Clinical trial NCT05669547: Dual Hormone Closed Loop in Type 1 Diabetes
Official title: Dual Hormone Closed Loop in Type 1 Diabetes: a Randomized Trial (DARE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Diabetes type1
Diabetes
Keywords: dual hormone
fully closed loop
bihormonal pump
artificial pancreas
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Dutch National Health Care Institute
name: Inreda Diabetic B.V.
First posted: 2023-01-03
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a 12 month open-label, two-arm randomised parallel-group trial in adult type 1 diabetes patients executed in 14 centres in the Netherlands. The aim of this study is to determine the long-term clinical effectiveness of treatment with a dual-hormone (insulin and glucagon) fully closed loop system during 12 months compared to the current most used care and to the currently most advanced technological care. Secondary objectives include the assessment of cost-effectiveness, Patient Reported Outcome Measures (PROMs), other glycaemic outcomes and safety.

Detailed description: Rationale: Patients with type 1 diabetes mellitus (T1DM) require lifelong insulin therapy. Insulin therapy improves but does not fully normalise blood glucose levels with current therapies. Current therapies include subcutaneous insulin injection or subcutaneous insulin infusion, combined with a device to measure glucose levels (finger stick, intermittent sensor or continuous glucose monitoring). Although having provided a huge improvement in glycaemic control, patients have to work hard every day and still have to calculate mealtime boluses. An automated insulin delivery device covering both basal and prandial insulin requirement would mean another great leap forwards. The dual-hormone fully closed loop (DHFCL) provides such a new strategy of automated insulin delivery coupled with targeted glucagon infusion as insulin-antagonist to even more approximate normal physiology.

Objective: To determine the long-term clinical effectiveness of treatment with a dual-hormone (insulin and glucagon) fully closed loop system during 12 months compared to the current most used care and to the currently most advanced technological care. Secondary objectives include the assessment of cost-effectiveness, Patient Reported Outcome Measures (PROMs), other glycaemic outcomes and safety.

Study design: A 12 month open-label, two-arm randomised parallel-group trial. Study population: Adult (age ≥18 years) patients with T1DM for at least 1 year with an HbA1c at entry ≤ 91 mmol/mol.

Intervention: The study includes two separately randomised arms, defined by current diabetes treatment. In one arm, patients currently on Multiple Daily Injections (MDI; at least once daily long-acting insulin and thrice daily short-acting insulin) in combination with continuous or flash glucose monitoring (CGM or FGM; currently the most used strategy) are 1:1 randomised to either the intervention, i.e. the DHFCL, or continuation of their current treatment. In the other arm, patients currently on hybrid closed loop treatment (HCL; presently the most advanced diabetes control treatment) are 1:1 randomised to either the intervention or continuation of their current care.

Main study parameters/endpoints: The main study endpoint is the Time in Range (TIR; % of time spent in the 3.9-10 mmol/l target range) at 12 months, which will be compared between the intervention and the control treatment within each arm. Secondary endpoints include cost-effectiveness, PROMs, other glycaemic outcomes, safety measures and device-related outcomes.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 75 years;
* Diagnosed with type 1 diabetes mellitus at least one year ago;
* HbA1c ≤ 91 mmol/mol;
* Treated with either MDI with FGM/CGM or treated with HCL:

  * MDI+FGM/CGM for ≥ 3 months with an adequate sensor use during at least 70% of the time in the month prior to screening (based on sensor usage from the download summary report of the FGM/CGM);
  * HCL for ≥ 3 months with a frequency of use ≥ 70% of the time in auto mode over the previous month prior to screening;
* Does not reach the treatment goals over the last 8 weeks:

  * for MDI+FGM/CGM: subject has a TIR \<80% or Time Below Range (TBR) \>4%;
  * for HCL: subject has a TIR \<80% or TBR \>4%;
* Willing to take or switch to insulin Humalog when randomized to the intervention DHFCL arm;
* Under treatment in one of the participating centres;
* Willing and able to sign informed consent;
* Access to internet at home (for DHFCL data upload).

