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Trial record 57 of 668 for:    diabetes AND Hypoglycemic | Recruiting, Not yet recruiting, Available Studies

SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise (SAFE-AP3)

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ClinicalTrials.gov Identifier: NCT03577158
Recruitment Status : Recruiting
First Posted : July 4, 2018
Last Update Posted : July 10, 2018
Sponsor:
Collaborators:
Universitat Politècnica de València
Universitat de Girona
Information provided by (Responsible Party):
Ignacio Conget, Hospital Clinic of Barcelona

Brief Summary:

Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. Despite growing evidence about the health benefits of regular exercise in diabetes, exercise-associated glycemic imbalance remains a challenge in subjects with type 1 diabetes (T1D) due to a higher risk of hypoglycemia.

Automatic glucose control, the so-called artificial pancreas (AP) 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 closed-loop control of blood glucose during exercise. Indeed, the physical exercise 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 (proportional-integrative-derivative) and MPC) showed that closed-loop insulin delivery is deteriorated by exercise, increasing the risk of hypoglycemia even with pre-exercise carbohydrate ingestion when non-announcement strategies are used.

In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial pancreas') will be carried out in T1D 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 to limit over-insulinization and the resulting hypoglycemia, reducing glycaemic variability.

Announced and unannounced exercise will be performed in T1D subjects treated with CSII, comparing the number of hypoglycemic episodes with a controller-driven insulin delivery (closed-loop study) based on continuous subcutaneous glucose monitoring (CGM).

If any glucose value <70 mg/dL 15 gr of glucose will be provided. Moreover 15gr of glucose will be provided in AP studies when AP system recommends it.

The hypothesis is that closed loop control will provide better glycemic control, with less hypoglycemia episodes.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Device: Closed-loop controller with exercise mitigation module Device: Closed-loop controller without exercise mitigation module Device: Open-loop insulin infusion system Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Longitudinal, prospective, interventional study.
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : May 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Closed-loop controller with exercise mitigation module

Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with mitigation module.

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 software under investigation (SAFEAP with mitigation module) based on blood glucose estimations from CGM.

Device: Closed-loop controller with exercise mitigation module

Each subject will undergo three exercise tests, each one at 1-2 week intervals, thus completing the 3 experiments in about 6 weeks. The day of the experiment, the participant will do 3 sets of 15 minutes of cycloergometer at 70% of VO2max with 5 minutes of rest between them. On the first arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with a mitigation mode, based on subcutaneous continuous glucose monitoring (First arm, Closed-loop study with mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Closed-loop controller without exercise mitigation module

On the second arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration without a mitigation mode, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study without mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Open-loop insulin infusion system
Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.

Experimental: Closed-loop controller without exercise mitigation module
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 software under investigation (SAFEAP without mitigation module) based on blood glucose estimations from CGM.
Device: Closed-loop controller with exercise mitigation module

Each subject will undergo three exercise tests, each one at 1-2 week intervals, thus completing the 3 experiments in about 6 weeks. The day of the experiment, the participant will do 3 sets of 15 minutes of cycloergometer at 70% of VO2max with 5 minutes of rest between them. On the first arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with a mitigation mode, based on subcutaneous continuous glucose monitoring (First arm, Closed-loop study with mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Closed-loop controller without exercise mitigation module

On the second arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration without a mitigation mode, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study without mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Open-loop insulin infusion system
Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.

Active Comparator: Open-loop insulin infusion system
Standard Open-loop intensive insulin treatment with continuous subcutaneous insulin infusion (CSII). Commercially available insulin infusion systems will be used.
Device: Closed-loop controller with exercise mitigation module

Each subject will undergo three exercise tests, each one at 1-2 week intervals, thus completing the 3 experiments in about 6 weeks. The day of the experiment, the participant will do 3 sets of 15 minutes of cycloergometer at 70% of VO2max with 5 minutes of rest between them. On the first arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with a mitigation mode, based on subcutaneous continuous glucose monitoring (First arm, Closed-loop study with mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Closed-loop controller without exercise mitigation module

On the second arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration without a mitigation mode, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study without mitigation module).

