Type 1 Diabetes MellitusNCT03709108
Safety and Feasibility of an Insulin Sensitivity-Informed Bolus Calculator in Type 1 Diabetes
A study testing SI-Informed Bolus Calculator in people with Type 1 Diabetes Mellitus, run by University of Virginia at 1 site in United States.
Trial summary
This is a single-center randomized crossover trial. The investigators will target completion of 15 adults (age 18-65 years) with Type 1 Diabetes who use an insulin pump. After completion of the Screening Visit, each subject will participate in a 28-day at home Data Collection Period while using their personal insulin… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- SI-Informed Bolus Calculator
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2018to 31 Mar 2019
- Phase
- Interventional
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes for at least 12 months
- Current use of an insulin pump for at least 12 months
- Current or historical use of a CGM system for at least 6 months
- Age ≥18 to ≤65 years old
- HbA1c <8.5% at screening; if HbA1c <6.0% then total daily insulin must be ≥0.5 U/kg
- For females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study
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- Willingness to use the same set of insulin therapy parameters (i.e., basal rate, insulin-to-carbohydrate ratio, correction factor) during both admissions
- Willingness to upload data during the study
- An understanding of and willingness to follow the protocol and sign the informed consent
Who cannot join
- Diabetes ketoacidosis (DKA) in the 6 months prior to enrollment
- Clinically significant electrocardiogram (ECG) found at Screening as determined by the study medical physician
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment
- Currently being treated for a seizure disorder
- Coronary artery disease or heart failure, unless written clearance is received from a cardiologist or primary care provider and documentation of a negative stress test within the year
- History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
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- Cystic fibrosis
- Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures
- Abnormal liver function test results (Transaminase >2 times the upper limit of normal)
- Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2)
- Uncontrolled thyroid disease (TSH undetectable or >10 mIU/L)
- A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
- Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's care companion
- Presence of a known adrenal disorder
- Active gastroparesis
- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
- Abuse of alcohol or recreational drugs
- Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis)
- Uncontrolled arterial hypertension (Resting diastolic blood pressure >90 mmHg and/or systolic blood pressure >160 mmHg)
- A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol
- Basal Rate <0.01 units/hour
- Inability to be physically active for more than 30 minutes per day
- Conditions that would make use of a CGM difficult (e.g., blindness, severe arthritis, immobility)
- Current enrollment in another intervention clinical trial
- List any restrictions on use of other drugs or treatments:
- Medications being taken to lower blood glucose, such as Pramlintide, Metformin, GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose
- Any other medication that the investigator believes is a contraindication to the subject's participation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
This is a single-center randomized crossover trial. The investigators will target completion of 15 adults (age 18-65 years) with Type 1 Diabetes who use an insulin pump. After completion of the Screening Visit, each subject will participate in a 28-day at home Data Collection Period while using their personal insulin pump, a personal glucometer, a study CGM, and a study activity tracker (i.e., Fitbit). This data collection period may be extended to obtain to gather more days of quality data, if needed per principal investigator judgement.
Once the data has been collected and processed, subjects will participate in two 24-hour admissions (Experimental and Control Admission) in a semi-controlled environment (i.e., hotel), performed in the assigned random order. During both admissions, subjects will use the personal insulin pump and glucometer, and a study CGM. The exercise session will consist of three 15-minute bouts of moderate-intensity exercise (i.e., stationary bicycle). Subjects will be provided a controlled dinner; the SI-informed bolus calculator will be used in the Experimental Admission while standard therapy will be used in the Control Admission. Subjects will then be observed overnight and discharged in the following morning.
Read the detailed description
Individuals with Type 1 Diabetes (T1D) require exogenous insulin to keep their blood glucose concentration in a safe euglycemic range, because of the absent internal insulin secretion caused by the autoimmune destruction of pancreatic beta-cells. As a consequence, the quality of glycemic control in T1D is heavily dependent on multiple daily treatment decisions by the patients, which are complicated by a wide variety of factors influencing insulin demand (e.g., circadian rhythms, physical activity, food, stress, etc.). Insulin sensitivity (SI) is a key metabolic parameter in diabetes as it informs on how sensitive the body is to the effects of insulin. In general, if someone has higher SI, the amount of insulin required to lower his blood glucose levels is smaller than that needed by someone who has low sensitivity. However, SI levels within the same person are not constant, and fluctuations of SI happen very frequently in the life of subjects with diabetes, making insulin dosing very difficult to tune.
In this context, the aim of this research project is to develop an SI-informed insulin bolus calculator, with the aim of tailoring the insulin dose to the individual's insulin need at the time the bolus is administered. The SI-informed bolus calculator relies on a Kalman filter-based algorithm which uses continuous glucose monitoring (CGM) data, insulin, and meal records to estimate SI. For each subject, a 24-hour SI profile is computed using data collected over several days of monitoring, and the optimal bolus is then computed by adjusting the standard insulin dose by the ratio between usual SI (from the profile) and real-time SI of the individual at the time the bolus is administered. In this way, if the real-time SI is larger/smaller than the profile SI at that time of day, the insulin dose will be reduced/incremented accordingly.
The study is thus designed as a single-center randomized clinical trial targeting completion of 15 subjects, who will undergo a 28-day at home Data Collection Period followed by two 24-hour admissions (Control and Experimental Admission) performed in random order in a semi-controlled environment (i.e., hotel). The Data Collection is meant to collect data needed to build the 24-hour SI profile for the subject. During the admissions, subjects will undergo a 45-minute afternoon exercise session designed to alter the late-afternoon/evening SI. The dinner meal will then be controlled, and the postprandial glycemic control obtained using the standard bolus calculator (Control Admission) will be compared to the control obtained in response to the optimized SI-informed bolus calculator (Experimental Admission). Metrics computed on CGM data will be compared between the two admissions, including mean blood glucose, time above 250 and 300 mg/dL, time below 70 and 54 mg/dL, and time in 70-180 mg/dL, the primary outcome being the postprandial exposure to hypoglycemia as measured by the Low Blood Glucose Index (a glycemic variability indicator which summarizes the number and extent of low blood glucose events in one single number). If successful, this study will provide a novel, data-oriented paradigm for insulin dosing in T1D.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- SI-Informed Bolus Calculator
- Keywords
- Continuous Glucose Monitor, Insulin Sensitivity, Exercise
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SI-Informed Bolus CalculatorOther
The SI-Informed Bolus Calculator will be used to dose the dinner meal insulin bolus during the Experimental Admission
| Study group | Role | What they receive |
|---|---|---|
| Experimental-Control | Other | Subjects randomized to this Arm would go through the Experimental Admission (SI-informed bolus calculator) first and Control Admission (regular bolus calculator) second Receives: Other: SI-Informed Bolus Calculator |
| Control-Experimental | Other | Subjects randomized to this Arm would go through the Control Admission (regular bolus calculator) first and Experimental Admission (SI-informed bolus calculator) second Receives: Other: SI-Informed Bolus Calculator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and feasibility of the SI-informed bolus calculator: Low Blood Glucose Index
Safety and feasibility of the SI-informed bolus calculator as measured by overall and postprandial occurrence of hypoglycemia quantified using the Low Blood Glucose Index (LBGI) computed from CGM data. LBGI is a previously introduced glucose variability measure and strong predictor of severe hypoglycemia, designed to aggregate the frequency and extent of low blood glucose events into a single number. By this definition, a higher LBGI may indicate a large number of mild hypoglycemic events, a small number of significant events, or a combination of both. As a higher LBGI indicates higher exposure to hypoglycemia, LBGI is expected to be better (i.e., lower) when the optimized bolus calculator is used, as compared to standard therapy.
Measured: LBGI will be assessed in the postprandial period following the controlled dinner meal (up to 4 hours following dinner) and overnight (e.g., from 11PM until 6AM), and will be compared between the two admissions.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2018
- Study start19 Nov 2018
- Primary completion31 Mar 2019
- Study completion31 Mar 2019
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 Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, DexCom, Inc.
