The aim of the study is to evaluate the efficacy of sensor augmented pump (SAP) therapy with MiniMed* 640G and SmartGuard* in preventing hypoglycemic events in comparison with continuous subcutaneous insulin infusion (CSII) therapy in type 1…
ID
Source
Brief title
Condition
- Diabetic complications
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Mean number of sensor glucose hypoglycaemic events below or equal to 55 mg/dL
(3.0 mmol/L) per patient/week. The mean number of sensor glucose hypoglycaemic
events will be calculated in each study arm and a between group comparison will
be performed. Sensor glucose data for the primary endpoint will consist of 6
weeks of sensor readings in both arms in the randomization phase (as
illustrated in Figure 1 (2 weeks (Visit 10 to 11) + 2 weeks (Visit 12 to 13) +
2 weeks (Visit 14 to 15)).
A hypoglycemic event is defined as sensor glucose values of 55 mg/dL (3.0
mmol/L) or less for more than 20 consecutive minutes. When the time between two
successive events is less than 30 minutes, they will be combined and counted as
one event.
Secondary outcome
Secondary endpoints:
* Mean number of sensor glucose hypoglycemic events * 40 mg/dL (2.2 mmol/L), *
55 mg/dL (3.0 mmol/L) and * 70 mg/dL (3.9mmol/L) and categorized by starting at
daytime (08:01 to 21:59) and night-time (22:00 to 08:00).
* Mean Time spent and AUC of sensor glucose values below or equal 40 mg/dL (2.2
mmol/L), 55 mg/dL (3.0mmol/L) and 70 mg/dL (3.9mmol/L) and categorized by
starting at daytime (08:01 to 21:59) and night-time (22:00 to 08:00).
* Mean Time spent and AUC of sensor glucose values above 180 mg/dL (10.0
mmol/L), 240 mg/dL (13.3 mmol/L), and 300 mg/dL (16.7 mmol/L) and categorized
by starting at daytime (08:01 to 21:59) and night-time (22:00 to 08:00).
* Mean Time spent of sensor glucose values within range and including 70-140
mg/dL (3.9 -7.8 mmol/L) and 70-180 mg/dL (3.9-10.0 mmol/L) and categorized by
starting at daytime (08:01 to 21:59) and night-time (22:00 to 08:00).
* Mean sensor glucose values surrounding SmartGuard triggered insulin
suspensions lasting <30, *30 to <90, and *90 to 120 minutes. Mean sensor
glucose values 60 min before and up to 360 min after suspend before low is
activated categorized by suspensions lasting less than 30, *30 to <90, *90 to
120 minutes, and categorized by starting at daytime (08:01 to 21:59) and
night-time (22:00 to 08:00).
* Proportion of Suspend before low events that reached the pre-set Low Limit
calculated, as per the individualised Low Limit settings at any given time
point.
* Excursion amplitudes of the glucose values measured by mean amplitude of
glycaemic excursions (MAGE), 24-hour standard deviation (SD) of glucose values.
* Mean HbA1c change from baseline to 6 months and stratified by baseline HbA1c
level *7.5% and
>7.5%.
Tertiary endpoints / descriptive analyses:
These will include and are not limited to the following (and also described in
the Statistical Analysis Plan):
* Safety endpoints: Number of severe hypoglycemic events, diabetic ketoacidosis
events, (Serious) Adverse Events, (Serious) Adverse Device Effects and Device
Deficiencies).
* Hypoglycemia-related number and mean duration of hospitalizations, number and
mean duration ICU (intensive care unit) care, number of emergency room
admissions, number of events requiring ambulance assistance and number of lost
days from school or work.
* Mean HbA1c level and mean number of sensor hypoglycemia events per week will
be reported by age group, duration of diabetes, duration of pump therapy at
time of screening, type of insulin analog used in study.
* Mean number of SMBG
* Mean Clarke, Gold, HFS and DTSQ questionnaire score.
