Effect of Dipeptidyl Peptidase- 4 Inhibitors on Non-Alcoholic Steatohepatitis and Type 1 Diabetes

NCT06348706 | Completed Phase 3

• 1 other identifier: Ain Shams University25032024
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD) that can precipitate to advanced fibrosis and leads to cardiovascular morbidity and mortality. Many patients with type 1 diabetes mellitus (T1DM) had histological evidence of steatosis and met the histological criteria for NASH. Matrix metalloproteinase-14 (MMP-14) is a type 1 transmembrane proteinase expressed in liver fibrosis and is involved in the development of atherosclerosis and cardiovascular disease. Hepatic dipeptidyl peptidase-4 (DPP-4) expression in NAFLD may be directly associated with hepatic lipogenesis and liver injury. Some studies showed the beneficial effect of dipeptidyl peptidase-4 (DDP-4) inhibitors in NAFLD/NASH for their role in improving hepatic glucose metabolism. Vildagliptin, a DPP-4 inhibitor, could be promising therapeutic agents for NAFLD/NASH. To the best of our knowledge, no previous study assessed the role of DPP-4 inhibitors in adolescent patients with T1DM and NASH. Objectives: This randomized-controlled clinical trial assessed the impact of the oral DPP-4 inhibitor, vildagliptin, as an add-on therapy on NASH in adolescents with T1DM as well as its effect on glycemic control, lipid profile, MMP-14 levels and CIMT as a marker for subclinical atherosclerosis. Methods: This study included 60 adolescents with T1DM and NASH with a mean age 15.6 ± 2.08 years and disease duration ≥ 5 years. Forty age- and sex-matched healthy subjects with a mean age 14.9 ± 3.2 years were enrolled as healthy controls to compare MMP-14 levels. T1DM patients were randomly assigned to receive oral vildagliptin (50 mg daily) with lunch meal for six months or not. Fasting and 2 hours post-prandial blood glucose levels, HbA1c, liver function tests, fasting lipid profile, hepatic steatosis index and triglyceride glucose (TyG) index were assessed. MMP-14 levels were measured by enzyme-linked immunosorbent assay among all patients and healthy controls. CIMT was assessed using Doppler ultrasound and transient elastography with controlled attenuation parameter (CAP) was performed to assess liver stiffness and steatosis stage.

Conditions

Diabetes Mellitus, Type 1; NASH

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related effect on NASH status in adolescents with type 1 diabetes mellitus

  Effect of DPP-4 inhibitors on NASH in adolescents with type 1 diabetes mellitus measured by Doppler ultrasound and transient elastography with controlled attenuation parameter (CAP) to assess liver stiffness and steatosis stage.

  6 months

Secondary Outcomes (2)

• Number of participants with treatment-related Matrix metalloproteinase-14 (MMP-14) level change

  6 months

• Number of participants with treatment-related Glycemic control (HbA1c%) level change

  6 months

Study Arms (2)

Dipeptidyl peptidase-4 inhibitors supplementation

ACTIVE COMPARATOR

Intervention group receiving Dipeptidyl peptidase-4 inhibitors supplementation

Drug: Dipeptidyl peptidase 4 (DPP-4) inhibitor

Control group

NO INTERVENTION

Control group not receiving Dipeptidyl peptidase-4 inhibitors supplementation

Interventions

Dipeptidyl peptidase 4 (DPP-4) inhibitor DRUG

Intervention group received Dipeptidyl peptidase-4 (DPP-4) inhibitors supplementation in a dose of 50 mg with main meal for 6 months.

Also known as: Dipeptidyl peptidase-4 inhibitors

Dipeptidyl peptidase-4 inhibitors supplementation

Eligibility Criteria

• Age: 12 Years - 18 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adolescents diagnosed with type 1 diabetes according to ISPAD guidelines .
• Patients aged 12-18 years with NASH.
• Patients on regular visit to clinic.
• Patients on regular insulin therapy.

You may not qualify if:

• Patients with renal impairment due to cause other than diabetes.
• Patients with hypertension.
• Hyper- or hypo-thyroidism.
• Hepatitis virus infection (B or C) or any evidence of infection.
• History of liver disease other than NASH such as cholestasis and Wilson disease.
• Patients with autoimmune hepatitis.
• Recurrent diabetic ketoacidosis (more than 2 episodes in the previous 12 months)
• Patients were already on anti-hypertensive drugs or any antioxidant therapy such as vitamin supplements.
• Taking any vitamins or food supplements one month before study.
• Participation in a previous investigational drug study within 3 months preceding screening.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Nancy Elbarbary

Cairo, 11361, Egypt

Location

Related Publications (7)

• Temple JL, Cordero P, Li J, Nguyen V, Oben JA. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence. Int J Mol Sci. 2016 Jun 15;17(6):947. doi: 10.3390/ijms17060947.

  PMID: 27314342 RESULT

• Verges B. Cardiovascular disease in type 1 diabetes: A review of epidemiological data and underlying mechanisms. Diabetes Metab. 2020 Nov;46(6):442-449. doi: 10.1016/j.diabet.2020.09.001. Epub 2020 Sep 28.

  PMID: 32998054 RESULT

• Geervliet E, Moreno S, Baiamonte L, Booijink R, Boye S, Wang P, Voit B, Lederer A, Appelhans D, Bansal R. Matrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis. J Control Release. 2021 Apr 10;332:594-607. doi: 10.1016/j.jconrel.2021.03.016. Epub 2021 Mar 15.

  PMID: 33737203 RESULT

• Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Zenari L, Cigolini M, Falezza G, Arcaro G. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care. 2006 Jun;29(6):1325-30. doi: 10.2337/dc06-0135.

  PMID: 16732016 RESULT

• Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Jsg-Nafld JSGON. Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. Int J Mol Sci. 2020 Mar 11;21(6):1907. doi: 10.3390/ijms21061907.

  PMID: 32168769 RESULT

• Wang Q, Long M, Qu H, Shen R, Zhang R, Xu J, Xiong X, Wang H, Zheng H. DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Diabetes Res. 2018 Jan 8;2018:5308582. doi: 10.1155/2018/5308582. eCollection 2018.

  PMID: 29507862 RESULT

• Hussain M, Majeed Babar MZ, Hussain MS, Akhtar L. Vildagliptin ameliorates biochemical, metabolic and fatty changes associated with non alcoholic fatty liver disease. Pak J Med Sci. 2016 Nov-Dec;32(6):1396-1401. doi: 10.12669/pjms.326.11133.

  PMID: 28083033 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Exopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Design

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

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 5, 2024
• Study Start: November 10, 2022
• Primary Completion: December 1, 2023
• Study Completion: January 15, 2024
• Last Updated: April 5, 2024

Record last verified: 2024-03

Locations

EG (1)