Diabetes Mellitus, Type 1CL4M-ControlsNCT02100488
Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals
A study testing Closed-loop insulin infusion system and Open-loop insulin infusion system in people with Diabetes Mellitus, Type 1, run by Fundación para la Investigación del Hospital Clínico de Valencia at 2 sites in Spain.
Trial summary
Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. However, postprandial glucose control is a challenging issue in everyday diabetes care. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Closed-loop insulin infusion system and Open-loop insulin infusion system
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesSpain
- Study dates
- Mar 2014to Oct 2015
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects with type 1 diabetes mellitus
- Continuous subcutaneous insulin infusion (CSII) treatment for at least six months before Visit 1
- Body mass index of between 18 and 30 kg/m2
- HbA1c 6.0-8.5% at Visit 1
- Normal laboratory values, ECG, and vital signs unless the investigator considered an abnormality to be clinically irrelevant
- Women postmenopausal or using contraception judged by the investigator to be adequate (e.g., oral contraceptives, intra-uterine device or surgical treatment), or with a negative negative urine pregnancy tests at visits 1, 3 and 5
Who cannot join
- Pregnancy and lactation
- History of hypersensitivity to the study medications or to drugs with similar chemical structures
- Hypoglycaemia unawareness
- Progressive fatal diseases
- History of drug or alcohol abuse
- History of positive HIV or hepatitis B or C test
Show all 14Show fewer
- Impaired hepatic function, as shown by, but not limited to, SGPT or SGOT of more than twice the upper limit of the normal range at visit 1
- Impaired renal function, as shown by, but not limited to, serum creatinine > 1.5 mg/dL at visit 1
- Clinically relevant microvascular (pre-proliferative and proliferative retinopathy and macroalbuminuria), cardiovascular, hepatic, neurologic, endocrine or other major systemic diseases other than T1DM which could hinder implementation of the clinical study protocol or interpretation of the study results
- Pre-planned surgery during the study
- Blood donation of more than 500 ml during the past three months for men, or during the past six months for women
- Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
- Subject unlikely to comply with clinical study protocol, e.g., uncooperative attitude, inability to return for follow-up visits, or poor likelihood of completing the study
- Receipt of an experimental drug or use of an experimental device during the past 30 days.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Clínic i Universitari de Barcelona
Barcelona, 08036
Hospital Clínico Universitario de Valencia
Valencia, Valencia, 46010
About this study
Official title: Improving Postprandial Glycaemia by a New Developed Closed-loop Control System (Closedloop4meals). An Interdisciplinary, Investigator's Initiated Project for Optimization of Glucose Control in Type1 Diabetic Subjects
Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. However, postprandial glucose control is a challenging issue in everyday diabetes care. Indeed, excessive postprandial glucose excursions are the major contributors to plasma glucose (PG) variability in subjects with type 1 diabetes (T1DM). In addition, the poor reproducibility of postprandial glucose response is burdensome for patients and healthcare professionals.
Automatic glucose control, the so-called artificial pancreas or closed-loop system, may represent the ideal solution for reaching the therapeutic goals in diabetic patients. Intuitively, closed-loop insulin delivery may be superior to open-loop insulin delivery due to a better compensation of the variability of subcutaneous insulin absorption and the intra-subject insulin sensitivity. However, several challenges exist to effectively realize an optimal postprandial closed-loop control of blood glucose. Indeed, the eating process induces one of the major glucose perturbations that need to be controlled by an artificial pancreas and is currently one of the main challenges found in clinical validations of the few existing prototypes of an artificial pancreas. In particular, experiments carried out with the currently used algorithms for glucose control (the so called PID and MPC) showed that closed-loop insulin delivery often tend to overcorrect hyperglycemia thus increasing the risk hypoglycemia.
Read more
In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial pancreas') will be carried out in T1DM patients treated with continuous subcutaneous insulin infusion (CSII). The innovative element of the controller is a safety auxiliary feedback based on sliding mode reference conditioning (SMRC), which has been demonstrated (in simulation studies) to limit over-insulinization and the resulting hypoglycemia, reducing glycaemic variability.
Standardized meal test studies will be performed in T1DM subjects treated with CSII, comparing the administration of a classical bolus (open-loop study) with a controller-driven prandial insulin delivery (closed-loop study) based on continuous subcutaneous glucose monitoring (CGM).
The hypothesis is that closed loop control will provide better postprandial control, especially in terms of reduction of glucose variability and incidence of hypoglycemia.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Closed-loop insulin infusion system, Open-loop insulin infusion system
- Keywords
- Closed-loop insulin infusion, Postprandial glucose control, Glucose variability
- 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.
Closed-loop insulin infusion systemDevice
Also called CL4M Controls
Each subject will undergo two "Open-loop" and two "Closed-loop" meal tests, each one at 1-2 week intervals, thus completing the 4 experiments in about 6 weeks. The day of the experiment, a standard mixed meal test containing 60 g of carbohydrates (CHO), will be administered. On two occasions, patients will receive in a randomized order the standard insulin bolus based on the individual insulin to CHO ratio (First arm, Open-loop study). On the other two occasions they will receive a Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study). Commercial insulin infusion systems and continuous glucose monitoring devices will be used.
