Assess the Impact of Insulclock on Glycemic Variability and Treatment Compliance in Uncontrolled DM1 Patients
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      Insulclock® is a small electronic device developed to facilitate the optimal administration
      of insulin. This device works as an add-on module of commercially available insulin pens and
      monitors the date, time and dose of injections, the type of insulin injected, the duration of
      injections and insulin temperature. The Insulclock 360 app allows automatic data logging,
      report generation and reminder setting, among other functions. In this study, we pretend to
      show the clinical impact of Insulclock system, both device and mobile application, on
      glycemic indices, treatment compliance, and quality of life in patients with persistent
      poorly controlled T1DM.

      Material and methods: Randomized open-label multicenter controlled trial to evaluate glycemic
      control, the number of missed and delayed insulin doses, and quality of life after seven
      weeks of Insulclock 360 use in participants with uncontrolled DM1. We will also compare these
      results between patients with or without receiving system reminders and alerts.

      This study aims to assess the effect of Insulclock on glycemic control, treatment adherence,
      and quality of life. As a secondary objective, we will compare the study outcomes between
      participants in the Active and Masked Insulclock groups (i.e., with or without receiving
      alerts and reminders and accessing the app).

      To assess glycemic control, we will measure HbA1C and glycemic indices. Glycemic variability
      indices will be monitored with the FreeStyle Libre™ and included glucose coefficient of
      variation (CV), standard deviation (SD), time in range (TIR), time above range (TAR), and
      time below range (TBR). Mean glucose levels will be obtained from 48-h time intervals with
      the FreeStyle Libre.

      A late meal bolus (mistimed) will be considered when Insulclock detects the injection at
      least 30 minutes after the CGM rise. To identify meal glucose excursions, we will use the
      Glucose Rate Increase Detector (GRID) algorithm, which estimates the rate of change (ROC) of
      glucose from CGM data.

      Participants will complete the ITSQ and the DTSQ, which are validated questionnaires to
      assess the diabetes treatment satisfaction.
    

Detailed description: 
      Study design:

      This multicentric randomized open-label study will be conducted at the Hospital General de
      Segovia (Segovia, Spain), Hospital de Cruces (Bilbao, Spain), Hospital Arquitecto Marcide
      (Ferrol, A Coruña, Spain) and Hospital Central de Asturias (Oviedo, Spain) after
      classification by the Spanish Agency for Medicines and Health Products (AEMPS) and ethical
      approval by the Ethics Review Committee of each research center. The study will be conducted
      in compliance with the ethical principles of the Declaration of Helsinki. Each participant
      will provide written informed consent before being included in the study.

      The study is scheduled across seven visits. At Visit 1 (Screening, Week -1), demographic and
      clinical information will be collected, and concomitant medications will be registered. All
      potential study patients will be screened for eligibility after signing the informed consent
      form (ICF) and will be assigned with a patient identification number. Laboratory evaluations
      (HbA1c, serum chemistry) must be available within the last 2 months. An identification number
      will be assigned to each participant At Visit 2 (Run-in, week 0), participants will receive
      information on the use of the Insulclock device and app on masked mode (excluding the use of
      Insulclock 360 app information and alarms). If the participant does not use a CGM: a
      healthcare professional applies the FreeStyle Libre sensor to the back of the upper arm and
      activates it. If the participant already uses a CGM system, the patient will be encouraged to
      use sensors during this period.

      At Visit 3 (First Visit CGM 1, week 1) and Visit 4 (Follow-up, week 3), participants will be
      encouraged to use the system At Visit 5 (Visit Starting CGM 2 and Randomization, week 4)
      participants will be randomized (1:1) to the Active Insulclock group or the Masked Insulclock
      group. Participants randomized in the Insulclock Active Group will receive detailed
      instructions on using the Insulclock device and Insulclock 360 mobile application and will be
      instructed and motivated for full use of all system functions (alarms, messages to the
      caregivers and investigation team). Participants randomized in the Insulclock Masked Group
      will be instructed on the correct installation and use of the Insulclock system for recording
      insulin bolus information but they will not receive any other information and will not have
      access to the Insulclock 360 application from the Internet and will keep administering
      insulin treatment as before. A healthcare professional will apply a FreeStyle Libre sensor to
      the upper arm in all the participants who do not use a CGM and will be encouraged to wear the
      sensor for 2 weeks. Participants who already use a CGM system will be encouraged to use
      sensors during this period.

      At Visit 6 (Final Visit CGM 2 and Randomization, week 6). Participants will receive a
      reminder on the use of Insulclock according to the corresponding group.

      At Visit 7 (Final Visit, week 7) the mobile application diaries will be collected and
      reviewed. Participants will receive to fill in the Insulin Treatment Satisfaction
      Questionnaire (ITSQ) and the Diabetes Treatment Questionnaire (DTSQ).

