Managing insulin dosing for diabetes, particularly for those with type 1 diabetesmellitus, is a complex process that requires precision. Insulin bolus calculators aredesigned to help patients calculate their insulin needs based on variables such ascarbohydrate intake, blood glucose levels, and insulin sensitivity. However, to ensurethese tools are safe and effective, clinical trials are essential. The primary purpose ofthis trial is to assess the safety and efficacy of the bolus calculator - Diabetes M inproviding accurate insulin dosing and preventing the risk of hypoglycemia andhyperglycemia, which can lead to severe complications. The clinical trial is critical toensure patient's safety and build confidence in the use of the bolus insulin calculatorin real-world settings. Insulin dosing errors, whether too high or too low, can lead toserious health risks, including hypoglycemia, hyperglycemia, and long-term diabetescomplications. By conducting a controlled study, the trial will evaluate how well thebolus calculator performs in preventing these risks, comparing its recommendations tostandard practices. This will help determine whether the calculator can consistentlyimprove blood glucose management while minimizing human error in insulin dosingdecisions. Finally, regulatory approval from bodies like the Food and Drug Administration(FDA) requires clear evidence of safety and efficacy. The data from this clinical trialwill not only support regulatory submissions but also demonstrate the bolus calculator'sclinical utility in improving outcomes like glycemic control and patient compliance. Byempowering patients to make more informed dosing decisions and reducing the complexity ofdiabetes management, this trial could pave the way for broader adoption of thistechnology and ultimately improve the quality of life for patients with type 1 diabetesmellitus.
The primary objective of this study is to compare the effect of Diabetes M application
use versus conventional bolus calculation (bolus wizard calculation in continuous
subcutateous insulin infusion (CSII) or determined insulin:carb ratio (ICR) calculation
in multiple daily injections regimen (MDI)) on glycaemic control, measured by time in
range (TIR) in percentage defined as time spent in blood glucose levels between 3.9-10.0
mmol/l, in patients with type 1 diabetes on MDI or CSII.
The secondary objectives of this study are: 1) to compare the risk of hypoglycaemic
episodes or time below range or time above range (TBR) in percentage, defined as time
spent in blood glucose levels between 3.5-3.9 mmol/l level 1 and < 3.5 mmol/l level 2, in
patients with type 1 diabetes on MDI or CSII using Diabetes M application versus
conventional bolus calculation (bolus wizard calculation in CSII or determined ICR
calculation in MDI); 2) to compare the risk of hyperglycaemic episodes or time above
range (TAR) in percentage, defined as time spent in blood glucose levels between
10.0-13.0 mmol/l high and >13.0 mmol/l very high, in patients with type 1 diabetes on MDI
or CSII using Diabetes M application versus conventional bolus calculation (bolus wizard
calculation in CSII or determined ICR calculation in MDI); and 3) to compare time in
tight range (TITR) in percentage, defined as time spent in blood glucose levels between
3.9-7.8 mmol/l in patients with type 1 diabetes on MDI or CSII using Diabetes M
application versus conventional bolus calculation (bolus wizard calculation in CSII or
determined ICR calculation in MDI).
Trial design This is a 4-week, open-label, non-randomized, single-armed, one-centre,
proof of concept clinical trial. All subjects enrolled in the trial will be followed-up
for 2-weeks on their usual treatment and then Diabetes M app will be applied. There is a
2-week screening period followed by enrolment visit (V1). At V1 venuos blood samples will
be taken for laboratory tests all participants from all participants. Then there is a
2-week follow-up period on usual treatment ending with visit 2 (V2) when CGM data for the
period will be downloaded and Diabetes M application will be installed. All individual
parameters for the participants will be filled in the application and the participants
will be instructed in details on how to use the application. Then there is a 2-week
treatment period using Diabetes M application ending with visit 3 (V3) when CGM data for
the period will be downloaded. Total trial duration for the individual subject will be
approximately 6 weeks. The trial population will consist of subjects with type 1 diabetes
treating with MDI or CSII and using continuous glucose monitoring (CGM).
Subject and trial completion Approximately 40 subjects will be screened in order to
achieve 30 subjects to be assigned. The number of subjects expected to complete the trial
will be 27 subjects (calculated 10% drop-off). Subjects will be followed for the planned
duration of the trial.
Trial period completion for a subject is defined as when the enrolled subject has
completed the final scheduled visit 'end of trial', visit 3. Date of trial completion is
the date the subject completed the final scheduled visit, as mentioned above.
Treatment period completion for a subject is defined as when the subject has received the
required treatment and attended the end of treatment visit 3.
