Type 1 DiabetesPhase 4DHCL2021NCT04949867
Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes
A Phase 4 study testing Glucagon and Closed-loop System in people with Type 1 Diabetes, run by Steno Diabetes Center Copenhagen at 2 sites in Denmark.
Trial summary
Objective: To assess the efficacy and safety of an insulin-glucagon dual-hormone (DH) closed-loop system compared with an insulin-only single-hormone (SH) closed-loop system in adolescent with type 1 diabetes. Read more about this study
- Who is it for?
- Ages 13 to 17 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Glucagon and Closed-loop System
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 2 sitesDenmark
- Study dates
- 20 May 2021to 26 Apr 2022
- Phase
- Phase 4
- 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 13 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age = 13-17 years
- T1D duration ≥ 2 years
- Insulin pump therapy ≥ 1 year
- Using CGM or isCGM (Flash Libre)
- HbA1c ≤ 9.0% (75 mmol/mol)
- Using carbohydrate counting
Who cannot join
- Allergy to glucagon or lactose
- Allergy to faster insulin aspart (FiAsp)
- Pheochromocytoma
- Self-reported lack of hypoglycemia symptoms when blood glucose is < 3.0 mmol/l
- Inability to follow study procedures, e.g. exercise, sleeping, blood sampling, and meal intake
- Pregnancy, nursing, plan to become pregnant or sexually active and not using adequate contraceptive methods (intrauterine device, contraceptive pill, patch or injection)
- Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during or within 30 days prior to study participation
- Other concomitant medical or psychological condition that according to the investigator's assessment makes the participant unsuitable for study participation
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Steno Diabetes Center Copenhagen
Gentofte Municipality, 2820
Herlev Hospital
Herlev, 2730
About this study
Objective:
To assess the efficacy and safety of an insulin-glucagon dual-hormone (DH) closed-loop system compared with an insulin-only single-hormone (SH) closed-loop system in adolescent with type 1 diabetes.
Methods:
In a 26-h, randomized, crossover, inpatient study, 20 children and adolescents with type 1 diabetes used two modes of the DiaCon Artificial Pancreas system: DH and SH closed-loop control. During each study period, participants will have one overnight stay, received three meals and performed exercise for 45 min (bicycle with estimated 50% V02max).
Endpoint:
The primary endpoint is sensor-derived percentage of time in hypoglycemia (<3.9 mmol/L).
Read the detailed description
Upon arrival at the research facility at Steno Diabetes Center Copenhagen, the participant's own pump and CGM are disconnected, and the two study pumps are attached. For dual-hormone control, the study pumps will be filled with FiAsp® and GlucaGen®. For single-hormone control, the study pumps have been filled with FiAsp® and isotonic saline.
In addition, participants are provided with a blinded wearable activity and sleep monitoring device (ActiGraph GT9X Link, Pensacola, FL) for activity level estimation and sleep assessment during study participation. The Actigraph is connected to a Bluetooth® Polar heart rate monitors during the exercise session.
Female participants deliver a urine sample for pregnancy testing. A sampling cannula is placed in an antecubital vein. The CGM will be calibrated with fingerpick glucose meter (Contour next®, Ascensia Diabetes Care) before initiating the closed-loop control. Even though it is not needed to calibrate the sensor, the accuracy of the sensor is better after one calibration.
At day 1 17:00 the study is initiated, and the closed-loop system takes over glucose control. Except from the control approach (single- vs. dual-hormone), the study days are identical. During the study visit, participants can move around freely, but they can only perform actual exercise during the stationary bike exercise session at day 2 16:30. At nighttime, the participants are encouraged to be in bed and, if possible, sleep.
At predefined timepoints, the investigators measure blood pressure and pulse, and the investigators ask the participants to rate their nausea level on a visual analog scale (VAS) from 1 to 100 to assess possible side effects of glucagon (vomiting rates as 100). In addition, the investigators ask them to self-rate blood glucose levels before bedtime (23:00), upon wake-up (07:00-08:00), before each meal, before exercise, and every 10 minutes during exercise.