- Responsible party
- Principal investigator, Chiara Fabris, PhD, University of Virginia
- Investigators
- Chiara Fabris, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03709108
- Sponsor's protocol ID
- 21040
- Status last verified
- Jul 2024
- First submitted
- 8 Oct 2018
- Last updated
- 17 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fabris C, Nass RM, Pinnata J, Carr KA, Koravi CLK, Barnett CL, Oliveri MC, Anderson SM, Chernavvsky DR, Breton MD. The Use of a Smart Bolus Calculator Informed by Real-time Insulin Sensitivity Assessments Reduces Postprandial Hypoglycemia Following an Aerobic Exercise Session in Individuals With Type 1 Diabetes. Diabetes Care. 2020 Apr;43(4):799-805. doi: 10.2337/dc19-1675. Epub 2020 Mar 6.
PubMed 32144167
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of an Insulin Sensitivity-Informed Bolus Calculator in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03709108
- Acronym / sponsor ID
- 21040
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Continuous Glucose Monitor, Insulin Sensitivity, Exercise
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, DexCom, Inc.
- Study start
- 19 Nov 2018 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 17 Oct 2018 (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.
This is a single-center randomized crossover trial. The investigators will target completion of 15 adults (age 18-65 years) with Type 1 Diabetes who use an insulin pump. After completion of the Screening Visit, each subject will participate in a 28-day at home Data Collection Period while using their personal insulin pump, a personal glucometer, a study CGM, and a study activity tracker (i.e., Fitbit). This data collection period may be extended to obtain to gather more days of quality data, if needed per principal investigator judgement.
Once the data has been collected and processed, subjects will participate in two 24-hour admissions (Experimental and Control Admission) in a semi-controlled environment (i.e., hotel), performed in the assigned random order. During both admissions, subjects will use the personal insulin pump and glucometer, and a study CGM. The exercise session will consist of three 15-minute bouts of moderate-intensity exercise (i.e., stationary bicycle). Subjects will be provided a controlled dinner; the SI-informed bolus calculator will be used in the Experimental Admission while standard therapy will be used in the Control Admission. Subjects will then be observed overnight and discharged in the following morning.
Detailed description
Individuals with Type 1 Diabetes (T1D) require exogenous insulin to keep their blood glucose concentration in a safe euglycemic range, because of the absent internal insulin secretion caused by the autoimmune destruction of pancreatic beta-cells. As a consequence, the quality of glycemic control in T1D is heavily dependent on multiple daily treatment decisions by the patients, which are complicated by a wide variety of factors influencing insulin demand (e.g., circadian rhythms, physical activity, food, stress, etc.). Insulin sensitivity (SI) is a key metabolic parameter in diabetes as it informs on how sensitive the body is to the effects of insulin. In general, if someone has higher SI, the amount of insulin required to lower his blood glucose levels is smaller than that needed by someone who has low sensitivity. However, SI levels within the same person are not constant, and fluctuations of SI happen very frequently in the life of subjects with diabetes, making insulin dosing very difficult to tune.
In this context, the aim of this research project is to develop an SI-informed insulin bolus calculator, with the aim of tailoring the insulin dose to the individual's insulin need at the time the bolus is administered. The SI-informed bolus calculator relies on a Kalman filter-based algorithm which uses continuous glucose monitoring (CGM) data, insulin, and meal records to estimate SI. For each subject, a 24-hour SI profile is computed using data collected over several days of monitoring, and the optimal bolus is then computed by adjusting the standard insulin dose by the ratio between usual SI (from the profile) and real-time SI of the individual at the time the bolus is administered. In this way, if the real-time SI is larger/smaller than the profile SI at that time of day, the insulin dose will be reduced/incremented accordingly.
