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Diabetes Mellitus, Type 1DARENCT05669547

Dual Hormone Closed Loop in Type 1 Diabetes

A study testing dual hormone fully closed loop (DHFCL) in people with Diabetes Mellitus, Type 1 and Diabetes type1, run by UMC Utrecht at 14 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
dual hormone fully closed loop (DHFCL)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
243 participants
Where
14 sitesNetherlands
Study dates
3 Oct 2023to 15 Oct 2025
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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).

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Netherlands14 sites

  • Meander MC

    Amersfoort

  • Amsterdam UMC, AMC

    Amsterdam

  • Amsterdam UMC, VUmc

    Amsterdam

  • OLVG

    Amsterdam

  • Gelre Ziekenhuis

    Apeldoorn

  • Rijnstate

    Arnhem

  • Catharina Ziekenhuis

    Eindhoven

  • Martini Ziekenhuis

    Groningen

  • UMC Groningen

    Groningen

  • Tergooi Ziekenhuis

    Hilversum

  • LUMC

    Leiden

  • St. Antonius

    Nieuwegein

  • UMC Utrecht

    Utrecht

  • Isala Klinieken

    Zwolle

Other trials in Netherlands

About this study

Official title: Dual Hormone Closed Loop in Type 1 Diabetes: a Randomized Trial (DARE)

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.

Read the 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.

Being tested
dual hormone fully closed loop (DHFCL)
Keywords
dual hormone, fully closed loop, bihormonal pump, artificial pancreas
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dual hormone fully closed loop (DHFCL)Device

    Also called Inreda AP (Inreda Diabetic BV)

    dual hormone fully closed loop consisting of an algorithm, sensors and both insulin and glucagon infusion.

Study groups in NCT05669547
Study groupRoleWhat they receive
ControlNo interventionPatients currently on multiple daily injections (MDI) + continuous or flash glucose monitoring (CGM; FGM) or on a hybrid closed loop (HCL).
InterventionExperimentalPatients on dual hormone fully closed loop (DHFCL) therapy.
Receives: Device: dual hormone fully closed loop (DHFCL)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time in Range (TIR) at 12 months (measured with an independent FSL Pro IQ sensor)

    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.

    Measured: 12 months

Secondary outcomes (20)

  1. World Health Organization-Five Well-Being Index (WHO-5) score (Patient reported outcomes (PROMs)

    The World Health Organisation- Five Well-Being Index (WHO-5) is a short self-reported measure of current mental wellbeing.

    Measured: at 0, 3, 6, 9 and 12 months

  2. Health-related quality of life scores (EQ-5D-5L) (Patient reported outcomes (PROMs)

    As described on the Euroqol website, the EQ-5D-5L measures mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

    Measured: at 0, 3, 6, 9 and 12 months

  3. Problem Areas In Diabetes (PAID-5) score (Patient reported outcomes (PROMs)

    Evaluates problem areas in diabetes

    Measured: at 0, 3, 6, 9 and 12 months

  4. Diabetes Treatment and Satisfaction Questionnaire status and change (DTSQ-s and DTSQ-c) scores (Patient reported outcomes (PROMs)

    Measurement of treatment satisfaction

    Measured: at 0, 3, 6, 9 and 12 months

  5. Hypoglycaemia Fear Survey-II (HFS-II) Worry subscale score; (Patient reported outcomes (PROMs)

    Measures hypoglycaemia fear

    Measured: at 0, 3, 6, 9 and 12 months

  6. Pittsburgh Sleep Quality Index score (Patient reported outcomes (PROMs)

    Measures sleep quality and duration

    Measured: at 0, 3, 6, 9 and 12 months

  7. Insulin delivery systems: perceptions, ideas, reflections and expectations (INSPIRE) scores (Patient reported outcomes (PROMs)

    Measures ideas, perceptions and expectations of the insulin device - only for HCL (control) and DHFCL groups

    Measured: at 0, 3, 6, 9 and 12 months

  8. Hypoglycaemia unawareness (Gold-Clarke) (Patient reported outcomes (PROMs)

    Measurement of hypoglycaemia unawareness

    Measured: at 0 and 12 months

  9. Cost-effectiveness: cost per quality adjusted life year.

    To determine the cost-effectiveness of treatment with the DHFCL. Including data:

    Medical Consumption Questionnaire (MCQ), at 0, 3, 6, 9 and 12 months; Productivity Cost Questionnaire (PCQ), at 0, 3, 6, 9 and 12 months; Detailed hospital health care consumption for each individual patient (collected from electronic patient files, including unplanned contact moments) Cost effectiveness: cost per quality adjusted life year.

    Measured: 12 months

  10. Other glycaemic outcomes

    Including Time Below Range (TBR), Time Above Range (TAR), glycaemic variability, number of hypoglycemic events and HbA1c.

    Measured: at 0, 3, 6, 9 and 12 months

  11. Time Above Range (TAR) Other glycaemic outcomes

    Measured with an independent Freestyle Libre Pro IQ sensor

    • level 1 and 2 hyperglycaemia: >10.0 mmol/l;
    • level 2 hyperglycaemia: >13.9 mmol/l;

    Measured: at 0, 3, 6, 9 and 12 months

  12. Time Below Range (TBR) Other glycaemic outcomes

    Measured with an independent Freestyle Libre Pro IQ sensor

    • level 1 and 2 hypoglycaemia: <3.9 mmol/l;
    • level 2 hypoglycaemia: <3.0 mmol/l;

    Measured: at 0, 3, 6, 9 and 12 months

  13. Number of hypoglycaemic events Other glycaemic outcomes

    Measured with an independent Freestyle Libre Pro IQ sensor defined as glucose <3.0 mmol/l for 15 consecutive minutes when the time between two successive events is less than 30 minutes, they will be combined and counted as one event

    Measured: at 0, 3, 6, 9 and 12 months

  14. Mean glucose Other glycaemic outcomes

    Measured with an independent Freestyle Libre Pro IQ sensor

    • day and night;
    • day: from 06:00 to 23:59 hours;
    • night: from 00:00 to 05:59 hours;

    Measured: at 0, 3, 6, 9 and 12 months

  15. Glycaemic variability Other glycaemic outcomes

    Based on independent Freestyle Libre Pro IQ sensor data

    • Coefficient of variation;
    • Standard deviation.

    Measured: at 0, 3, 6, 9 and 12 months

  16. HbA1c Other glycaemic outcomes

    venipuncture

    • Mean;
    • Percentage patients achieving HbA1c ≤ 53 mmol/mol.

    Measured: at 0, 3, 6, 9 and 12 months

  17. Long-term safety outcomes

    To assess long-term safety of the DHFCL, including the incidence of (severe) adverse events, incidence of device issues and the effects of excluding daily use of acetaminophen on non steroidal inflammatory drug (NSAIDs) use and associated drug complications rate.

    Measured: 12 months

  18. Daily insulin use (units/day) DHFCL outcomes

    Measured by DHFCL device

    Measured: at 3, 6, 9 and 12 months

  19. daily glucagon use.DHFCL outcomes

    Measured by DHFCL device Daily insulin use, daily glucagon use and percentage of time glucose control algorithm active at 0, 3, 6, 9 and 12 months.

    Measured: at 3, 6, 9 and 12 months

  20. Percentage of time glucose control algorithm active DHFCL outcomes

    Measured by DHFCL device

    Measured: at 3, 6, 9 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2023
  2. Study start3 Oct 2023
  3. Primary completion15 Oct 2025
  4. Study completion15 Oct 2025

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
243 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05669547
Sponsor's protocol ID
22/671
Acronym
DARE
Status last verified
Jan 2026
First submitted
22 Nov 2022
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jancev M, Snoek FJ, Frederix GWJ, Knottnerus H, Blauw H, Witkop M, Moons KGM, van Bon AC, DeVries JH, Serne EH, van Sloten TT, de Valk HW; DARE study consortium. Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands - study protocol. BMJ Open. 2023 Aug 23;13(8):e074984. doi: 10.1136/bmjopen-2023-074984.

    PubMed 37612114

Questions about this trial

What is this clinical trial studying?

A study testing dual hormone fully closed loop (DHFCL) in people with Diabetes Mellitus, Type 1 and Diabetes type1, run by UMC Utrecht at 14 sites in Netherlands.

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 13 inclusion and 13 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 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Netherlands. 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?

Time in Range (TIR) at 12 months (measured with an independent FSL Pro IQ sensor) (time frame: 12 months). 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 NCT05669547, 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 21 Jan 2026.

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