Effect of Automated Insulin Delivery on Early-stage Diabetic Complications (AID-Comp)
Primary Purpose
Type 1 Diabetes
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Medtronic MiniMed 780G with SmartGuard activation
Medtronic MiniMed 780G without SmartGuard activation
Sponsored by
About this trial
This is an interventional other trial for Type 1 Diabetes focused on measuring Automated insulin delivery, Type 1 Diabetes complications
Eligibility Criteria
Inclusion Criteria:
- Male and female patients
- T1D patients above 18 years in CSII treatment for at least 3 months
- HbA1c values between 6.0% and 9.5%
- Disease duration ≥ 2 years
- Written informed consent obtained from the patient
Exclusion Criteria:
- Pregnancy
- Participation to other clinical trials
- A history of alcohol or drug abuse
- Advanced diabetic nephropathy defined as presence of albuminuria ≥ 300 mg/g or eGFR < 60 ml/min/1,73m2
- Proliferative Diabetic retinopathy or macular edema
- Established Atherosclerotic Cardiovascular Disease (ASCVD) or history of heart failure
- Presence of serious diseases or conditions which in the opinion of the Investigator makes patient non-eligible for the study
- Hypoglycemia Unawareness (Clarke score > 4)
- Patients unable to understand spoken and written Italian language
Sites / Locations
- ASST FBF SaccoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Study Group A (Intervention)
Study Group B (Control)
Arm Description
Group treated with automated insulin delivery (advanced hybrid closed-loop)
Group treated with predictive low glucose suspend (sensor augmented pump - PLGS)
Outcomes
Primary Outcome Measures
Time in glycemic range 70-180 mg/dl
time spent by the patient in glucose range
Glycated Hemoglobin (HbA1c)
percentage of hemoglobin glycosylated
Secondary Outcome Measures
Early microangiopathic damage markers: sTNFR-1/2
sTNFR-1/2 (pg/ml)
Early microangiopathic damage markers: B-2 microglobulin
B-2 microglobulin (pg/ml)
Early microangiopathic damage markers: cystatin C
cystatin C (ng/ml)
Early microangiopathic damage markers: neutrophil gelatinase-associated lipocalin
neutrophil gelatinase-associated lipocalin (ng/ml)
Early microangiopathic damage markers: osteopontin
osteopontin (pg/ml)
Early microangiopathic damage markers: vWF levels
vWF levels (ng/ml)
Endothelial disfunction
Endothelial-dependent dilation (EDD) is considered a marker of dysfunctional abnormalities involved in early phases of atherosclerosis development. Changes in EDD precede structural changes and occurs in the preclinical phase of vascular disease.
In the present study endothelial dependent dilation is assessed by color Doppler evaluation of flow increase after hyperemia.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05477030
Brief Title
Effect of Automated Insulin Delivery on Early-stage Diabetic Complications
Acronym
AID-Comp
Official Title
Effect of Automated Insulin Delivery With Advanced Closed-loop on Glucose Outcomes and Early-stage Diabetic Complications
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2022 (Actual)
Primary Completion Date
January 31, 2023 (Anticipated)
Study Completion Date
February 23, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Milan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Aim of this study is to verify the effects of an advanced HCL (Medtronic Minimed™ 780G) compared to SAP with PLGS on metabolic outcomes and markers of early microvascular damage in a population of adults with T1D previously treated with CSII. Evaluation of endothelial disfunction and autonomic neuropathy will also be performed.
Detailed Description
New algorithms for the automation of insulin delivery (AID) are showing great benefit on glucose control in people with type 1 diabetes. Indeed, Hybrid closed loop (HCL) systems can improve HbA1c levels, percentage of time in defined glucose range, time below range and time over range, according to RCT and observational studies results. However, scientific evidences demonstrating potential benefits on the reduction of diabetes complications are limited regarding CSII or SAP with demonstrated reduction of cardiovascular mortality, improvement of albuminuria and peripheral nerve damage.