Single-hormone and dual-hormone closed-loop control study sessions end 26 hours after study start. The study pumps and the CGMs are disconnected and the participants reconnect their own pumps and CGMs.
The two study sessions are separated by at least 36 hours.
- Conditions
- Type 1 Diabetes
- Being tested
- Glucagon, Closed-loop System
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Also called GlucaGen, Novo Nordisk,
Glucagon is filled in the pump and given automatically in case of hypoglycemia or pending hypoglycemia.
Closed-loop SystemDevice
Also called Saline
Closed-loop system comprise of two DANA RS (R) insulin pumps (FiAsp-GlucaGen vs FiAsp-saline), one DexCom G6 sensor, and a smartphone for the control algorithm.
| Study group | Role | What they receive |
|---|---|---|
| Dual-hormone Closed-loop | Active comparator | FiAsp® and GlucaGen®. Receives: Drug: Glucagon; Device: Closed-loop System |
| Single-Hormone Closed-loop | Placebo comparator | FiAsp® and isotonic saline. Receives: Device: Closed-loop System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of time with glucose values < 3.9 mmol/l as measured by the continuous glucose monitor
Percentage
Measured: 26 hours during closed-loop control
Secondary outcomes (21)
Number of carbohydrate interventions to treat hypoglycemia
Measured: 26 hours during closed-loop control
Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by continuous glucose monitor and plasma glucose
Percentage
Measured: 26 hours during closed-loop control
Percentage of time with glucose values < 3.9 mmol/l as measured by plasma glucose
Percentage
Measured: 26 hours during closed-loop control
Percentage of time with glucose values in the range > 13.9 mmol/l measured by continuous glucose monitor and plasma glucose
Percentage
Measured: 26 hours during closed-loop control
Percentage of time with glucose values < 3.0 mmol/l as measured by continuous glucose monitor and plasma glucose
Percentage
Measured: 26 hours during closed-loop control
Mean blood glucose value measured by continuous glucose monitor and plasma glucose
mmol/L
Measured: 26 hours during closed-loop control
Number of hypoglycemic episodes < 3.9 mmol/l on continuous glucose monitor and plasma glucose
No.
Measured: 26 hours during closed-loop control
Continuous glucose monitored glycemic variability measured as SD
mmol/L
Measured: 26 hours during closed-loop control
Continuous glucose monitored glycemic variability measured as CV
percentage
Measured: 26 hours during closed-loop control
Composite outcome: Percentage of participants achieving (1) time in range (3.9-10) > 70 %, (2) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (3) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by CGM and YSI
percentage
Measured: 26 hours during closed-loop control
Total insulin dose
units
Measured: 26 hours during closed-loop control
Total glucagon dose
mg
Measured: 26 hours during closed-loop control
Number of manual insulin boluses
No.
Measured: 26 hours during closed-loop control
Number of adverse events - Nausea
No of event if visual analog scale (0-100) increase >10 from baseline
Measured: 26 hours during closed-loop control
Number of adverse events - Headache
No of event if visual analog scale (0-100) increase >10 from baseline
Measured: 26 hours during closed-loop control
Number of adverse events - Palpitation
No of event if visual analog scale (0-100) increase >10 from baseline
Measured: 26 hours during closed-loop control
Number of vomits
No of event if visual analog scale (0-100) increase >10 from baseline
Measured: 26 hours during closed-loop control
Difference between actual and participant-estimated carbohydrate content in meals
g per meal
Measured: 26 hours of closed-loop glucose control
Mean Borg scale
Scale of perceived exertion from 6 (no effort activity) to 20 (max effort activity)
Measured: During 45 minutes exercise
Physical activity intensity measured by ActiGraph GT9X Link
Percentage of sedentary activity
Measured: 26 hours
Sleep efficiency measured by ActiGraph GT9X Link
The ratio of total sleep time to time in bed
Measured: 26 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start20 May 2021
- Primary completion26 Apr 2022
- Study completion26 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A randomized, single-blinded, cross-over study of glycemic control during dual-hormone therapy compared with single-hormone therapy in adolescents with type 1 diabetes.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Technical University of Denmark, Herlev Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04949867
- Sponsor's protocol ID
- H-21000207
- Other IDs
- 2020-005836-31, 2021-0409-34, PD002-19
- Acronym
- DHCL2021
- Status last verified
- Aug 2022
- First submitted
- 18 May 2021
- Last updated
- 18 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual-Hormone Closed-Loop Glucose Control in Adolescents With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04949867
- Acronym / sponsor ID
- DHCL2021 / H-21000207
- Conditions
- Type 1 Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- Technical University of Denmark, Herlev Hospital
- Study start
- 20 May 2021 (actual)
- Primary completion
- 26 Apr 2022 (actual)
- Study completion
- 26 Apr 2022 (actual)
- First posted
- 2 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective:
To assess the efficacy and safety of an insulin-glucagon dual-hormone (DH) closed-loop system compared with an insulin-only single-hormone (SH) closed-loop system in adolescent with type 1 diabetes.