      Study population Investigators will include 80 participants aged 18-80 years with
      uncontrolled T1DM who provide written informed consent. Persistent uncontrolled T1DM was
      defined as HbA1C levels ≥6.5% for at least 1 year, and/or variations ≥1% in HbA1C within the
      previous 2 years and attending regular (more than 2 per year) follow-up visits at the
      Endocrinology department. Investigators will exclude pregnant or breastfeeding women,
      individuals with a history of or current alcohol or drug abuse, acute infection, cognitive
      decline or dementia, or any illness or condition that could interfere with the trial.

      Study devices:

      Insulclock is a small electronic device that works as an add-on module of insulin pens. This
      device can record the dose and time of insulin injected, register temperature changes of
      insulin pens, record the duration of an injection, and the specific insulin pen used. In the
      present study, participants self-administer insulin with pens coupled to Insulclock and
      according to routine clinical practice. By means of acoustic and visual alarms, participants
      receive information for a correct injection technique (an alert if the injection time was <6
      seconds) or to prevent stacking insulin (an alert if a previous injection was done within the
      2 previous hours).

      The Insulclock device is synchronized with the Insulclock 360 app for the automatic logging
      of patient data. The Insulclock 360 app also has a reminder function to promote the timely
      administration of insulin doses. Users can also receive customized tips on DM management with
      the "my tutors" tool and obtain information on DM topics. Insulclock 360 app is compatible
      with Apple and Android operating systems.

      In the Active group, participants will receive acoustic and visual alarms, device-related
      information and will have access to the Insulclock 360 app. In the Masked group, participants
      know the dose, time and duration of injections, but these participants will not receive any
      reminder and will be masked to the Insulclock 360 app.

      Participants will use the Freestyle Libre (Abbott Diabetes Care, Witney, Oxon, UK) for the
      continuous monitoring of glucose levels. This flash continuous monitoring system is to be
      worn on the upper arm and does not require capillary glucose concentrations for calibration.
      The sensor automatically records glucose data every 15 minutes for 14 days.

      Statistical Analysis The proposed statistical analysis methods constitute a synthesis of the
      methods to be used in this study to apply them to the data collected and respond to the
      general objective and the specific objectives.

      Data from all participants included in the study, who meet the selection criteria, will be
      analyzed. Data in absentia will not be charged and will be considered as lost.

      A general description of the variables included in the study will be made. The absolute and
      relative frequency distributions of the qualitative variables will be presented by
      investigators, as well as the measures of central tendency and dispersion (mean, standard
      deviation, median, minimum and maximum) of the quantitative variables. The confidence
      intervals will be presented at 95% for the main quantitative outcome variables associated
      with the main objective and the main secondary variables.

      The data corresponding to the variables included in the main objective will be descriptively
      analyzed.

      Investigators will use the SPSS software Version 17.0. to perform the analysis. The
      hypothesis tests that are carried out will be in all bilateral cases and with a significance
      level of 0.05. For variables that do not fit the normal distribution(or parametric), the Mann
      Whitney hypothesis tests will be used (for unpaired data). The chi-square test (or Fischer's
      exact test when appropriate) will be used for the analysis of contingency tables as well as
      for the comparison of proportions and/or frequency distributions.
    

Intervention name(s): Use of Insulclock system, both Insulclock device and Insulclock 360 app.; Use of Insulclock system, both Insulclock device and Insulclock app on masked mode.
Intervention type(s): Device; Device
Intervention description(s): Visit 5, during week 4.
Randomization will be applied:
Active group will use all functionalities of Insulclock 360. They will have reminders, all their information and statistics at the disposition of the patient and healthcare providers, they have the assistance if desired of an ally or caregiver, a bolus calculator and the rest of functionalities described in the protocol.; Visit 5, during week 4.
Randomization will be applied:
Masked group will remain with the masked system, without functionalities.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: All participants will start the study using Insulclock, device and app on Masked Mode. At the week 4 patients will be randomized (1:1) to the Active Insulclock group or the Masked Insulclock group. Patients randomized in the Insulclock Active Group will receive detailed instructions on using the Insulclock device and Insulclock 360 mobile application and will be instructed and motivated for full use of all system functions (alarms, messages to the caregivers and investigation team). Patients randomized in the Insulclock Masked Group will be instructed on the correct installation and use of the Insulclock system for recording insulin bolus information but they will not receive any other information and will not have access to the Insulclock 360 application from the Internet and will keep administering insulin treatment as before. A healthcare professional will apply a FreeStyle Libre sensor to the upper arm in all the participants who do not use a CGM.
Masking: Single (Participant)
Primary purpose: Supportive Care
Keywords: Type 1 Diabetes Mellitus; Insulin Pen; Glycosylated Hemoglobin; Time in Range; Adherence; Continuous Glucose Monitoring; Insulclock; Basal glycaemia; Preprandial glycaemia; Endocrine System Diseases; Insulin-dependent; Glucose Metabolism Disorders