Open-loop insulin infusion systemOther
Standard subcutaneous insulin infusion based on the individual insulin to carbohydrate ratio. Commercial insulin infusion systems and continuous glucose monitoring devices will be used.
| Study group | Role | What they receive |
|---|---|---|
| Open-loop insulin infusion system | Active comparator | Standard Open-loop intensive insulin treatment with continuous insulin infusion (CSII). Commercially available insulin infusion systems will be used. Receives: Other: Open-loop insulin infusion system |
| Closed-loop insulin infusion system | Experimental | Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the by the software under investigation (CL4M Controls) based on blood glucose estimations from CGM. Receives: Device: Closed-loop insulin infusion system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-subject postprandial glycemic variability
Clinical validation of a new algorithm (glucose controller) for closed-loop control of postprandial glucose in comparison with a standard bolus (open-loop control), in type 1 diabetic subjects using insulin pump therapy. The robustness and effectiveness of the new algorithm for closed-loop glycaemic control (PID controller modified by SMRC-based external loop adjustments) will be evaluated through measurement of intra-subject postprandial glycemic variability expressed as the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) during the 8h post-prandial period (CV_AUC-PG_0-8h).
The hypothesis is that closed-loop insulin infusion reduces postprandial glucose variability as compared with standard treatment.
Measured: Eight-hour post-prandial period
Secondary outcomes (1)
CV_AUC-PG_3-8h
Coefficient of variation of the area under the curve (AUC) of plasma glucose (PG) during the late postprandial phase.
Measured: the 3-8 hour post-prandial interval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionJul 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de Valencia
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Universitat Politècnica de València, Universitat de Girona
- Responsible party
- Sponsor
- Investigators
- Francisco Javier Ampudia-Blasco, MD, PhD, Principal investigator, Department of Medicine, Division of Endocrinology and Nutrition, Clinic University Hospital of Valencia - Fundación INCLIVA, University of Valencia, Valencia, Spain.Ignacio Conget, MD, PhD, Principal investigator, Unidad de Diabetes. Servicio de Endocrinología y Nutrición, Hospital Clínic i Universitari de Barcelona, Barcelona, SpainJorge Bondia, PhD, Study director, University Institute of Control Systems and Industrial Computing (ai2 Institute), Polytechnic University of Valencia, Valencia, SpainJosep Vehí, PhD, Study director, Institute of Informatics and Applications, University of Girona, Girona, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100488
- Sponsor's protocol ID
- CL4M Controls
- Other IDs
- 470/13/EC
- Acronym
- CL4M-Controls
- Status last verified
- Nov 2015
- First submitted
- 27 Mar 2014
- Last updated
- 17 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Revert A, Garelli F, Pico J, De Battista H, Rossetti P, Vehi J, Bondia J. Safety auxiliary feedback element for the artificial pancreas in type 1 diabetes. IEEE Trans Biomed Eng. 2013 Aug;60(8):2113-22. doi: 10.1109/TBME.2013.2247602. Epub 2013 Feb 15.
PubMed 23428611Rossetti P, Quiros C, Moscardo V, Comas A, Gimenez M, Ampudia-Blasco FJ, Leon F, Montaser E, Conget I, Bondia J, Vehi J. Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technol Ther. 2017 Jun;19(6):355-362. doi: 10.1089/dia.2016.0443. Epub 2017 May 1.
PubMed 28459603
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Postprandial Glycaemia by a New Developed Closed-loop Control System (Closedloop4meals). An Interdisciplinary, Investigator's Initiated Project for Optimization of Glucose Control in Type1 Diabetic Subjects
- ClinicalTrials.gov ID
- NCT02100488
- Acronym / sponsor ID
- CL4M-Controls / CL4M Controls
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Closed-loop insulin infusion, Postprandial glucose control, Glucose variability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de ValenciaUniversity, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Universitat Politècnica de València, Universitat de Girona
- Study start
- Mar 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 1 Apr 2014 (estimated)
- 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.
Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. However, postprandial glucose control is a challenging issue in everyday diabetes care. Indeed, excessive postprandial glucose excursions are the major contributors to plasma glucose (PG) variability in subjects with type 1 diabetes (T1DM). In addition, the poor reproducibility of postprandial glucose response is burdensome for patients and healthcare professionals.
Automatic glucose control, the so-called artificial pancreas or closed-loop system, may represent the ideal solution for reaching the therapeutic goals in diabetic patients. Intuitively, closed-loop insulin delivery may be superior to open-loop insulin delivery due to a better compensation of the variability of subcutaneous insulin absorption and the intra-subject insulin sensitivity. However, several challenges exist to effectively realize an optimal postprandial closed-loop control of blood glucose. Indeed, the eating process induces one of the major glucose perturbations that need to be controlled by an artificial pancreas and is currently one of the main challenges found in clinical validations of the few existing prototypes of an artificial pancreas. In particular, experiments carried out with the currently used algorithms for glucose control (the so called PID and MPC) showed that closed-loop insulin delivery often tend to overcorrect hyperglycemia thus increasing the risk hypoglycemia.
