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Effect of Different Plasma Insulin Levels on the Accuracy of Continuous Subcutaneous Glucose Monitoring

Primary Purpose

Type 1 Diabetes, Continuous Glucose Monitoring, Hypoglycemia

Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
High insulin eu-hypoglycemic clamp
Low insulin eu-hypoglycemic clamp
Sponsored by
Fundación para la Investigación del Hospital Clínico de Valencia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 1 Diabetes focused on measuring Interstitial glucose dynamics, Accuracy of continuous glucose monitoring under hypoglycemia, Glucose clamp

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

High plasma insulin-Low plasma insulin

Low plasma insulin-High plasma insulin

Arm Description

Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a High insulin glucose clamp and on the second day a Low insulin glucose clamp (sequence 'AB')

Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a Low insulin glucose clamp and on the second day a High insulin glucose clamp (sequence 'BA')

Outcomes

Primary Outcome Measures

Normalized current signal from the CGM devices
CGM devices are electrochemical sensors. Currently available sensors are placed in the subcutaneous tissue where they react with the glucose of the interstitial fluid giving a current signal (in nano Amperes), which is proportional to glucose concentrations. The current signal is then filtered and transformed into plasma glucose estimations through a calibration algorithm built into the CGM device. In this study we will analyze the current signal from CGM obtained under two different experimental conditions: Eu-hypoglycemic clamp with High plasma insulin concentrations Eu-hypoglycemic clamp with relatively Low plasma insulin concentrations This will allow for establishing the role, if any, of different plasma insulin concentrations on the accuracy of CGM to identify plasma glucose falls resulting in hypoglycaemia. Since CGM sensors can exhibit different sensitivities to glucose concentrations, the current signal will be normalized before statistical analysis

Secondary Outcome Measures

Full Information

First Posted
October 24, 2012
Last Updated
October 24, 2012
Sponsor
Fundación para la Investigación del Hospital Clínico de Valencia
Collaborators
Universitat Politècnica de València
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1. Study Identification

Unique Protocol Identification Number
NCT01714895
Brief Title
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

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación para la Investigación del Hospital Clínico de Valencia
Collaborators
Universitat Politècnica de València

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Continuous Glucose Monitoring, Hypoglycemia
Keywords
Interstitial glucose dynamics, Accuracy of continuous glucose monitoring under hypoglycemia, Glucose clamp

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High plasma insulin-Low plasma insulin
Arm Type
Other
Arm Description
Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a High insulin glucose clamp and on the second day a Low insulin glucose clamp (sequence 'AB')
Arm Title
Low plasma insulin-High plasma insulin
Arm Type
Other
Arm Description
Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a Low insulin glucose clamp and on the second day a High insulin glucose clamp (sequence 'BA')
Intervention Type
Other
Intervention Name(s)
High insulin eu-hypoglycemic clamp
Intervention Description
Primed intravenous insulin infusion at a rate of 1mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.
Intervention Type
Other
Intervention Name(s)
Low insulin eu-hypoglycemic clamp
Intervention Description
Primed intravenous insulin infusion at a rate of 0.3mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.
Primary Outcome Measure Information:
Title
Normalized current signal from the CGM devices
Description
CGM devices are electrochemical sensors. Currently available sensors are placed in the subcutaneous tissue where they react with the glucose of the interstitial fluid giving a current signal (in nano Amperes), which is proportional to glucose concentrations. The current signal is then filtered and transformed into plasma glucose estimations through a calibration algorithm built into the CGM device. In this study we will analyze the current signal from CGM obtained under two different experimental conditions: Eu-hypoglycemic clamp with High plasma insulin concentrations Eu-hypoglycemic clamp with relatively Low plasma insulin concentrations This will allow for establishing the role, if any, of different plasma insulin concentrations on the accuracy of CGM to identify plasma glucose falls resulting in hypoglycaemia. Since CGM sensors can exhibit different sensitivities to glucose concentrations, the current signal will be normalized before statistical analysis
Time Frame
330 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francisco Javier Ampudia-Blasco, MD, PhD
Organizational Affiliation
Hospital Clínico Universitario de Valencia - Fundación INCLIVA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
29638161
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.
Results Reference
derived

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Effect of Different Plasma Insulin Levels on the Accuracy of Continuous Subcutaneous Glucose Monitoring

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