Patient Empowerment Through Predictive Personalised Decision Support(PEPPER)-Validation Study.

NCT03849755 | Completed

• 2 other identifiers: 669/18/EC689810
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Patient Empowerment through Predictive PERsonalised Decision Support (PEPPER) is an European Union (EU) funded research project to develop a personalised clinical decision support system for Type 1 Diabetes Mellitus (T1DM) self-management. The tool provides insulin bolus dose advice, tailored to the needs of individuals. The system uses Case-Based Reasoning (CBR), an artificial intelligence methodology that adapts to new situations according to past experience. The PEPPER system also incorporates a safety module that promotes safety by providing glucose alarms, low-glucose insulin suspension, carbohydrate recommendations and fault detection. The principal research objective is to demonstrate safety, feasibility and usability of the PEPPER system compared to a standard bolus calculator.

Conditions

Diabetes Mellitus, Type 1

Keywords

bolus advisor

Outcome Measures

Primary Outcomes (1)

• Change in the percentage of time in glucose target range (glucose levels 3.9-10 mmol/l or 70 - 180 mg/dl)

  6 months

Secondary Outcomes (26)

• Change in glycosylated hemoglobin (HbA1c) value

  6 months

• Change in the number of episodes of post-prandial hypoglycaemia (glucose level below 3,9 mmol/L or 70 mg/dl) within 4 hours

  6 months

• Change in the number of episodes of post-prandial hypoglycaemia (glucose level below 3,9 mmol/L or 70 mg/dl) within 6 hours

  6 months

• Change in the percentage of time in hyperglycaemia (glucose level above 10 mmol/l or 180 mg/dl)

  6 months

• Change in the percentage of time in hypoglycaemia (glucose level below 3, 9 mmol/L or 70 mg/dl)

  6 months

Study Arms (2)

PEPPER/Control

OTHER

Group with intervention applied (PEPPER system) during the first three months and then, after wash -out period, swap to control group (using standard bolus calculator) for the next 3 months.

Device: PEPPER system

Control/PEPPER

OTHER

Group without intervention applied (using standard bolus calculator) during the first three months and then, after wash -out period, swap to intervention group (using PEPPER system) for the next 3 months.

Device: PEPPER system

Interventions

PEPPER system DEVICE

The PEPPER system offers insulin dosing advice that is highly adaptive to the insulin needs of individuals by using Case-Base Reasoning (CBR) approach.

Control/PEPPER; PEPPER/Control

Eligibility Criteria

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

You may qualify if:

• Adults ≥18years of age
• Diagnosis of T1DM for \> 1 year
• On MDI using a basal-bolus insulin regime or CSII (insulin pump) for at least 6 month
• Structured education done and good ability perform carbohydrates (CHO) counting
• HbA1c ≥ 48mmol/mol and ≤ 86mmol/mol
• Using insulin carbohydrates ratio (ICR) and insulin sensitivity factor (ISF) to calculate the mealtime bolus
• An understanding of and willingness to follow the protocol and sign the informed consent
• CBG measurements at least 2 times per day for calibration of the CGM

You may not qualify if:

• Severe episode of hypoglycaemia (requiring 3rd party assistance) in the 6 months prior to enrolment
• Diabetic ketoacidosis in the last 6 months prior to enrolment
• Impaired awareness of hypoglycaemia (based on Gold score)
• Pregnancy, breastfeeding or intention of becoming pregnant over time of study procedures
• Enrolled in other clinical trials
• Have active malignancy or under investigation for malignancy
• Suspected or diagnosed endocrinopathy like adrenal insufficiency, unstable thyroidopathy, endocrine tumour
• Gastroparesis
• Autonomic neuropathy
• Macrovascular complications (acute coronary syndrome, transient ischaemic attack, cerebrovascular event within the last 12 months prior to enrolment in the study)
• Visual impairment including unstable proliferative retinopathy
• Reduced manual dexterity
• Inpatient psychiatric treatment
• Abnormal renal function test results (calculated Glomerular Filtration Rate (GFR) \<40 mL/min/1.73m2)
• Liver cirrhosis

Sponsors & Collaborators

• Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta: lead
• Imperial College London: collaborator
• Oxford Brookes University: collaborator
• Universitat de Girona: collaborator
• Cellnovo Limited: collaborator
• Romsoft SRL: collaborator

Study Sites (1)

Institut d'Investigació Biomèdica de Girona (IDIBGI)

Girona, 17007, Spain

Location

Related Publications (20)

• Buckingham B, Wilson DM, Lecher T, Hanas R, Kaiserman K, Cameron F. Duration of nocturnal hypoglycemia before seizures. Diabetes Care. 2008 Nov;31(11):2110-2. doi: 10.2337/dc08-0863. Epub 2008 Aug 11.

