Clinical trial NCT01714895: Effect of Different Plasma Insulin Levels on the Accuracy of Continuous Subcutaneous Glucose Monitoring
Official title: New Strategies for Automated Glycaemic Control: the Issue of Continuous Glucose Monitoring Accuracy Under Hypoglycaemic Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Continuous Glucose Monitoring
Hypoglycemia
Keywords: Interstitial glucose dynamics
Accuracy of continuous glucose monitoring under hypoglycemia
Glucose clamp
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
Collaborators: name: Universitat Politècnica de València
First posted: 2012-10-26
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Achieving near-normoglycaemia has been established as the main objective for most patients with diabetes. However, it is well known that intensification of treatment is associated with an increase in the frequency of hypoglycemia, especially in the context of insulin therapy. The burden of hypoglycemia in terms of psychological implications, morbidity and even mortality, explains why it has been defined as the main limiting factor to achievement of good metabolic control.

Continuous subcutaneous glucose monitoring (CGM) devices have been claimed to be useful in hypoglycemia detection/prevention, allowing theoretically for safer intensification of therapy in diabetic patients. However, accuracy of CGM devices, especially in the hypoglycemic range, raises some concerns. In fact, commercially available CGM devices estimate plasma glucose from measurements in the interstitial fluid and not in plasma. However, the relationship between plasma and interstitial glucose is not fully understood, especially under dynamic conditions, and this may explain the poor CGM performance during rapid changes in blood glucose and hypoglycemia.

In this project, the relationship between plasma and interstitial glucose will be evaluated under conditions of normal glucose concentrations and hypoglycemia. Experiments will be performed to assess the role, if any, of different plasma insulin concentrations on the accuracy of CGM.

All the information obtained may be relevant to the improvement of the ability of CGM devices to detect hypoglycemia and hypoglycemic risk.


Eligibility criteria: Inclusion Criteria:

* Subjects with type 1 diabetes mellitus meeting all of the following criteria will be considered for admission to the study:

  * Aged between 18 and 60 years
  * Under CSII or MDI 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)

Exclusion Criteria:

* Subjects meeting any of the following criteria will not be included in the study:

  * Pregnancy and lactation
  * History of hypersensitivity to the study medications or to drugs with similar chemical structures
  * Confirmed hypoglycaemia unawareness
  * Progressive fatal diseases
  * History of drug or alcohol abuse
  * History of positive HIV or hepatitis B or C test
  * 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, 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.

Primary outcomes:
measure: Normalized current signal from the CGM devices
timeFrame: 330 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Hospital Clínico Universitario de Valencia - Fundación INCLIVA
name: Francisco Javier Ampudia-Blasco, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moscardo V, Bondia J, Ampudia-Blasco FJ, Fanelli CG, Lucidi P, Rossetti P. Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration. Diabetes Technol Ther. 2018 Apr;20(4):263-273. doi: 10.1089/dia.2017.0219. Epub 2018 Mar 12.