Methods:
In a 26-h, randomized, crossover, inpatient study, 20 children and adolescents with type 1 diabetes used two modes of the DiaCon Artificial Pancreas system: DH and SH closed-loop control. During each study period, participants will have one overnight stay, received three meals and performed exercise for 45 min (bicycle with estimated 50% V02max).
Endpoint:
The primary endpoint is sensor-derived percentage of time in hypoglycemia (<3.9 mmol/L).
Detailed description
Upon arrival at the research facility at Steno Diabetes Center Copenhagen, the participant's own pump and CGM are disconnected, and the two study pumps are attached. For dual-hormone control, the study pumps will be filled with FiAsp® and GlucaGen®. For single-hormone control, the study pumps have been filled with FiAsp® and isotonic saline.
In addition, participants are provided with a blinded wearable activity and sleep monitoring device (ActiGraph GT9X Link, Pensacola, FL) for activity level estimation and sleep assessment during study participation. The Actigraph is connected to a Bluetooth® Polar heart rate monitors during the exercise session.
Female participants deliver a urine sample for pregnancy testing. A sampling cannula is placed in an antecubital vein. The CGM will be calibrated with fingerpick glucose meter (Contour next®, Ascensia Diabetes Care) before initiating the closed-loop control. Even though it is not needed to calibrate the sensor, the accuracy of the sensor is better after one calibration.
At day 1 17:00 the study is initiated, and the closed-loop system takes over glucose control. Except from the control approach (single- vs. dual-hormone), the study days are identical. During the study visit, participants can move around freely, but they can only perform actual exercise during the stationary bike exercise session at day 2 16:30. At nighttime, the participants are encouraged to be in bed and, if possible, sleep.
At predefined timepoints, the investigators measure blood pressure and pulse, and the investigators ask the participants to rate their nausea level on a visual analog scale (VAS) from 1 to 100 to assess possible side effects of glucagon (vomiting rates as 100). In addition, the investigators ask them to self-rate blood glucose levels before bedtime (23:00), upon wake-up (07:00-08:00), before each meal, before exercise, and every 10 minutes during exercise.
Single-hormone and dual-hormone closed-loop control study sessions end 26 hours after study start. The study pumps and the CGMs are disconnected and the participants reconnect their own pumps and CGMs.
The two study sessions are separated by at least 36 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- A randomized, single-blinded, cross-over study of glycemic control during dual-hormone therapy compared with single-hormone therapy in adolescents with type 1 diabetes.