The study is thus designed as a single-center randomized clinical trial targeting completion of 15 subjects, who will undergo a 28-day at home Data Collection Period followed by two 24-hour admissions (Control and Experimental Admission) performed in random order in a semi-controlled environment (i.e., hotel). The Data Collection is meant to collect data needed to build the 24-hour SI profile for the subject. During the admissions, subjects will undergo a 45-minute afternoon exercise session designed to alter the late-afternoon/evening SI. The dinner meal will then be controlled, and the postprandial glycemic control obtained using the standard bolus calculator (Control Admission) will be compared to the control obtained in response to the optimized SI-informed bolus calculator (Experimental Admission). Metrics computed on CGM data will be compared between the two admissions, including mean blood glucose, time above 250 and 300 mg/dL, time below 70 and 54 mg/dL, and time in 70-180 mg/dL, the primary outcome being the postprandial exposure to hypoglycemia as measured by the Low Blood Glucose Index (a glycemic variability indicator which summarizes the number and extent of low blood glucose events in one single number). If successful, this study will provide a novel, data-oriented paradigm for insulin dosing in T1D.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental-Control | Other | Other: SI-Informed Bolus CalculatorSubjects randomized to this Arm would go through the Experimental Admission (SI-informed bolus calculator) first and Control Admission (regular bolus calculator) second |
| Control-Experimental | Other | Other: SI-Informed Bolus CalculatorSubjects randomized to this Arm would go through the Control Admission (regular bolus calculator) first and Experimental Admission (SI-informed bolus calculator) second |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Type 1 diabetes for at least 12 months
- Current use of an insulin pump for at least 12 months
- Current or historical use of a CGM system for at least 6 months
- Age ≥18 to ≤65 years old
- HbA1c <8.5% at screening; if HbA1c <6.0% then total daily insulin must be ≥0.5 U/kg
Key exclusion criteria (27 listed)
- Diabetes ketoacidosis (DKA) in the 6 months prior to enrollment
- Clinically significant electrocardiogram (ECG) found at Screening as determined by the study medical physician
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment
- Currently being treated for a seizure disorder
- Coronary artery disease or heart failure, unless written clearance is received from a cardiologist or primary care provider and documentation of a negative stress test within the year
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 |
|---|---|---|
| SI-Informed Bolus CalculatorThe SI-Informed Bolus Calculator will be used to dose the dinner meal insulin bolus during the Experimental Admission | Other | Control-Experimental, Experimental-Control |
Primary outcome
Safety and feasibility of the SI-informed bolus calculator: Low Blood Glucose Index
Time frame: LBGI will be assessed in the postprandial period following the controlled dinner meal (up to 4 hours following dinner) and overnight (e.g., from 11PM until 6AM), and will be compared between the two admissions.
Safety and feasibility of the SI-informed bolus calculator as measured by overall and postprandial occurrence of hypoglycemia quantified using the Low Blood Glucose Index (LBGI) computed from CGM data. LBGI is a previously introduced glucose variability measure and strong predictor of severe hypoglycemia, designed to aggregate the frequency and extent of low blood glucose events into a single number. By this definition, a higher LBGI may indicate a large number of mild hypoglycemic events, a small number of significant events, or a combination of both. As a higher LBGI indicates higher exposure to hypoglycemia, LBGI is expected to be better (i.e., lower) when the optimized bolus calculator is used, as compared to standard therapy.
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 17 Jul 2024.
- Results publication: PubMed 32144167Fabris C, Nass RM, Pinnata J, Carr KA, Koravi CLK, Barnett CL, Oliveri MC, Anderson SM, Chernavvsky DR, Breton MD. The Use of a Smart Bolus Calculator Informed by Real-time Insulin Sensitivity Assessments Reduces Postprandial Hypoglycemia Following an Aerobic Exercise Session in Individuals With Type 1 Diabetes. Diabetes Care. 2020 Apr;43(4):799-805. doi: 10.2337/dc19-1675. Epub 2020 Mar 6.
- Individual participant dataSharing planned: No
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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.
Chiara Fabris, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SI-Informed Bolus Calculator in people with Type 1 Diabetes Mellitus, run by University of Virginia 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 9 inclusion and 27 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 17 Jul 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.
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?
Safety and feasibility of the SI-informed bolus calculator: Low Blood Glucose Index (time frame: LBGI will be assessed in the postprandial period following the controlled dinner meal (up to 4 hours following dinner) and overnight (e.g., from 11PM until 6AM), and will be compared between the two admissions.). 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 NCT03709108, 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 17 Jul 2024.