Data on AID effects on complications of diabetes are missing. In this study intermediate damage markers will be measured to assess potential effects of AID in comparison to sensor augmented pumps.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Automated insulin delivery, Type 1 Diabetes complications
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Open label randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Study Group A (Intervention)
Arm Type
Active Comparator
Arm Description
Group treated with automated insulin delivery (advanced hybrid closed-loop)
Arm Title
Study Group B (Control)
Arm Type
Active Comparator
Arm Description
Group treated with predictive low glucose suspend (sensor augmented pump - PLGS)
Intervention Type
Device
Intervention Name(s)
Medtronic MiniMed 780G with SmartGuard activation
Intervention Description
Insulin pump implemented with alghoritm for automatic modulation of insulin delivery (to increase time in glucose range 70-180 mg/dl)
Intervention Type
Device
Intervention Name(s)
Medtronic MiniMed 780G without SmartGuard activation
Intervention Description
Insulin pump implemented with alghoritm for low glucose insulin suspension (to reduce hypoglycemia rate)
Primary Outcome Measure Information:
Title
Time in glycemic range 70-180 mg/dl
Description
time spent by the patient in glucose range
Time Frame
From Baseline to 26 weeks
Title
Glycated Hemoglobin (HbA1c)
Description
percentage of hemoglobin glycosylated
Time Frame
From Baseline to 26 weeks
Secondary Outcome Measure Information:
Title
Early microangiopathic damage markers: sTNFR-1/2
Description
sTNFR-1/2 (pg/ml)
Time Frame
From Baseline to 26 weeks
Title
Early microangiopathic damage markers: B-2 microglobulin
Description
B-2 microglobulin (pg/ml)
Time Frame
From Baseline to 26 weeks
Title
Early microangiopathic damage markers: cystatin C
Description
cystatin C (ng/ml)
Time Frame
From Baseline to 26 weeks
Title
Early microangiopathic damage markers: neutrophil gelatinase-associated lipocalin
Description
neutrophil gelatinase-associated lipocalin (ng/ml)
Time Frame
From Baseline to 26 weeks
Title
Early microangiopathic damage markers: osteopontin
Description
osteopontin (pg/ml)
Time Frame
From Baseline to 26 weeks
Title
Early microangiopathic damage markers: vWF levels
Description
vWF levels (ng/ml)
Time Frame
From Baseline to 26 weeks
Title
Endothelial disfunction
Description
Endothelial-dependent dilation (EDD) is considered a marker of dysfunctional abnormalities involved in early phases of atherosclerosis development. Changes in EDD precede structural changes and occurs in the preclinical phase of vascular disease.
In the present study endothelial dependent dilation is assessed by color Doppler evaluation of flow increase after hyperemia.
Time Frame
From Baseline to 26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female patients
T1D patients above 18 years in CSII treatment for at least 3 months
HbA1c values between 6.0% and 9.5%
Disease duration ≥ 2 years
Written informed consent obtained from the patient
Exclusion Criteria:
Pregnancy
Participation to other clinical trials
A history of alcohol or drug abuse
Advanced diabetic nephropathy defined as presence of albuminuria ≥ 300 mg/g or eGFR < 60 ml/min/1,73m2
Proliferative Diabetic retinopathy or macular edema
Established Atherosclerotic Cardiovascular Disease (ASCVD) or history of heart failure
Presence of serious diseases or conditions which in the opinion of the Investigator makes patient non-eligible for the study
Hypoglycemia Unawareness (Clarke score > 4)
Patients unable to understand spoken and written Italian language
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elio Ippolito, MS
Phone
0239042648
Ext
+39
Email
elio.ippolito@unimi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Rossi, MD
Phone
0239044027
Ext
+39
Email
rossi.antonio@asst-fbf-sacco.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paolo Fiorina, MD, PhD
Organizational Affiliation
ASST-FBF-Sacco, University of Milan
Official's Role
Principal Investigator
Facility Information:
Facility Name
ASST FBF Sacco
City
Milan
ZIP/Postal Code
20157
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elio Ippolito, Dr.
Phone
02 39042648
Email
ippolito.elio@asst-fbf-sacco.it
First Name & Middle Initial & Last Name & Degree
Paolo Fiorina, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
8366922
Citation
Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
Results Reference
result
PubMed Identifier
12020338
Citation
Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002 May 15;287(19):2563-9. doi: 10.1001/jama.287.19.2563.
Results Reference
result
PubMed Identifier
16371630
Citation
Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22;353(25):2643-53. doi: 10.1056/NEJMoa052187.
