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Completed

NCT Number: NCT03577158

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

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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Behavior Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Immune System Diseases Insulin Resistance Metabolic Diseases Motor Activity Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Closed-loop controller with exercise mitigation module

Device

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.

Closed-loop controller without exercise mitigation module

Device

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.

Open-loop insulin infusion system

Device

Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Hospital Clinic of Barcelona

Other

Collaborators

  • Universitat Politècnica de València
  • Universitat de Girona

Registry information

Acronym: SAFE-AP3

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jul 5, 2018
Registry last updated
Aug 7, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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