Commercial insulin infusion systems and continuous glucose monitoring devices will be used.


Device: Open-loop insulin infusion system
Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.




Primary Outcome Measures :
  1. Number of hypoglycaemias [ Time Frame: 180 minutes psot-exercise period ]
    Number of hypoglycemic episodes (defined as plasma glucose (PG) <70mg/dL) during exercise and recovery.


Secondary Outcome Measures :
  1. AUC (area under curve) of PG during exercise and recovery [ Time Frame: 180 minutes post-exercise period ]
    AUC0_180min, AUC0_60min and AUC60_180min of PG and time spent in different glycemic ranges (< 70; 70-180; > 180 mg/dL) during exercise and recovery.

  2. AUC of SG during exercise and recovery [ Time Frame: 180 minutes post-exercise period ]
    AUC0-180min, AUC0-60min and AUC60-180min of sensor glucose (SG) and time spent in different glycemic ranges (< 70; 70-180; > 180 mg/dL) during exercise and recovery.

  3. Rate-of-change of glucose during exercise (ROCe) and recovery (ROCr) [ Time Frame: 180 minutes post-exercise period ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18-65 years.
  • Under CSII treatment for at least six months before visit 1.
  • Body mass index between 18 and 30 kg/m2.
  • HbA1c 6.0-8.5% at visit 1.
  • Physical examination, laboratory data and EKG without alterations. Abnormalities considered clinically irrelevant by the investigator will not be exclusion criteria.
  • Postmenopausal women or women of childbearing age using contraceptives of proven effectiveness and with negative urine pregnancy test at screening visit.

Exclusion Criteria:

  • Pregnancy and breastfeeding.
  • Hypoglycemia unawareness (Clarke Test >3).
  • Progressive fatal disease.
  • History of drug or alcohol abuse.
  • History HIV positive, active hepatitis B or hepatitis C.
  • Impaired liver function, as shown in, but not limited to, SGPT (serum gutamate pyruvate transaminase) or SGOT (serum glutamate oxaloacetate transaminase) more than twice the upper limit of normal at Visit 1.
  • Clinically relevant microvascular complications (macroalbuminuria, pre-proliferative and proliferative retinopathy), cardiovascular, hepatic, neurological, endocrine or other systematic, apart from T1D, which may hamper the implementation of the clinical study protocol or interpretation of results study.
  • Scheduled surgery during the study period.
  • Mental conditions that prevent the subject to understand the nature, purpose and possible consequences of the study.
  • Subjects those are unlikely to meet the clinical study protocol, eg uncooperative attitude, inability to return for follow-up visits, or poor probability of completing the study.
  • Using an experimental drug or device during the past 30 days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03577158


Contacts
Contact: Ignacio Conget Donlo, MD 932279846 iconget@clinic.cat
Contact: Clara Viñals Domenech, MD +34659985895 vinals@clinic.cat

Locations
Spain
Hospital Clínic de Barcelona Recruiting
Barcelona, Catalonia, Spain, 08036
Contact: Ignacio Conget Donlo, MD    932279846    iconget@clinic.cat   
Principal Investigator: Marga Giménez Álvarez, MD         
Sub-Investigator: Clara Viñals Domenech, MD         
Sponsors and Collaborators
Hospital Clinic of Barcelona
Universitat Politècnica de València
Universitat de Girona
Investigators
Study Director: Jorge Bondia, PhD Universitat Politècnica de València
Study Director: Josep Vehi, PhD Universitat de Girona
Study Director: Ignacio Conget Donlo, MD Hospital Clínic de Barcelona
Study Chair: Marga Gimenez Alvarez, MD Hospital Clínic de Barcelona

Additional Information:
Publications:
Responsible Party: Ignacio Conget, Head of Endocrinology and Nutrition Department, Principal Investigator, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT03577158     History of Changes
Other Study ID Numbers: SAFE-AP3
First Posted: July 4, 2018    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ignacio Conget, Hospital Clinic of Barcelona:
Diabetes Mellitus, Type 1
Insulin
Exercise
Closed-loop
Artificial Pancreas

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemic Agents
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Physiological Effects of Drugs