Results Reference
result
PubMed Identifier
31548241
Citation
Pettus JH, Zhou FL, Shepherd L, Preblick R, Hunt PR, Paranjape S, Miller KM, Edelman SV. Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study. Diabetes Care. 2019 Dec;42(12):2220-2227. doi: 10.2337/dc19-0830. Epub 2019 Sep 23.
Results Reference
result
PubMed Identifier
18644063
Citation
Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med. 2008 Jul;25(7):765-74. doi: 10.1111/j.1464-5491.2008.02486.x.
Results Reference
result
PubMed Identifier
18761648
Citation
Pankowska E, Blazik M, Dziechciarz P, Szypowska A, Szajewska H. Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials. Pediatr Diabetes. 2009 Feb;10(1):52-8. doi: 10.1111/j.1399-5448.2008.00440.x. Epub 2008 Aug 27.
Results Reference
result
PubMed Identifier
18201210
Citation
EQuality1 Study Group--Evaluation of QUALITY of Life and Costs in Diabetes Type 1; Nicolucci A, Maione A, Franciosi M, Amoretti R, Busetto E, Capani F, Bruttomesso D, Di Bartolo P, Girelli A, Leonetti F, Morviducci L, Ponzi P, Vitacolonna E. Quality of life and treatment satisfaction in adults with Type 1 diabetes: a comparison between continuous subcutaneous insulin infusion and multiple daily injections. Diabet Med. 2008 Feb;25(2):213-20. doi: 10.1111/j.1464-5491.2007.02346.x. Epub 2008 Jan 14.
Results Reference
result
PubMed Identifier
15016198
Citation
Maniatis AK, Toig SR, Klingensmith GJ, Fay-Itzkowitz E, Chase HP. Life with continuous subcutaneous insulin infusion (CSII) therapy: child and parental perspectives and predictors of metabolic control. Pediatr Diabetes. 2001 Jun;2(2):51-7. doi: 10.1034/j.1399-5448.2001.002002051.x.
Results Reference
result
PubMed Identifier
21933908
Citation
Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Perkins BA, Welsh JB, Willi SM, Wood MA; STAR 3 Study Group. Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase. Diabetes Care. 2011 Nov;34(11):2403-5. doi: 10.2337/dc11-1248. Epub 2011 Sep 20.
Results Reference
result
PubMed Identifier
30089663
Citation
Forlenza GP, Li Z, Buckingham BA, Pinsker JE, Cengiz E, Wadwa RP, Ekhlaspour L, Church MM, Weinzimer SA, Jost E, Marcal T, Andre C, Carria L, Swanson V, Lum JW, Kollman C, Woodall W, Beck RW. Predictive Low-Glucose Suspend Reduces Hypoglycemia in Adults, Adolescents, and Children With Type 1 Diabetes in an At-Home Randomized Crossover Study: Results of the PROLOG Trial. Diabetes Care. 2018 Oct;41(10):2155-2161. doi: 10.2337/dc18-0771. Epub 2018 Aug 8.
Results Reference
result
PubMed Identifier
27629148
Citation
Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.
Results Reference
result
PubMed Identifier
25078901
Citation
Nimri R, Muller I, Atlas E, Miller S, Fogel A, Bratina N, Kordonouri O, Battelino T, Danne T, Phillip M. MD-Logic overnight control for 6 weeks of home use in patients with type 1 diabetes: randomized crossover trial. Diabetes Care. 2014 Nov;37(11):3025-32. doi: 10.2337/dc14-0835. Epub 2014 Jul 30.
Results Reference
result
PubMed Identifier
28134564
Citation
Garg SK, Weinzimer SA, Tamborlane WV, Buckingham BA, Bode BW, Bailey TS, Brazg RL, Ilany J, Slover RH, Anderson SM, Bergenstal RM, Grosman B, Roy A, Cordero TL, Shin J, Lee SW, Kaufman FR. Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes. Diabetes Technol Ther. 2017 Mar;19(3):155-163. doi: 10.1089/dia.2016.0421. Epub 2017 Jan 30.
Results Reference
result
PubMed Identifier
31166801
Citation
Salehi P, Roberts AJ, Kim GJ. Efficacy and Safety of Real-Life Usage of MiniMed 670G Automode in Children with Type 1 Diabetes Less than 7 Years Old. Diabetes Technol Ther. 2019 Aug;21(8):448-451. doi: 10.1089/dia.2019.0123. Epub 2019 Jun 5.
