- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04053712
Dual-hormone Closed-loop Glucose Control in Type 1 Diabetes (DHCL2019)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Rationale: We hypothesize that our newly developed dual-hormone insulin-glucagon closed-loop system (DCL) is safe, efficient and superior to our single-hormone insulin-only closed-loop system (SCL). The study aims to compare the glucose control achieved by DCL with our SCL.
Design: A randomized single-blinded placebo-controlled cross-over 33-hour in-clinic study of glucose control achieved with DCL versus SCL in adults and adolescents with type 1 diabetes.
Participants: 13 insulin-pump treated T1D participants will be included, if they are 15-80 years old, have T1D for ≥ 3 years, use insulin pumps with FiAsp®, and have an HbA1c≤ 8.5% (69 mmol/mol).
Procedures: In this two-phase study 1) we test the operability of our closed-loop systems and 2) compare glucose control by DCL with SCL. The two studies are identical except for the blinding procedures. In the first phase (pilot study), four participants are included, and the glucagon/saline pump is not masked. In the second phase (main study), 13 participants are included, and are as well as the investigators blinded for the content in the glucagon/saline pump.
Two days prior to study visit, a CGM (Dexcom® G6) is place on the participant's abdomen. At study visits, participants arrive in the evening at our research unit and get their insulin pump disconnected. Two study pumps (Dana Diabecare RS®, SOOIL) are attached: one pump infuses insulin (FiAsp®, Novo Nordisk) and the other infuses either glucagon (GlucaGen®, Novo Nordisk) or saline. Once a sampling cannula is placed in an antecubital vein, the study is initiated and the closed-loop system (DCL vs SCL) takes over the glucose control for the next 33 hours. Except from the control algorithm (SCL vs DCL), the study days are identical. Participants can move around freely in the clinic for 33 hours but will perform a 45-min moderate (50% VO2max) exercise session, consume three meals with variant carbohydrate content, and sleep during two overnight periods. Participants will be monitored frequently with blood samples (drawn from the antecubital vein), blood pressure, pulse, and VAS scale for nausea.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Gentofte, Denmark
- Steno Diabetes Center Copenhagen
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria
- Age ≥ 18 years
- T1D ≥ 2 years
- Insulin pump therapy ≥ 1
- Currently treated with FiAsp® - insulin
- HbA1c ≤ 8.5% (69 mmol/mol) Exclusion criteria
- Pregnancy or nursing
- Inability and willingness to comply with all protocol procedures, e.g. exercise, sleeping, blood sampling, and meal consumption
- Plan to become pregnant or sexually active and not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection)
- Hypoglycemia unawareness (self-reported lack of hypoglycemia symptoms when blood glucose is < 3.0 mmol/l)
- Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during or within 30 days prior to study participation
- History of coronary artery disease or congestive heart failure
- Abnormal ECG suggestive of coronary artery disease and increased risk of malignant arrhythmia
- Allergy to glucagon or lactose
- Pheochromocytoma
- Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation
Withdrawal criteria
- In case of pregnancy (or desire for pregnancy), female subjects are withdrawn
- Lack of compliance to any of the important study procedures in the discretion of the investigator
- Unacceptable adverse effects in the discretion of the investigator
- Withdrawal on participants request will be accepted at any time without further justification
Patients who complete or withdraw from the study continue their usual quarterly follow-up visits at the diabetes clinic. Withdrawal does not affect their statutory patient rights.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Single-hormone
FiAsp (R) - 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.
|
ACTIVE_COMPARATOR: Dual-hormone
FiAsp(R) - GlucaGen(R)
|
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.
GlucaGen(R), Novo Nordisk, DK
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of time with glucose values < 3.9 mmol/l as measured by glucose sensor
Time Frame: 33 hours
|
33 hours
|
|
Number of carbohydrate interventions to treat hypoglycemia
Time Frame: 33 hours
|
Carbohydrate interventions are predefined and provided in case of hypoglycemia
|
33 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of time with glucose values < 3.9 mmol/l as measured by venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of participants achieving (A) time in range (3.9-10 mmol/l) > 70 %, (B) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (C) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
A composite outcome will be calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Mean blood glucose value measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of time with glucose values in the range 3.9-8.0 mmol/l measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of time with glucose values in the range > 13.9 measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of time with glucose values < 3.0 mmol/l as measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Number of hypoglycemic episodes (<3.9 mmol/l and <3.0 mmol/l) overnight and during daytime
Time Frame: 33 hours
|
33 hours
|
|
Nadir blood glucose value for each hypoglycemic episode as measured by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
33 hours
|
|
Glucose sensor glycemic variability measured as SD and CV during overnight and during daytime
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Low Blood Glucose Index (LBGI) overnight and during daytime by glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Percentage of participants with a mean blood glucose value (glucose sensor and venous plasma glucose) ≤ 8.6 mmol/l (corresponding to an estimated HbA1c of 7.0% / 53 mmol/mol)
Time Frame: 33 hours
|
33 hours
|
|
Percentage of patients with a mean blood glucose value (glucose sensor and venous plasma glucose) ≤ their standard therapy mean glucose value (calculated based on HbA1c measurement)
Time Frame: 33 hours
|
33 hours
|
|
Mean Absolute Relative Difference (MARD) between glucose sensor and venous plasma glucose
Time Frame: 33 hours
|
Participants have two glucose sensors during the study
|
33 hours
|
Percentages of values between glucose sensor and venous plasma glucose in zone A, B, C, D and E in the Clarke Error Grid analysis.
