Clinical trial NCT06021119: Feasibility of DPP-4 Inhibitor Therapy on Advanced Hybrid Closed Loop System
Official title: Feasibility of DPP-4 Inhibitor for the Treatment of Iftar-Related Glycemic Excursions in Patients With Type 1 Diabetes on MiniMed™ 780G Advanced Hybrid Closed Loop System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Time in Range
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-09-01
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Maximum age (years): 27
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Ramadan Iftar meal typically causes glucose excursions. Dipeptidyl peptidase-4 inhibitors increase serum concentrations of glucagon-like peptide-1 and thus, decrease blood glucose levels with low risk of hypoglycemia.

Aim: To investigate the efficacy and safety of vildagliptin as an add-on therapy among adolescents and young adults with type 1 diabetes mellitus (T1DM) on glucose excursions of Iftar Ramadan meals and glycemic metrics during advanced hybrid closed-loop (AHCL) treatment.

Detailed description: Current management of people with type 1 diabetes mellitus (T1DM) on intensive insulin therapy recognizes carbohydrates as the most important determinant of postprandial glycaemia; hence, worldwide guidelines recommend carbohydrates counting for determining pre-prandial insulin doses. Currently, the insulin to carbohydrate ratio (ICR) is frequently used to calculate the meal insulin dose. However, ICRs are considered difficult, ineffective and inaccurate for some patient, with an estimation error of around 20% in adults demonstrating only modest improvements in glycated hemoglobin (HbA1c). This lack of effectiveness and the wide variability using ICRs suggests it should be improved upon.

However, there have been only a few randomized control studies that investigated the efficacy and safety of DPP-4 inhibitors as an add-on drug in patients treated with basal insulin. Therefore, we conducted a one-month randomized control trial to investigate the efficacy and safety of DPP-4 inhibitors as an add-on therapy among adolescents and young adults with T1DM on glucose excursions of Iftar Ramadan meals and glucometrics during AHCL treatment .

Eligibility criteria: Inclusion Criteria:

* patients with type 1 diabetes (T1DM )for at least one year
* patients aged 12-27 years
* patients using MiniMed 780G AHCL system (Medtronic, Northridge, CA, USA) at least 6 months before the study
* patients with minimum daily insulin requirement of more than 8 units
* patients willingness and ability to adhere to the study protocol, access to the internet and a computer system that met requirements for uploading the study pump data.

Exclusion Criteria:

* patients with any microvascular or macrovascular complications
* pregnancy, lactation
* patients who had a point-of-care screening HbA1c \>10.0% (86 mmol/mol)
* patients with hypoglycemic unawareness or recurrent severe hypoglycemic episode in the last 6 months prior to recruitment
* patients with recurrent DKA (more than 2 episodes in the previous 6 months).
* patients with any chronic medical condition, current use of medications (other than insulin) that are known to affect blood glucose level.
* patients who had prior adverse reactions to the adjunctive agent

Primary outcomes:
measure: peak postprandial plasma glucose (PPG) level in mg/dl
timeFrame: 4 weeks
Secondary outcomes:
measure: Time in range %
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Nancy Elbarbary
Study officials:
References:
citation: Dyson PA, Twenefour D, Breen C, Duncan A, Elvin E, Goff L, Hill A, Kalsi P, Marsland N, McArdle P, Mellor D, Oliver L, Watson K. Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes. Diabet Med. 2018 May;35(5):541-547. doi: 10.1111/dme.13603.
citation: Brazeau AS, Mircescu H, Desjardins K, Leroux C, Strychar I, Ekoe JM, Rabasa-Lhoret R. Carbohydrate counting accuracy and blood glucose variability in adults with type 1 diabetes. Diabetes Res Clin Pract. 2013 Jan;99(1):19-23. doi: 10.1016/j.diabres.2012.10.024. Epub 2012 Nov 10.
citation: Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 10.1056/NEJMoa1907863. Epub 2019 Oct 16.
citation: Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes. N Engl J Med. 2023 Mar 16;388(11):991-1001. doi: 10.1056/NEJMoa2210834.
citation: Lakshman R, Boughton C, Hovorka R. The changing landscape of automated insulin delivery in the management of type 1 diabetes. Endocr Connect. 2023 Jul 31;12(8):e230132. doi: 10.1530/EC-23-0132.