The Impact of Sitagliptin as an Add on Therapy With Closed Loop Control in Adolescents With Diabetic Nephropathy

NCT06115460 | Completed Phase 3 DMC

• 1 other identifier: Ain Shams University202388
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic nephropathy (DN) is one of the most frequent microvascular complications of diabetes mellitus, affecting 25 to 40% of patients with type 1 diabetes (T1DM). Early diagnosis, appropriate patient follow-up and treatment are essential to improve the outcomes. There is a need for improvements in insulin therapy for people with T1DM as the majority of patients are struggling to achieve glycemic targets. Technological advancements and oral adjuncts to insulin therapies are starting to be licensed for the use of people with T1DM. Dipeptidyl peptidase-4 (DPP-4), a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated β-cell destruction. DPP-4 degrades the peptide hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP). Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology.

Conditions

Type 1 Diabetic Nephropathy

Keywords

Type 1 diabetes; Diabetic nephropathy; Sitagliptin; Time in Range; Advanced hybrid closed system; Stromal cell-derived factor-1 (SDF-1)

Outcome Measures

Primary Outcomes (1)

• Percentage of Time in range

  Change in Time in range (TIR) in intervention group in comparison to control group

  3 months

Secondary Outcomes (2)

• Level of microalbuminuria

  3 months

• Level of Stromal cell-derived factor-1 (SDF-1)

  3 months

Study Arms (2)

Oral sitagliptin 50 mg supplementation for three months

ACTIVE COMPARATOR

Intervention group includes: adolescents with diabetic nephropathy on advanced hybrid closed loop system receiving oral sitagliptin 50 mg for three months on a daily basis

Drug: oral sitagliptin supplementation

Control group ( No intake of oral sitagliptin 50 mg supplementation for three months)

NO INTERVENTION

Control group includes: adolescents with diabetic nephropathy on advanced hybrid closed loop system who did not take oral sitagliptin 50 mg for three months on a daily basis

Interventions

oral sitagliptin supplementation DRUG

oral sitagliptin supplementation for three months

Oral sitagliptin 50 mg supplementation for three months

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• T1DM patients aged 12-18 years with at least 5 years disease duration defined according to the criteria of International Society for Pediatric and Adolescent Diabetes (ISPAD) .
• Patients on insulin pump therapy using Medtronic advanced hybrid closed system (Medtronic, Northridge, USA) with Guardian™ 3 sensor or Guardian™ 4 sensor and Guardian link transmitter initiated at least 6 months before the study, patients with minimum daily insulin requirement of more than 8 units, willingness and ability to adhere to the study protocol, and access to the internet as well as a computer system that met requirements for uploading the study pump data.
• Active diabetic nephropathy in the form of microalbuminuria (urinary albumin excretion ) 30-299 mg/g creatinine in two of three samples over a 3- to 6-months period despite angiotensin converting enzyme inhibitors).
• Hemoglobin A1c (HbA1c) ≤8.5%.
• Patients on regular visits to clinic.

You may not qualify if:

• patients with other diabetic microvascular complications (neuropathy or retinopathy) or with macrovascular complications.
• Patients with history of liver disease or any disorder likely to impair liver functions or elevated liver enzymes.
• Patients with any evidence of renal impairment due to causes other than diabetes.
• Patients with hypertension.
• Hepatitis virus infection (B or C) or any evidence of infection
• Participation in a previous investigational drug study within 3 months preceding screening.
• Hypoglycemic unawareness or recurrent severe hypoglycemic episodes in the last 6 months prior to recruitment.
• Recurrent diabetic ketoacidosis (DKA) (more than 2 episodes in the previous 6 months).
• Taking other oral hypoglycemic medications which could affect blood glucose.
• Patients with known allergy to sitagliptin.

Sponsors & Collaborators

• Ain Shams University: lead
• Ahram Canadian University: collaborator

Study Sites (1)

Nancy Elbarbary

Cairo, 11361, Egypt

Location

Related Publications (7)

• Zhong J, Rajagopalan S. Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease. Front Immunol. 2015 Sep 25;6:477. doi: 10.3389/fimmu.2015.00477. eCollection 2015.

  PMID: 26441982 BACKGROUND

• Weisman A, Bai JW, Cardinez M, Kramer CK, Perkins BA. Effect of artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a systematic review and meta-analysis of outpatient randomised controlled trials. Lancet Diabetes Endocrinol. 2017 Jul;5(7):501-512. doi: 10.1016/S2213-8587(17)30167-5. Epub 2017 May 19.

  PMID: 28533136 BACKGROUND

• Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010 Apr 22;10:7. doi: 10.1186/1472-6823-10-7.

  PMID: 20412573 BACKGROUND

• 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.

  PMID: 28134564 BACKGROUND

• Bergenstal RM, Nimri R, Beck RW, Criego A, Laffel L, Schatz D, Battelino T, Danne T, Weinzimer SA, Sibayan J, Johnson ML, Bailey RJ, Calhoun P, Carlson A, Isganaitis E, Bello R, Albanese-O'Neill A, Dovc K, Biester T, Weyman K, Hood K, Phillip M; FLAIR Study Group. A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial. Lancet. 2021 Jan 16;397(10270):208-219. doi: 10.1016/S0140-6736(20)32514-9.

  PMID: 33453783 BACKGROUND

• Ho TK, Shiwen X, Abraham D, Tsui J, Baker D. Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia. Cardiol Res Pract. 2012;2012:143209. doi: 10.1155/2012/143209. Epub 2012 Feb 22.

  PMID: 22462026 BACKGROUND

• Elbarbary NS, Ismail EA, El-Hamamsy MH, Ibrahim MZ, Elkholy AA. The DPP-4 inhibitor sitagliptin improves glycaemic control and early-stage diabetic nephropathy in adolescents with type 1 diabetes using the MiniMed 780G advanced hybrid closed-loop system: a randomised controlled trial. Diabetologia. 2024 Dec;67(12):2637-2649. doi: 10.1007/s00125-024-06265-7. Epub 2024 Sep 14.

  PMID: 39271520 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. of Pediatrics

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: November 3, 2023
• Study Start: March 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 15, 2023
• Last Updated: November 7, 2023

Record last verified: 2023-11

Locations

EG (1)