* Mean weight and mean insulin total daily delivery dose.
Background summary
Managing type 1 diabetes requires constant vigilance and attention to diet,
exercise, and insulin regimens, and depends on consistently delivering the
right amount of insulin at the right time. Medtronic*s insulin delivery systems
have been helping type 1 diabetes patients with their diabetes management for
more than 30 years.
Hypoglycemia is an important barrier in achieving tight glycaemic control. Even
mild events of hypoglycemia have been shown to disrupt sleep, impair memory,
and cause inflammatory reactions, with impacts on driving, work and daily
living. Approximately one-third of patients with type 1 diabetes have evidence
of impaired hypoglycemia awareness, further increasing their risk of severe
hypoglycemia. However, avoidance of hypoglycemia in these patients has been
shown to restore awareness in small scale proof of concept studies. Till now,
most studies of CSII and CGM therapy have excluded these patients, and
therefore, there are few studies to demonstrate if these technologies can
provide an improvement specifically in this population.
The SMILE study will specifically recruit subjects with impaired awareness of
hypoglycaemia and aim to investigate if this technology can reduce the
incidence of hypoglycemia in this group of high risk patients.
Despite the available clinical evidence, as described above, SAP therapy is not
widely adopted, partly because CGM is not yet reimbursed in many countries. The
current clinical evidence on the ability of SAP to reduce the risk of
hypoglycemic events could be considered as not robust enough (e.g. short study
duration, small number of subjects, not the right comparator, sub-optimal
randomization process). Additional clinical evidence on the ability of SAP with
SmartGuard technology to reduce the risk of hypoglycemic events can potentially
lead to wider adoption and reimbursement of CGM technology to benefit patients*
needs.
In-clinic studies on MiniMed 640G with the Suspend before low feature of
SmartGuard demonstrated the safety and the efficacy of the investigational
configuration of this system after induced hypoglycemia. Additional clinical
evidence with the MiniMed 640G system and SmartGuard algorithm are required to
evaluate the efficacy in in-home settings for a longer duration and with more
'real life* variables inducing hypoglycemia, in comparison with CSII therapy,
as the current standard of care, to support SAP therapy adoption and CGM
reimbursement.
Study objective
The aim of the study is to evaluate the efficacy of sensor augmented pump (SAP)
therapy with MiniMed* 640G and SmartGuard* in preventing hypoglycemic events in
comparison with continuous subcutaneous insulin infusion (CSII) therapy in type
1 diabetes adults with an increased risk of hypoglycemia.
The primary study objective is to demonstrate a reduction in the mean number of
hypoglycemic events when using the MiniMed 640G system with the SmartGuard
algorithm:
The between group difference in the incidence of hypoglycemic events below or
equal 55 mg/dL (3.0 mmol/L) during 6 months of SAP therapy with SmartGuard, as
compared to patients on CSII therapy alone over the same period of time, in a
population of T1 diabetic patients with an increased risk of hypoglycemia, will
be evaluated. A reduction in the mean number of hypoglycemic events below the
threshold of 55 mg/dL (3.0 mmol/L) is estimated to be of clinical value.
The evaluation will be made by comparing subject sensor data collected in both
groups.
Secondary objectives will aim at evaluating the difference in glycemic
parameters and HbA1c.
Study design
A pre-market, multi-center, prospective, open label, adaptive, randomized
controlled study.
Intervention
Treatment:
All enrolled subjects will start a run-in phase, receive training and start
CSII therapy with the MiniMed 640G insulin pump and usage of blinded Continuous
Glucose Monitoring (CGM). Eligible subjects that meet the randomization
criteria assessed after the run-in phase will be randomized into the treatment
phase of 6 months:
* Treatment Arm: training and start of Sensor Augmented Pump therapy with
Suspend before Low feature of SmartGuard turned ON.
