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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
Sponsor:
Collaborators:
Universita di Verona
European Foundation for the Study of Diabetes
Information provided by (Responsible Party):
Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Metabolic tests:

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.

Metabolic tests:

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.





Primary Outcome Measures :
  1. 1. Composite plasma glucose and hormone responses to a mixed meal; 2. Glucose control coefficients [ Time Frame: 24 months ]
    1. Timed curves of composite plasma glucose, meal-derived glucose, endogenous glucose, insulin, glucagon and incretin hormone concentrations in response to a mixed meal.
    2. Composite glucose control coefficients (CCs) of each component of the glucose-insulin system at each time point of the mixed meal.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • patient must be aged between 18 (inclusive) and 65 years old;
  • patient must have been diagnosed with type 1 diabetes(positive islet cell antibodies;
  • use of an insulin pump to treat his/her diabetes for at least 1 year;
  • actively using a carbohydrate/insulin ratio for insulin bolus adjustments in order to keep blood glucose in a predefined range;
  • patient HbA1c is between 6,0% and 9,0% (standardized with DCCT);
  • patient must be willing to avoid consumption of acetaminophen containing products during the study involving DexCom (one CGM system which will be employed in this study) use;
  • patient must demonstrate proper mental status and cognition for the study;
  • patient has signed informed consent from prior to study entry.

Exclusion Criteria:

  • diabetic ketoacidosis within the 6 months prior to enrollment;
  • severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment;
  • pregnancy and breast feeding;
  • uncontrolled microvascular (diabetic)complications (other than diabetic non-proliferative retinopathy)such as history of laser coagulation, proliferative diabetic retinopathy, known diabetic nephropathy (other than microalbuminuria with normal creatinine) or neuropathy requiring treatment;
  • uncontrolled arterial hypertension (diastolic blood pressure >90 mmHg and/or systolic blood pressure >160 mmHg);
  • conditions which may increase the risk of hypoglycemia such as uncontrolled coronary artery disease during the previous year (e.g. history of myocardial infarction, acute coronary syndrome, therapeutic coronary intervention, coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, or positive stress test or catheterization with coronary blockages >50%), congestive heart failure, history of cerebrovascular event, seizure disorder, syncope, adrenal insufficiency, neurologic disease or atrial fibrillation;
  • drugs affecting glucose metabolism (oral steroids, thiazide diuretic, beta-blockers,beta-agonist, nicotinic acid, immunosuppressant agents, antiretroviral drugs and antipsychotics);
  • impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase > three times the upper reference limit;
  • impaired renal function measured as creatinine >1.2 times above the upper limit of normal; anticoagulant therapy other than aspirin;
  • known current or recent alcohol or drug abuse;
  • psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment);
  • mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

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): NCT02003274


Locations
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Italy
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
Sponsors and Collaborators
Azienda Ospedaliera Universitaria Integrata Verona
Universita di Verona
European Foundation for the Study of Diabetes
Investigators
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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

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

Publications:

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Responsible Party: Azienda Ospedaliera Universitaria Integrata Verona
ClinicalTrials.gov Identifier: NCT02003274     History of Changes
Other Study ID Numbers: Verona Artificial Pancreas
First Posted: December 6, 2013    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: March 2017
Keywords provided by Azienda Ospedaliera Universitaria Integrata Verona:
Mixed Meal Test
Insulin Pump
Continuous Glucose Monitoring
Metabolic Control Analysis
Closed Loop Control
Artificial Pancreas
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs