Mixed Meal Test in Type 1 Diabetes on Insulin Pump Therapy: Optimization of Artificial Pancreas
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|ClinicalTrials.gov Identifier: NCT02003274|
Recruitment Status : Unknown
Verified March 2017 by Azienda Ospedaliera Universitaria Integrata Verona.
Recruitment status was: Active, not recruiting
First Posted : December 6, 2013
Last Update Posted : July 2, 2017
BACKGROUND. Optimal glucose control can prevent/relent tissue damage in patients with type 1 diabetes mellitus (T1DM). Ongoing efforts aim at developing closed loop control (CLC) algorithms linking subcutaneous continuous glucose monitoring (CGM) and insulin delivery (CSII). Substantial improvement towards an effective artificial pancreas system is still needed, especially in the regulation of post-meal glucose. Application of metabolic control analysis (MCA) can unveil and quantify distortions in the system properties of the glucose-insulin (pump) system (GIS), by measuring the coefficients of control (CCs) of glucose. Our approach rely on previous experience with our previous pilot protocol (NCT01800734).
AIM. We will outline and compare features of GIS in T1DM patients and in healthy controls during differently sized breakfast meals and during 24-hour periods. The reproducibility of our approach will also be assessed.
METHODOLOGY. Three protocols will be carried out. All T1DM patients will be on CGM/CSII therapy. In all three protocols, study 1 will be an euglycemic insulin clamp in T1DM patients and a frequently sampled intravenous glucose tolerance test (IVGTT) in healthy controls.
- Protocol 1: 10 T1DM patients on CGM/CSII and 10 control subjects will ingest a mixed meal of different size (320 and 640 kcal) on two separate occasions.
- Protocol 2: 5 T1DM patients will ingest two repeat 320 kcal meals, whereas other 5 T1DM patients will ingest two 640 kcal meals on two separate occasions.
- Protocol 3: 10 T1DM patients and 10 controls will be monitored for 24 hours, during which they will ingest 3 mixed meals.
Substrate (including CGM)/hormone responses will be measured in all studies. Comprehensive single meal and 24-hour models of GIS will be built, MCA will be applied and the CCs of glucose assessed, thereby allowing to outline and to compare the CCs of glucose between patients and controls.
EXPECTED RESULTS. Our data will be of use in devising novel clinical strategies in T1DM, including, but not limited to, development and refinement of CLC algorithms along the path towards an effective artificial pancreas system.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Other: Clamp-Mixed Meal Other: IVGTT-Mixed Meal Arm||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Meal Glucose Regulation in Type 1 Diabetes on Insulin Pump Therapy: Towards a Better Understanding of the Glucose-Insulin System.|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||October 2016|
|Estimated Study Completion Date :||October 31, 2017|
Clamp-Mixed Meal Arm
Twenty adult patients with type 1 diabetes, regularly attending the Division of Endocrinology and Metabolic Diseases of University of Verona School of Medicine, using continuous subcutaneous fast insulin analogue infusion (CSII) through a permanent pump and on subcutaneous glucose sensing will be enrolled.
Other: Clamp-Mixed Meal
Standard clinical parameters will be assessed in all patients.
A. Euglycemic insulin clamp. A standard euglycemic insulin clamp will be carried out in type 1 diabetic patients to assess insulin sensitivity, as previously described (1).
B. Mixed meal test. All participants will ingest a standardized mixed meal and will be monitored for 300 minutes thereafter. Right before meal ingestion, a s.c. fast insulin analogue bolus will be administered by the pump
This test will determine the time courses of:
1. plasma glucose, 2. 13C/12C glucose ratio (hence, meal-derived and endogenous glucose), 3. insulin, 4. free fatty acids, 5. aminoacids, 6. glucagon, 7. incretin hormones 8. glucose control coefficients (CCs) during a mixed meal.
IVGTT-Mixed Meal Arm
Twenty healthy adult volunteers will be recruited.
Other: IVGTT-Mixed Meal Arm
Standard clinical parameters will be assessed in all subjects.
A. IVGTT. A frequently sampled intravenous glucose tolerance test (IVGTT) in healthy controls will be carried out in study 1 and study 3 to assess insulin sensitivity.
B. Mixed meal test. All participants will ingest a standardized mixed meal and will be monitored for 300 minutes thereafter.
This test will determine the time courses of:
1. plasma glucose, 2.13C/12C glucose ratio (hence, meal-derived and endogenous glucose), 3. insulin, 4. free fatty acids, 5. aminoacids, 6. glucagon, 7. incretin hormones 8. glucose control coefficients (CCs) during a mixed meal.
- 1. Composite plasma glucose and hormone responses to a mixed meal; 2. Glucose control coefficients [ Time Frame: 24 months ]
- Timed curves of composite plasma glucose, meal-derived glucose, endogenous glucose, insulin, glucagon and incretin hormone concentrations in response to a mixed meal.
- Composite glucose control coefficients (CCs) of each component of the glucose-insulin system at each time point of the mixed meal.
- Composite plasma free fatty and amino acid responses to a mixed meal [ Time Frame: 24 months ]Composite timed curves of plasma free fatty and amino acid concentrations to a mixed meal.
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): NCT02003274
|Clinical Research Center-University Hospital of Verona|
|c/o Policlinico G.B. Rossi - Piazzale L.A. Scuro, 10, Verona, Italy, 37134|
|Division of Endocrinology and Metabolic Diseases - University Hospital of Verona|
|Piazzale Stefani 1-Pad. 22, Verona, Italy, 37126|
|Principal Investigator:||Riccardo C Bonadonna, Assoc Prof||Division of Endocrinology and Metabolic Diseases, University Hospital of Verona|
|Study Director:||Enzo Bonora, Full Prof||Division of Endocrinology and Metabolic Diseases, University Hospital of Verona|
|Study Chair:||Maddalena Trombetta, Asst Prof||Division of Endocrinology and Metabolic Diseases, University Hospital of Verona|