Mixed Meal Test in Type 1 Diabetes: Optimization of Artificial Pancreas-Pilot Study

NCT01800734 | Unknown Phase 4

• 1 other identifier: RBonadonna artificial pancreas
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Physiology studies will be performed in patients with type 1 diabetes to define during a standardized mixed meal test: 1. The relationship between fast insulin analogue administration by i.v. infusion or by subcutaneous pumps and plasma insulin concentration and tissue insulin action; 2. The relationship between insulin action, glucose fluxes and glucose concentration, the latter one as measured in plasma or estimated by a s.c. glucose-sensor; 3. The concentration curves of some potential modifiers of the glucose-insulin system (i.e.: glucagon, incretin hormones, free fatty and amino acids). On the basis of these data, in silico phenocopies of the patients (virtual patients) will be created to measure the glucose control coefficients, which quantify the role played by each component of the glucose-insulin system on glucose concentration. One final purpose of this research is to develop and to optimize an algorithm able to integrate continuous glucose monitoring with continuous subcutaneous fast insulin analogue infusion, known as closed-loop control (CLC) or artificial pancreas.

Conditions

Diabetes Mellitus Type 1

Keywords

Mixed meal test; Insulin pump; Continuous glucose monitoring; Metabolic control analysis; Closed loop control; Artificial pancreas

Outcome Measures

Primary Outcomes (1)

• 1. Composite plasma glucose and hormone responses to a mixed meal 2. Glucose control coefficients

  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

  24 months

Secondary Outcomes (1)

• Composite plasma free fatty and amino acid responses to a mixed meal

  24 months

Study Arms (1)

Clamp-Mixed Meal Arm

OTHER

Twenty adults 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 Arm

Interventions

Clamp-Mixed Meal Arm OTHER

Standard clinical parameters will be assessed in all patients. Metabolic tests: A. Euglycemic insulin clamp. A standard euglycemic insulin clamp will be carried out 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.

Clamp-Mixed Meal Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead
• Universita di Verona: collaborator

Study Sites (1)

Division of Endocrinology and Metabolic Diseases - University Hospital of Verona-Piazzale Stefani 1

Verona, 37126, Italy

RECRUITING

Related Publications (2)

• Bonetti S, Trombetta M, Boselli ML, Turrini F, Malerba G, Trabetti E, Pignatti PF, Bonora E, Bonadonna RC. Variants of GCKR affect both beta-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2. Diabetes Care. 2011 May;34(5):1205-10. doi: 10.2337/dc10-2218. Epub 2011 Mar 16.

  PMID: 21411509 BACKGROUND

• Trombetta M, Boselli L, Cretti A, Cali A, Vettore M, Caruso B, Dorizzi R, Avogaro A, Muggeo M, Bonora E, Bonadonna RC. Type 2 diabetes mellitus: a disease of the governance of the glucose-insulin system: an experimental metabolic control analysis study. Nutr Metab Cardiovasc Dis. 2013 Jan;23(1):23-30. doi: 10.1016/j.numecd.2011.05.006. Epub 2011 Sep 19.

  PMID: 21937205 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Riccardo C Bonadonna, Assoc Prof

  Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

  PRINCIPAL INVESTIGATOR

• Enzo Bonora, Full Prof

  Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

  STUDY DIRECTOR

• Maddalena Trombetta, Asst Prof

  Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

  STUDY CHAIR

Central Study Contacts

Riccardo Bonadonna

CONTACT

045 8123115; riccardo.bonadonna@univr.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 28, 2013
• Study Start: October 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2015
• Last Updated: November 19, 2013

Record last verified: 2012-08

Locations

IT (1)