| Arm | Type | Receives |
|---|---|---|
| Dual-hormone Closed-loop | Active comparator | Drug: Glucagon, Device: Closed-loop SystemFiAsp® and GlucaGen®. |
| Single-Hormone Closed-loop | Placebo comparator | Device: Closed-loop SystemFiAsp® and isotonic saline. |
Who may qualify
- Ages
- 13 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age = 13-17 years
- T1D duration ≥ 2 years
- Insulin pump therapy ≥ 1 year
- Using CGM or isCGM (Flash Libre)
- HbA1c ≤ 9.0% (75 mmol/mol)
Key exclusion criteria (8 listed)
- Allergy to glucagon or lactose
- Allergy to faster insulin aspart (FiAsp)
- Pheochromocytoma
- Self-reported lack of hypoglycemia symptoms when blood glucose is < 3.0 mmol/l
- Inability to follow study procedures, e.g. exercise, sleeping, blood sampling, and meal intake
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlucagonAlso: GlucaGen, Novo Nordisk,Glucagon is filled in the pump and given automatically in case of hypoglycemia or pending hypoglycemia. | Drug | Dual-hormone Closed-loop |
| Closed-loop SystemAlso: SalineClosed-loop system comprise of two DANA RS (R) insulin pumps (FiAsp-GlucaGen vs FiAsp-saline), one DexCom G6 sensor, and a smartphone for the control algorithm. | Device | Dual-hormone Closed-loop, Single-Hormone Closed-loop |
Primary outcome
Percentage of time with glucose values < 3.9 mmol/l as measured by the continuous glucose monitor
Time frame: 26 hours during closed-loop control
Percentage
21 secondary outcomes
Number of carbohydrate interventions to treat hypoglycemia
Time frame: 26 hours during closed-loop control
Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by continuous glucose monitor and plasma glucose
Time frame: 26 hours during closed-loop control
Percentage of time with glucose values < 3.9 mmol/l as measured by plasma glucose
Time frame: 26 hours during closed-loop control
Percentage of time with glucose values in the range > 13.9 mmol/l measured by continuous glucose monitor and plasma glucose
Time frame: 26 hours during closed-loop control
Percentage of time with glucose values < 3.0 mmol/l as measured by continuous glucose monitor and plasma glucose
Time frame: 26 hours during closed-loop control
Mean blood glucose value measured by continuous glucose monitor and plasma glucose
Time frame: 26 hours during closed-loop control
Number of hypoglycemic episodes < 3.9 mmol/l on continuous glucose monitor and plasma glucose
Time frame: 26 hours during closed-loop control
Continuous glucose monitored glycemic variability measured as SD
Time frame: 26 hours during closed-loop control
Continuous glucose monitored glycemic variability measured as CV
Time frame: 26 hours during closed-loop control
Composite outcome: Percentage of participants achieving (1) time in range (3.9-10) > 70 %, (2) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (3) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by CGM and YSI
Time frame: 26 hours during closed-loop control
Total insulin dose
Time frame: 26 hours during closed-loop control
Total glucagon dose
Time frame: 26 hours during closed-loop control
Number of manual insulin boluses
Time frame: 26 hours during closed-loop control
Number of adverse events - Nausea
Time frame: 26 hours during closed-loop control
Number of adverse events - Headache
Time frame: 26 hours during closed-loop control
Number of adverse events - Palpitation
Time frame: 26 hours during closed-loop control
Number of vomits
Time frame: 26 hours during closed-loop control
Difference between actual and participant-estimated carbohydrate content in meals
Time frame: 26 hours of closed-loop glucose control
Mean Borg scale
Time frame: During 45 minutes exercise
Physical activity intensity measured by ActiGraph GT9X Link
Time frame: 26 hours
Sleep efficiency measured by ActiGraph GT9X Link
Time frame: 26 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Individual participant dataSharing planned: Yes
Related trials for Type 1 Diabetes
Active, not recruitingPhase 3
Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
Type 1 Diabetes
RecruitingObservational study
Study of High Density Lipoprotein Function in Type 1 Diabetic Patients With Nephropathy
Type 1 Diabetes
Active, not recruitingPhase 1/2
A First-In-Human Study of ARO-INHBE in Adults With Obesity With and Without Type 2 Diabetes Mellitus
Obesity
RecruitingPhase 3
A Study to Evaluate Effect of AZD6234 in Adult Participants With Obesity or Overweight With Weight-related Comorbidity Without Type 2 Diabetes Mellitus
Obesity or Overweight
Not yet recruitingPhase 1/2
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Glucagon and Closed-loop System in people with Type 1 Diabetes, run by Steno Diabetes Center Copenhagen at 2 sites in Denmark.
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 6 inclusion and 8 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 18 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Percentage of time with glucose values < 3.9 mmol/l as measured by the continuous glucose monitor (time frame: 26 hours during closed-loop control). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Aug 2022.