  PMID: 18694975 BACKGROUND

• Perez-Gandia C, Facchinetti A, Sparacino G, Cobelli C, Gomez EJ, Rigla M, de Leiva A, Hernando ME. Artificial neural network algorithm for online glucose prediction from continuous glucose monitoring. Diabetes Technol Ther. 2010 Jan;12(1):81-8. doi: 10.1089/dia.2009.0076.

  PMID: 20082589 BACKGROUND

• 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.

  PMID: 8366922 BACKGROUND

• Dassau E, Cameron F, Lee H, Bequette BW, Zisser H, Jovanovic L, Chase HP, Wilson DM, Buckingham BA, Doyle FJ 3rd. Real-Time hypoglycemia prediction suite using continuous glucose monitoring: a safety net for the artificial pancreas. Diabetes Care. 2010 Jun;33(6):1249-54. doi: 10.2337/dc09-1487.

  PMID: 20508231 BACKGROUND

• FDA Advisory Panel Votes to Recommend Non-Adjunctive Use of Dexcom G5 Mobile CGM. Diabetes Technol Ther. 2016 Aug;18(8):512-6. doi: 10.1089/dia.2016.07252.mr. Epub 2016 Jul 29. No abstract available.

  PMID: 27472488 BACKGROUND

• Garg SK, Bookout TR, McFann KK, Kelly WC, Beatson C, Ellis SL, Gutin RS, Gottlieb PA. Improved glycemic control in intensively treated adult subjects with type 1 diabetes using insulin guidance software. Diabetes Technol Ther. 2008 Oct;10(5):369-75. doi: 10.1089/dia.2007.0303.

  PMID: 18715213 BACKGROUND

• National Clinical Guideline Centre (UK). Type 1 Diabetes in Adults: Diagnosis and Management. London: National Institute for Health and Care Excellence (NICE); 2015 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK315808/

  PMID: 26334079 BACKGROUND

• Herrero P, Calm R, Vehi J, Armengol J, Georgiou P, Oliver N, Tomazou C. Robust fault detection system for insulin pump therapy using continuous glucose monitoring. J Diabetes Sci Technol. 2012 Sep 1;6(5):1131-41. doi: 10.1177/193229681200600518.

  PMID: 23063040 BACKGROUND

• Herrero P, Pesl P, Reddy M, Oliver N, Georgiou P, Toumazou C. Advanced Insulin Bolus Advisor Based on Run-To-Run Control and Case-Based Reasoning. IEEE J Biomed Health Inform. 2015 May;19(3):1087-96. doi: 10.1109/JBHI.2014.2331896.

  PMID: 24956470 BACKGROUND

• Herrero P, Pesl P, Bondia J, Reddy M, Oliver N, Georgiou P, Toumazou C. Method for automatic adjustment of an insulin bolus calculator: in silico robustness evaluation under intra-day variability. Comput Methods Programs Biomed. 2015 Apr;119(1):1-8. doi: 10.1016/j.cmpb.2015.02.003. Epub 2015 Feb 16.

  PMID: 25733405 BACKGROUND

• Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Bode B, Beck RW, Xing D, Gilliam L, Hirsch I, Kollman C, Laffel L, Ruedy KJ, Tamborlane WV, Weinzimer S, Wolpert H. Sustained benefit of continuous glucose monitoring on A1C, glucose profiles, and hypoglycemia in adults with type 1 diabetes. Diabetes Care. 2009 Nov;32(11):2047-9. doi: 10.2337/dc09-0846. Epub 2009 Aug 12.

  PMID: 19675193 BACKGROUND

• Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Tamborlane WV, Beck RW, Bode BW, Buckingham B, Chase HP, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Hirsch IB, Huang ES, Kollman C, Kowalski AJ, Laffel L, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer S, Wilson DM, Wolpert H, Wysocki T, Xing D. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008 Oct 2;359(14):1464-76. doi: 10.1056/NEJMoa0805017. Epub 2008 Sep 8.