In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial pancreas') will be carried out in T1DM patients treated with continuous subcutaneous insulin infusion (CSII). The innovative element of the controller is a safety auxiliary feedback based on sliding mode reference conditioning (SMRC), which has been demonstrated (in simulation studies) to limit over-insulinization and the resulting hypoglycemia, reducing glycaemic variability.
Standardized meal test studies will be performed in T1DM subjects treated with CSII, comparing the administration of a classical bolus (open-loop study) with a controller-driven prandial insulin delivery (closed-loop study) based on continuous subcutaneous glucose monitoring (CGM).
The hypothesis is that closed loop control will provide better postprandial control, especially in terms of reduction of glucose variability and incidence of hypoglycemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open-loop insulin infusion system | Active comparator | Other: Open-loop insulin infusion systemStandard Open-loop intensive insulin treatment with continuous insulin infusion (CSII). Commercially available insulin infusion systems will be used. |
| Closed-loop insulin infusion system | Experimental | Device: Closed-loop insulin infusion systemSliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the by the software under investigation (CL4M Controls) based on blood glucose estimations from CGM. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subjects with type 1 diabetes mellitus
- Continuous subcutaneous insulin infusion (CSII) treatment for at least six months before Visit 1
- Body mass index of between 18 and 30 kg/m2
- HbA1c 6.0-8.5% at Visit 1
- Normal laboratory values, ECG, and vital signs unless the investigator considered an abnormality to be clinically irrelevant
Key exclusion criteria (14 listed)
- Pregnancy and lactation
- History of hypersensitivity to the study medications or to drugs with similar chemical structures
- Hypoglycaemia unawareness
- Progressive fatal diseases
- History of drug or alcohol abuse
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 |
|---|---|---|
| Closed-loop insulin infusion systemAlso: CL4M ControlsEach subject will undergo two "Open-loop" and two "Closed-loop" meal tests, each one at 1-2 week intervals, thus completing the 4 experiments in about 6 weeks. The day of the experiment, a standard mixed meal test containing 60 g of carbohydrates (CHO), will be administered. On two occasions, patients will receive in a randomized order the standard insulin bolus based on the individual insulin to CHO ratio (First arm, Open-loop study). On the other two occasions they will receive a Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study). Commercial insulin infusion systems and continuous glucose monitoring devices will be used. | Device | Closed-loop insulin infusion system |
| Open-loop insulin infusion systemStandard subcutaneous insulin infusion based on the individual insulin to carbohydrate ratio. Commercial insulin infusion systems and continuous glucose monitoring devices will be used. | Other | Open-loop insulin infusion system |
Primary outcome
Intra-subject postprandial glycemic variability
Time frame: Eight-hour post-prandial period
Clinical validation of a new algorithm (glucose controller) for closed-loop control of postprandial glucose in comparison with a standard bolus (open-loop control), in type 1 diabetic subjects using insulin pump therapy. The robustness and effectiveness of the new algorithm for closed-loop glycaemic control (PID controller modified by SMRC-based external loop adjustments) will be evaluated through measurement of intra-subject postprandial glycemic variability expressed as the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) during the 8h post-prandial period (CV_AUC-PG_0-8h). The hypothesis is that closed-loop insulin infusion reduces postprandial glucose variability as compared with standard treatment.
1 secondary outcome
CV_AUC-PG_3-8h
Time frame: the 3-8 hour post-prandial interval
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 17 Nov 2015.
- Background: PubMed 23428611Revert A, Garelli F, Pico J, De Battista H, Rossetti P, Vehi J, Bondia J. Safety auxiliary feedback element for the artificial pancreas in type 1 diabetes. IEEE Trans Biomed Eng. 2013 Aug;60(8):2113-22. doi: 10.1109/TBME.2013.2247602. Epub 2013 Feb 15.
- Derived from this study: PubMed 28459603Rossetti P, Quiros C, Moscardo V, Comas A, Gimenez M, Ampudia-Blasco FJ, Leon F, Montaser E, Conget I, Bondia J, Vehi J. Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technol Ther. 2017 Jun;19(6):355-362. doi: 10.1089/dia.2016.0443. Epub 2017 May 1.
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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.
Francisco Javier Ampudia-Blasco, MD, PhD principal investigator
Department of Medicine, Division of Endocrinology and Nutrition, Clinic University Hospital of Valencia - Fundación INCLIVA, University of Valencia, Valencia, Spain.
Ignacio Conget, MD, PhD principal investigator
Unidad de Diabetes. Servicio de Endocrinología y Nutrición, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
Jorge Bondia, PhD study director
University Institute of Control Systems and Industrial Computing (ai2 Institute), Polytechnic University of Valencia, Valencia, Spain
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Closed-loop insulin infusion system and Open-loop insulin infusion system in people with Diabetes Mellitus, Type 1, run by Fundación para la Investigación del Hospital Clínico de Valencia at 2 sites in Spain.
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 14 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 17 Nov 2015. 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 Spain. 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?
Intra-subject postprandial glycemic variability (time frame: Eight-hour post-prandial period). 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 NCT02100488, which also lists 2 linked publications.
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 17 Nov 2015.