Time Frame: 33 hours
|
Participants have two glucose sensors during the study.
One sensor closed to the infusion of glucagon.
|
33 hours
|
Mean blood pressure over the study period (mmHG)
Time Frame: 33 hours
|
Blood pressure and pulse taken at predefined timepoints
|
33 hours
|
Mean pulse rate over the study period (beats per min)
Time Frame: 33 hours
|
Blood pressure and pulse taken at predefined timepoints
|
33 hours
|
Mean nausea level measured with a visual analog scale (VAS range: 0-10)
Time Frame: 33 hours
|
Calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Total insulin dose per study day (UI)
Time Frame: 33 hours
|
33 hours
|
|
Total time of insulin suspension per study day (UI)
Time Frame: 33 hours
|
33 hours
|
|
Total glucagon dose per study day (microgram)
Time Frame: 33 hours
|
the outcome will be calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Mean plasma glucagon
Time Frame: 33 hours
|
the outcome will be calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Mean plasma insulin aspart
Time Frame: 33 hours
|
the outcome will be calculated for the whole study period as well as for the following intervals: night 1 (23:00-07:00), night 2 (23:00-07:00), night 1 and 2, 23:00-15:00 and 15:00-07:00.
|
33 hours
|
Difference in participant estimated grams of carbohydrate and actual carbohydrate in study meals
Time Frame: 33 hours
|
Meals presented at the study will be estimated for carbohydrate content by the participant on
|
33 hours
|
Difference in participant estimated blood glucose level and plasma glucose level at predefined timepoints
Time Frame: 33 hours
|
Self-assessment of glucose levels (Clarke Error Grid)
|
33 hours
|
Total energy expenditure during the study visit (kcal/kg) measured by ActiGraph GT9X Link
Time Frame: 33 hours
|
Freedson and Sasaki MET prediction equations to determine energy expenditure in MET
|
33 hours
|
Steps taken during the study visit measured by ActiGraph GT9X Link
Time Frame: 33 hours
|
33 hours
|
|
Minutes per study day (min/d) spent in different levels of activity (sedentary, light, moderate, vigorous, or MVPA) measured by ActiGraph GT9X Link
Time Frame: 45 min
|
45 min
|
|
Minutes between lights off and the first sleep episode (Sleep latency) measured by ActiGraph GT9X Link
Time Frame: 14 hours
|
14 hours
|
|
Total sleep time measured by ActiGraph GT9X Link
Time Frame: 14 hours
|
Minutes between sleep onset and wake time
|
14 hours
|
The percentage of time asleep from lights off to lights on (sleep efficiency) measured by ActiGraph GT9X Link
Time Frame: 14 hours
|
14 hours
|
|
Mean Borg scale level during exercise (RANGE:0-10)
Time Frame: 45 min
|
Assessed every 5-10 minutes during bicycling
|
45 min
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ajenthen G Ranjan, MD, PhD, Steno Diabetes Center Copenhagen
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Hypoglycemia
- Physiological Effects of Drugs
- Gastrointestinal Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Glucagon
Other Study ID Numbers
- H-19026331
- 2019-001631-31 (EUDRACT_NUMBER)
- 2019043528 (REGISTRY: Danish Medical Agency)
- 2019043269 (REGISTRY: Danish Medical Agency - Device regulation)
- CIV-19-04-028465 (REGISTRY: CIV ID)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypoglycemia
-
University of California, San DiegoDexCom, Inc.Recruiting
-
Vogenx, Inc.Active, not recruitingPostbariatric HypoglycemiaUnited States
-
Joslin Diabetes CenterDexCom, Inc.CompletedHypoglycemia | Hypoglycemia, ReactiveUnited States
-
Nutricia ResearchCompletedPostprandial HypoglycemiaNetherlands
-
PediatrixBanner University Medical CenterTerminatedEffects of a Hypoglycemia Protocol With Glucose Gel on Neonatal Intensive Care Unit (NICU) AdmissionHypoglycemia | Neonatal HypoglycemiaUnited States
-
Tel-Aviv Sourasky Medical CenterUnknown
-
University of UlmRecruitingHypoglycemia, ReactiveGermany
-
University of ArizonaNot yet recruiting
-
Milton S. Hershey Medical CenterDexCom, Inc.; Children's Miracle NetworkRecruiting
-
Zealand University HospitalUnknownHypoglycemia, ReactiveDenmark
Clinical Trials on Closed-loop system
-
Centre Hospitalier du LuxembourgUniversity of Cambridge; Luxembourg Institute of HealthCompletedType1 Diabetes MellitusLuxembourg
-
Medtronic DiabetesWithdrawn
-
Rabin Medical CenterCompleted
-
Azienda Ospedaliera Cardinale G. PanicoCompletedSyncope, Vasovagal, Neurally-MediatedItaly
-
Rabin Medical CenterMedtronicCompleted
-
University of California, IrvineCompletedPostoperative Complications | Intraoperative Volume StatusUnited States
-
Stanford UniversityCompleted
-
DiabeloopUniversity Hospital, Grenoble; AGIR à Dom; Icadom; Centre Hospitalier Annecy Genevois and other collaboratorsCompletedDiabetes Mellitus Type 2 - Insulin-TreatedFrance
-
University of VirginiaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedType 1 DiabetesUnited States
-
University of MalayaNot yet recruitingARDS | Ventilator-Induced Lung Injury | Mechanical Ventilation Complication | Ventilator Lung