regulate glucose levels in individuals with type 1 diabetes. In the closed-loop system, a dosing algorithm adjusts the pump insulin infusion rate based on continuous glucose sensor readings.
Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user. Thus, the two hormones' role in the postprandial state will be as follows:
- Insulin: to reduce plasma glucose levels. Insulin delivery needs to be aggressive to counter-act fast increase in post-meal glucose levels.
- Pramlintide: to slow gastric emptying and aim insulin in efficiently controlling postprandial glucose levels.
The aim of this study is to assess a fully automated, dual-hormone, closed-loop system that delivers insulin, and pramlintide to control glucose levels without degrading overall glycemic control compared to an insulin-alone closed-loop system with carbohydrate-matched boluses.
The investigators hypothesize that the dual-hormone closed-loop system will alleviate carbohydrate-counting burden (fully reactive system) without degrading glucose control compared to the insulin-alone closed-loop system.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin-Pramlintide Closed-Loop Strategy | Experimental | Drug: 27-hour inpatient interventionFast-acting insulin will be delivered using two separate infusion pumps. The pumps' infusion rates will then be changed manually based on the computer-generated recommendation. The computer-generated recommendations are based on a dosing algorithm. With no-meal announcement or carbohydrate counting, the dual-hormone closed-loop system will be fully reactive, and insulin and pramlintide dosages will be based solely on sensor readings |
| Insulin-alone Closed Loop Strategy | Active comparator | Drug: 27-hour inpatient interventionFast-acting insulin will be delivered by a subcutaneous insulin infusion pump based on an algorithm that automatically adjusts insulin rates based on a dosing algorithm. The carbohydrate content for every ingested meal will be entered into the algorithm to calculate the insulin prandial bolus based on each participant's insulin-to-carbohydrate ratio. The carbohydrate content will be entered at the onset of the meal. Drug(s): Insulin (FiAsp) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females ≥ 18 years of age.
- Clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
- Insulin pump therapy for at least 6 months.
- HbA1c ≤ 12% in the last 6 months.
Key exclusion criteria (12 listed)
- Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc.…).
- Severe hypoglycemic episode within one month of admission.
- Severe diabetic ketoacidosis episode within one month of admission.
- Pregnancy.
- Known or suspected allergy to the study drugs.
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 |
|---|---|---|
| 27-hour inpatient interventionSubjects will be admitted at the research facility at 19:00. Each 27-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (22:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The infusion rate of either insulin alone or insulin and pramlintide will be changed manually based on the computer generated recommendation. The computer generated recommendations are based on a predictive algorithm. | Drug | Insulin-Pramlintide Closed-Loop Strategy, Insulin-alone Closed Loop Strategy |
Primary outcome
Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L
Time frame: 24 hours
10 secondary outcomes
Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges.
Time frame: 24 hours
Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.
Time frame: 8 hours
Total amount of insulin delivered to the participant
Time frame: 24 hours
Mean sensor glucose concentration during the overnight stay
Time frame: 8 hours
Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day
Time frame: 27 hours
The number and severity of gastrointestinal sysmptoms experienced by a participant
Time frame: 27 hours
Mean daytime insulin concentration
Time frame: 14 hours
Mean daytime concentration of amylin
Time frame: 14 hours
Total amount of pramlintide delivered to the participant
Time frame: 24 hours
Mean glucose level
Time frame: 24-hour period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Derived from this study: PubMed 34580055Tsoukas MA, Majdpour D, Yale JF, Fathi AE, Garfield N, Rutkowski J, Rene J, Legault L, Haidar A. A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. Lancet Digit Health. 2021 Nov;3(11):e723-e732. doi: 10.1016/S2589-7500(21)00139-4. Epub 2021 Sep 24.
- Individual participant dataSharing planned: Yes. The raw data (i.e., insulin delivery, glucose levels, individual participant data) and informed consent form could be shared by the corresponding author, ahmad.haidar@mcgill.ca, upon reasonable request for academic purposes, subject to Material Transfer Agreement and approval of McGill University Health Center's Research Ethics Board. All data shared will be de-identified. The study protocol will be available with publication.
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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.
Michael Tsoukas principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 27-hour inpatient intervention in people with Diabetes Mellitus, Type 1, run by McGill University at 1 site in Canada.
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 4 inclusion and 12 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 8 Jun 2021. 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 Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03800875, which also lists 1 linked publication.
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 8 Jun 2021.