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

November 2, 2023 updated by: Nancy Samir Elbarbary, Ain Shams University

The Impact of Sitagliptin as an Add on Therapy With Closed Loop Control in Adolescents With Type 1 Diabetes Mellitus and Diabetic Nephropathy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Evidence from preclinical investigation suggests that DPP-4 inhibition may have beneficial effects on various metabolic indicators in diabetes. DPP-4 inhibitors, such as sitagliptin, have been widely used as outstanding blood glucose-dependent antidiabetic agents for patients with type 2 diabetes(T2DM). DPP-4 inhibitors have a lowering effect on the glycemic level and were not associated with increasing incidence of adverse events. The reno-protective effects of DPP-4 inhibition in diabetic nephropathy could be a consequence of the antidiabetic actions of DPP-4 inhibitors.

A second-generation advanced hybrid closed loop ( AHCL) system has been developed to further improve glycemic control and usability, with adjustable target glucose and automated correction boluses. This system provides proportional integral derivate (PID) algorithm with insulin feedback with adaptive insulin limits and model based auto-corrections located on the pump. Sitagliptin demonstrated an overall decrease in blood glucose concentrations in adults with T1DM when used as an adjunct therapy with an insulin only closed loop (CL) system.

Stromal cell-derived factor-1 (SDF-1) is ubiquitously expressed in diverse organs and has multiple functions. SDF-1 is cleaved and inactivated by the DPP-4 enzyme. The DPP-4 enzyme is highly expressed in the kidney. It has been suggested that renal SDF-1 upregulation by DPP-4 inhibition produces multiple protective actions on the diabetic kidney.

In view of these data, the investigators assessed the impact of sitagliptin as add on therapy with closed loop control in adolescents with T1DM on glycemic control, diabetic nephropathy and SDF-1 as a marker for nephropathy.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11361
        • Nancy Elbarbary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Oral sitagliptin 50 mg supplementation for three months
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
oral sitagliptin supplementation for three months
No Intervention: Control group ( No intake of oral sitagliptin 50 mg supplementation for three months)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Time in range
Time Frame: 3 months
Change in Time in range (TIR) in intervention group in comparison to control group
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of microalbuminuria
Time Frame: 3 months
Change in microalbuminuria level in intervention group in comparison to control group
3 months
Level of Stromal cell-derived factor-1 (SDF-1)
Time Frame: 3 months
Change in Stromal cell-derived factor-1 (SDF-1)in intervention group in comparison to control group
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Collaborators

Ahram Canadian University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2022

Primary Completion (Actual)

June 1, 2023

Study Completion (Actual)

June 15, 2023

Study Registration Dates

First Submitted

October 30, 2023

First Submitted That Met QC Criteria

October 30, 2023

First Posted (Actual)

November 3, 2023

Study Record Updates

Last Update Posted (Actual)

November 7, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ain Shams University202388

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

All data are available upon request

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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