Scientific rationale for trial design The treatment duration of the trial is 4 weeks,
including 2 weeks on conventional bolus calculation and 2 weeks on Diabetes M app. A
2-week treatment duration is comparable to trials conducted with a previously approved
device, which will serve as a predicator in the current study, and will provide robust
data for the evaluation of efficacy and safety parameters. This open-label,
non-randomized, single-armed, one-centre, proof of concept clinical trial design has the
poor to accurately assess the effect and safety of Diabetes M application as an
alternative bolus calculator in subjects with type 1 diabetes on MDI or CSII. The trial
includes a screening visit to assess the subject's eligibility. After enrollment visit,
there are 2 visits scheduled. Visit 2 is scheduled 2 weeks after enrolment for switching
from conventional treatment to Diabetes M app installation and use. An end of trial visit
3 for efficacy and safety assessments is scheduled 2 weeks after visit 2.
The trial population will consist of subjects with type 1 diabetes on treatment with MDI
or CSII using CGM. Patients with type 1 diabetes represent a clinically relevant
high-risk population and it is highly likely to benefit from the use of such an
application.
Prospective approval of protocol deviations to recruitment and enrolment criteria, also
known as protocol waivers or exemptions, is not permitted.
Full guide for using the Diabetes:M mobile app, can be accessed at
- In English https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/en/topic/introduction
- In Bulgarian https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/bg/topic/introduction Auxiliary supplies
The following auxiliary supplies will be provided by investigators:
- Glucometer and blood strips for calibration if needed
- Three refills of CGM sensors Dexcom One plus (each lasts 10 days for a total of 30
days or 4 weeks). The study requires that participants use the standard Dexcom
mobile app and that the Primary Investigator can download their daily data from the
physician online access provided by Dexcom.
Only supplies provided by investigators must be used for the administration of the trial
product.
Device: Diabetes M bolus calculator
Diabetes:M Bolus Calculator is an application for precise bolus insulin dose. Full guide
for using the Diabetes:M mobile app, can be accessed at
- In English https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/en/topic/introduction
- In Bulgarian https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/bg/topic/introduction Instructions for the subject Trial participants
must use the Diabetes:M Bolus Calculator before every insulin application and must
record the insulin units applied.
Step-by-step instructions for bolus calculation via Diabetes:M app:
1. Open Diabetes:M app
2. Go to Bolus Advisor
3. Enter blood sugar, carbohydrates
4. Tap Calculate
5. Tap Save button
6. Confirm transferring the bolus to log entry screen
7. Enter note and some feedback if needed
8. Tap Save button to save the record
Device: Diabetes M app
Diabetes:M Bolus Calculator is an application for precise bolus insulin dose. Full guide
for using the Diabetes:M mobile app, can be accessed at
- In English https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/en/topic/introduction
- In Bulgarian https://www.manula.com/manuals/sirma-medical-systems/diabetes-m-user-
guide/mobile/bg/topic/introduction Instructions for the subject Trial participants
must use the Diabetes:M Bolus Calculator before every insulin application and must
record the insulin units applied.
Step-by-step instructions for bolus calculation via Diabetes:M app:
1. Open Diabetes:M app
2. Go to Bolus Advisor
3. Enter blood sugar, carbohydrates
4. Tap Calculate
5. Tap Save button
6. Confirm transferring the bolus to log entry screen
7. Enter note and some feedback if needed
8. Tap Save button to save the record
Inclusion Criteria:
- Subjects are eligible to be included in the trial only if all the following criteria
apply:
1. Informed consent obtained before any trial-related activities. Trial-related
activities are any procedures that are carried out as part of the trial,
including activities to determine suitability for the trial.
2. Ability to adhere to the study visit schedule and other protocol requirements.
3. Male or female, age from 18 years to 75 years at the time of signing informed
consent.
4. Diagnosed with type 1 diabetes regardless of the disease duration.
5. On treatment with MDI or CSII.
6. Using CGM.
7. eGFR-EPI ≥ 45 ml/min/1.73m 2 .
Exclusion Criteria:
- Subjects are excluded from the trial if any of the following criteria apply:
Diabetes related
1. Male or female, age < 18 years or > 75 years. 2. Diagnosed with type 2
diabetes. 3. Diagnosed with diabetes proliferative retinopathy. 4. Renal impairment
measured as estimated glomerular filtration rate (eGFR-EPI) value of < 45
mL/min/1.73 m 2 according to KDIGO. 5. Frequent severe hypoglycaemic episodes
(<3.5 mmol/l). 6. Any acute illnesses, which might influence glycaemic control in
short term. General safety 8. Myocardial infarction, stroke, hospitalization for
unstable angina pectoris or transient ischaemic attack within 3 months prior to the
day of screening. 9. Presently classified as being in New York Heart Association
(NYHA) Class IV. 10. Presence or history of malignant neoplasm within 5 years prior
to the day of screening.
11. Female who is pregnant, breast-feeding or intends to become pregnant or is of
child-bearing potential and not using a highly effective contraceptive method. 12.
Any disorder, unwillingness or inability, which in the investigator's opinion, might
jeopardise the subject's safety or compliance with the protocol.
University Hospital for Active Treatmnet in Endocrinology "Acad Ivan Penchev" EAD, Medical University of Sofia
Sofia, Bulgaria
Not Provided