  PMID: 18779236 BACKGROUND

• Kovatchev BP, Breton M, Man CD, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J Diabetes Sci Technol. 2009 Jan;3(1):44-55. doi: 10.1177/193229680900300106.

  PMID: 19444330 BACKGROUND

• Lepore G, Dodesini AR, Nosari I, Scaranna C, Corsi A, Trevisan R. Bolus calculator improves long-term metabolic control and reduces glucose variability in pump-treated patients with Type 1 diabetes. Nutr Metab Cardiovasc Dis. 2012 Aug;22(8):e15-6. doi: 10.1016/j.numecd.2012.04.001. Epub 2012 Jun 4. No abstract available.

  PMID: 22673770 BACKGROUND

• Reddy M, Pesl P, Xenou M, Toumazou C, Johnston D, Georgiou P, Herrero P, Oliver N. Clinical Safety and Feasibility of the Advanced Bolus Calculator for Type 1 Diabetes Based on Case-Based Reasoning: A 6-Week Nonrandomized Single-Arm Pilot Study. Diabetes Technol Ther. 2016 Aug;18(8):487-93. doi: 10.1089/dia.2015.0413. Epub 2016 May 19.

  PMID: 27196358 BACKGROUND

• Reddy M, Rilstone S, Cooper P, Oliver NS. Type 1 diabetes in adults: supporting self management. BMJ. 2016 Mar 10;352:i998. doi: 10.1136/bmj.i998. No abstract available.

  PMID: 26965473 BACKGROUND

• Vaddiraju S, Burgess DJ, Tomazos I, Jain FC, Papadimitrakopoulos F. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol. 2010 Nov 1;4(6):1540-62. doi: 10.1177/193229681000400632.

  PMID: 21129353 BACKGROUND

• Sovik O, Thordarson H. Dead-in-bed syndrome in young diabetic patients. Diabetes Care. 1999 Mar;22 Suppl 2:B40-2.

  PMID: 10097898 BACKGROUND

• Zisser H, Robinson L, Bevier W, Dassau E, Ellingsen C, Doyle FJ, Jovanovic L. Bolus calculator: a review of four "smart" insulin pumps. Diabetes Technol Ther. 2008 Dec;10(6):441-4. doi: 10.1089/dia.2007.0284.

  PMID: 19049372 BACKGROUND

• Avari P, Leal Y, Herrero P, Wos M, Jugnee N, Arnoriaga-Rodriguez M, Thomas M, Liu C, Massana Q, Lopez B, Nita L, Martin C, Fernandez-Real JM, Oliver N, Fernandez-Balsells M, Reddy M. Safety and Feasibility of the PEPPER Adaptive Bolus Advisor and Safety System: A Randomized Control Study. Diabetes Technol Ther. 2021 Mar;23(3):175-186. doi: 10.1089/dia.2020.0301.

  PMID: 33048581 DERIVED

Related Links

• Project website

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

• José Manuel Fernández Real

  Institut d'Investigació Biomèdica de Girona (IDIBGI) Unitat de Diabetis, Endocrinologia i Nutrició de Girona (UDENG) Hospital Universitari de Girona Dr Josep Trueta

  PRINCIPAL INVESTIGATOR

• Mercè Fernández-Balsells

  Institut d'Investigació Biomèdica de Girona (IDIBGI) Unitat de Diabetis, Endocrinologia i Nutrició de Girona (UDENG) Hospital Universitari de Girona Dr Josep Trueta

  PRINCIPAL INVESTIGATOR

• Nick Oliver

  Imperial Collage London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: PEPPER study is a randomized cross-over clinical trial with 50 participants. After 4 weeks of ruin-in period all subjects will be randomized to either control group or intervention group in 1:1 ratio. The groups will be stratified by pump or MDI. After 3 months, each group will revert to their standard therapy for 4 weeks (wash-out period) and then crossover to the other group. All participants will be using CGM during whole study.

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: February 21, 2019
• Study Start: November 15, 2018
• Primary Completion: November 9, 2019
• Study Completion: November 9, 2019
• Last Updated: August 4, 2020

Record last verified: 2020-08

Locations

ES (1)