* Control Arm: continuation of CSII therapy alone with blinded CGM usage for a
total of 6 weeks during the treatment phase.
Randomization criteria:
If subjects meet the above criteria, as well as all of the following criteria
assessed at the end of the run-in period, they may continue to participate in
the treatment period of the study:
1. Subject has worn two weeks the sensor with transmitter during the run-in
period.
2. Subject has shown acceptable tolerance of Enlite 3 sensor wear, per
investigator judgment.
3. Subject performed * 4 finger stick blood glucose measurements daily, as
determined by CareLink Clinical data upload as the mean number of SMBG/day over
the past 14 days (SMBG number / day * 3.5 round up to 4).
4. Subject showed ability to comprehend the pump training and study procedures,
per investigator judgment.
Questionnaires: Clarke questionnaire, Gold questionnaire, Hypoglycemia Fear
Survey, Diabetes Treatment Satisfaction questionnaire at 3 visits within the
study period.
If no creatinine sample was taken within 3 months as of screening visit: 1
blood draw per patient is needed at screening to exclude patients from
participation that have signs of renal failure.
In tabel 5 op pagina 37 van het protocol staan de handelingen die op elke
visite worden gedaan beschreven.
Study burden and risks
Patients in this study all have Type 1 diabetes and are being treated with pump
therapy. There are risks associated to Type 1 diabetes independent from
participating in this study.
In this study the Enlite 3 glucose sensor and the GST3C transmitter will be
used. Both are not yet commercially available. Possible risks for the use of
the sensor are limited to reactions at the sensor insertion site, adhesives or
tape associated with sensor placement and irritation on the skin. (See protocol
page 62-64).
Currently these patients are being excluded for CSII and CGM therapy (SAP). In
this study patients with impaired awareness of hypoglycaemia can get access to
SAP treatment. Half of the study population will be treated with SAP. We expect
that the SAP with SmardGuard technology can reduce the incidence of
hypoglycemia in this group of high risk patients.The results of this
investigation can potentially lead to wider adoption and reimbursement of CGM
technology to benefit patients* needs.
Endepolsdomein 5
Maastricht 6229 GW
NL
Endepolsdomein 5
Maastricht 6229 GW
NL
Listed location countries
Age
Inclusion criteria
1. Age 24-75 years old at time of screening.
2. Diagnosed with Type 1 diabetes *10 years prior to screening.
3. On CSII therapy for * 6 months prior to screening.
4. Not on Real Time Continuous Glucose Monitoring for * 3 months prior to screening.
5. HbA1c value *5.8% and *10.0% as assessed by local lab * 15 days prior to screening or performed at screening.
6. A documented Severe Hypoglycemia event * 12 months prior to screening, OR Clarke score *4 assessed at time of screening, OR Gold score *4 assessed at time of screening.
7. Subject is willing to sign and date informed consent, comply with all study procedures and wear all study devices as required during the study.
Exclusion criteria
1. Untreated Addison*s disease, thyroid disorder, growth hormone deficiency, hypopituitarism or definite gastroparesis, per investigator judgment.
2. Subject is using Pramlintide (Symlin) SGLT2 inhibitor, GLP agonist at time of screening.
3. Renal failure defined by creatinine clearance <30 ml/min, as assessed by local lab test * 3 months before screening or performed at screening at local lab, as defined by the creatinine-based Cockcroft or MDRD equations.
4. Hearing or vision impairment hindering perception of glucose display and alarms, or otherwise incapable of using the study devices, per investigator judgment.
5. Current pregnancy or intention to conceive.
6. Any unresolved adverse skin condition in the area of sensor placement (e.g. psoriasis, rash, Staphylococcus infection).
7. Alcohol or drug abuse, other than nicotine, per investigator judgment.
8. Any other disease or condition that may preclude the patient from participating in the study, per investigator judgment.
9. Legally incompetent, illiterate or vulnerable person.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02733991 |
| CCMO | NL57532.028.16 |