Results Reference
result
PubMed Identifier
31617752
Citation
Lepore G, Scaranna C, Corsi A, Dodesini AR, Trevisan R. Switching from Suspend-Before-Low Insulin Pump Technology to a Hybrid Closed-Loop System Improves Glucose Control and Reduces Glucose Variability: A Retrospective Observational Case-Control Study. Diabetes Technol Ther. 2020 Apr;22(4):321-325. doi: 10.1089/dia.2019.0302. Epub 2020 Feb 11.
Results Reference
result
PubMed Identifier
26100640
Citation
Steineck I, Cederholm J, Eliasson B, Rawshani A, Eeg-Olofsson K, Svensson AM, Zethelius B, Avdic T, Landin-Olsson M, Jendle J, Gudbjornsdottir S; Swedish National Diabetes Register. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study. BMJ. 2015 Jun 22;350:h3234. doi: 10.1136/bmj.h3234.
Results Reference
result
PubMed Identifier
26390102
Citation
Rosenlund S, Hansen TW, Rossing P, Andersen S. Effect of Sensor-Augmented Pump Treatment Versus Multiple Daily Injections on Albuminuria: A 1-Year Randomized Study. J Clin Endocrinol Metab. 2015 Nov;100(11):4181-8. doi: 10.1210/jc.2015-2839. Epub 2015 Sep 21.
Results Reference
result
PubMed Identifier
26331364
Citation
Rosenlund S, Hansen TW, Andersen S, Rossing P. Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections: a longitudinal follow-up study. Diabet Med. 2015 Nov;32(11):1445-52. doi: 10.1111/dme.12950. Epub 2015 Oct 6.
Results Reference
result
PubMed Identifier
27050468
Citation
Zabeen B, Craig ME, Virk SA, Pryke A, Chan AK, Cho YH, Benitez-Aguirre PZ, Hing S, Donaghue KC. Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality. PLoS One. 2016 Apr 6;11(4):e0153033. doi: 10.1371/journal.pone.0153033. eCollection 2016.
Results Reference
result
PubMed Identifier
31177185
Citation
Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, Murphy HR, Nimri R, Norgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028. Epub 2019 Jun 8.
Results Reference
result
PubMed Identifier
11246868
Citation
Fiorina P, La Rocca E, Venturini M, Minicucci F, Fermo I, Paroni R, D'Angelo A, Sblendido M, Di Carlo V, Cristallo M, Del Maschio A, Pozza G, Secchi A. Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes. Diabetes. 2001 Mar;50(3):496-501. doi: 10.2337/diabetes.50.3.496.
Results Reference
result
PubMed Identifier
30877659
Citation
Zoppini G, Bergamini C, Trombetta M, Sabbagh L, Dauriz M, Mantovani A, Targher G, Fossa I, Rinaldi E, Bonora E. Increased aortic stiffness index in patients with type 1 diabetes without cardiovascular disease compared to controls. J Endocrinol Invest. 2019 Sep;42(9):1109-1115. doi: 10.1007/s40618-019-01032-7. Epub 2019 Mar 16.
Results Reference
result
PubMed Identifier
7497862
Citation
Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995 Apr;18(4):517-22. doi: 10.2337/diacare.18.4.517.
Results Reference
result
PubMed Identifier
15735199
Citation
Polonsky WH, Fisher L, Earles J, Dudl RJ, Lees J, Mullan J, Jackson RA. Assessing psychosocial distress in diabetes: development of the diabetes distress scale. Diabetes Care. 2005 Mar;28(3):626-31. doi: 10.2337/diacare.28.3.626.
Results Reference
result
PubMed Identifier
9589237
Citation
Bott U, Muhlhauser I, Overmann H, Berger M. Validation of a diabetes-specific quality-of-life scale for patients with type 1 diabetes. Diabetes Care. 1998 May;21(5):757-69. doi: 10.2337/diacare.21.5.757.
Results Reference
result
Learn more about this trial
Effect of Automated Insulin Delivery on Early-stage Diabetic Complications
We'll reach out to this number within 24 hrs