Exclusion Criteria:

* Current use of non-approved HCL device;
* BMI \>35 kg/m2;
* eGFR\<30 mL/min/1.73m2;
* Plan to change usual diabetes regimen in the next 3 months;
* Current participation in another diabetes-related clinical trial;
* Actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or device in the last 2 weeks before enrolment into this study, as per investigator judgment;
* Established history of allergy or severe reaction to adhesive or tape that must be used in the study;
* Use of oral glucose-lowering medication;
* Active retinopathy or painful neuropathy;
* Daily use of acetaminophen during the trial (all arms), as this may influence the sensor glucose measurements. Incidental use with a maximum of e.g. 3 daily doses of 1000mg paracetamol for a maximum of 3 consecutive days is allowed
* Limited ability to see, and to hear or feel alarm signals of the closed loop system;
* Current pregnancy, breast feeding or planning to become pregnant in the 12 months of the trial or using ineffective birth control methods;
* Presence of a medical or psychiatric condition, longstanding serious adherence problems, anticipated problems in handing over diabetes control to a device or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant.

Primary outcomes:
measure: Time in Range (TIR) at 12 months (measured with an independent FSL Pro IQ sensor)
timeFrame: 12 months
Secondary outcomes:
measure: World Health Organization-Five Well-Being Index (WHO-5) score (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Health-related quality of life scores (EQ-5D-5L) (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Problem Areas In Diabetes (PAID-5) score (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Diabetes Treatment and Satisfaction Questionnaire status and change (DTSQ-s and DTSQ-c) scores (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Hypoglycaemia Fear Survey-II (HFS-II) Worry subscale score; (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Pittsburgh Sleep Quality Index score (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Insulin delivery systems: perceptions, ideas, reflections and expectations (INSPIRE) scores (Patient reported outcomes (PROMs)
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Hypoglycaemia unawareness (Gold-Clarke) (Patient reported outcomes (PROMs)
timeFrame: at 0 and 12 months
measure: Cost-effectiveness: cost per quality adjusted life year.
timeFrame: 12 months
measure: Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Time Above Range (TAR) Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Time Below Range (TBR) Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Number of hypoglycaemic events Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Mean glucose Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Glycaemic variability Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: HbA1c Other glycaemic outcomes
timeFrame: at 0, 3, 6, 9 and 12 months
measure: Long-term safety outcomes
timeFrame: 12 months
measure: Daily insulin use (units/day) DHFCL outcomes
timeFrame: at 3, 6, 9 and 12 months
measure: daily glucagon use.DHFCL outcomes
timeFrame: at 3, 6, 9 and 12 months
measure: Percentage of time glucose control algorithm active DHFCL outcomes
timeFrame: at 3, 6, 9 and 12 months
Other outcomes:
measure: Patient reported daily insulin use control group
timeFrame: at 3, 6, 9 and 12 months
measure: Weight (kg) at baseline and 12 months
timeFrame: 12 months
measure: Blood pressure (SBP/DBP in mmHg) at baseline and 12 months
timeFrame: 12 months
measure: Heart rate (/min) at baseline and 12 months
timeFrame: 12 months
measure: Frequency of unplanned patient contact with the diabetes team
timeFrame: at 3, 6, 9 and 12 months
measure: Concomitant medication, at screening, baseline, 3, 6, 9 and 12 months
timeFrame: at screening, baseline, 3, 6, 9 and 12 months
measure: Continuation rate of the DHFCL
timeFrame: at 12 months
measure: Reasons for discontinuation of the DHFCL treatment.
timeFrame: at 3, 6, 9 and 12 months
Locations:
city: Amersfoort
country: Netherlands
facility: Meander MC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, VUmc
city: Amsterdam
country: Netherlands
facility: OLVG
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuis
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Hilversum
country: Netherlands
facility: Tergooi Ziekenhuis
city: Leiden
country: Netherlands
facility: LUMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
References: