Ursodeoxycholic Acid as add-on Therapy in Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Clinical Study Evaluating the Use od Ursodeoxycholic Acid as Adjuvant Therapy in Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05902468
• Other study ID #: 4/2023 INTM
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 28, 2023
• Est. completion date: November 28, 2024

Study information

• Verified date: June 2023
• Source: Tanta University
• Contact: Eman Ghonaim, Assistant lecturer
• Phone: +20-010-970-821-57
• Email: eman.ghonim[@]pharm.tanta.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetes mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It is one of the most prevalent metabolic disorders globally. Despite the advancement in anti-diabetic drug therapy, most patients fail to achieve optimal glycemic control. therefore, there is a large unmet need to develop new strategies to improve the therapeutic outcomes in diabetic patients. This study is designed to evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in patients with type 2 diabetes mellitus.

Description:

Diabetes mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It is one of the most prevalent metabolic disorders globally. More than 75% of diabetic patients live in low- and middle-income countries. About 90% of diabetic patients have type 2 diabetes.

Insulin resistance (IR) and β-cell dysfunction are the two main pathophysiological events contributing to type 2 diabetes.

Insulin resistance is a pathological condition in which insulin-dependent tissues fail to properly respond to normal circulatory levels of insulin. Inflammatory mediators play a key role in insulin resistance. For example, tumor necrosis factor alpha (TNF-α) impairs insulin signaling via serine phosphorylation of insulin receptor substrate (IRS-1). Additionally, it reduces glucose transporter-4 (GLUT-4) expression, limiting glucose entry into adipocytes and skeletal muscle cells. Similarly, IL-6 induces IRS degradation. Oxidative stress interferes with insulin signal transduction leading to IR. It activates several serine-threonine kinase pathways, which, in turn, phosphorylates IRS proteins leading to subsequent degradation.

β-cell dysfunction is associated with β-cell death. In an excessive nutritional state, as in obesity, hyperglycemia and hyperlipidemia are often present, favoring IR and chronic inflammation. Under these circumstances, β-cells are subject to toxic pressures including inflammation, endoplasmic reticulum stress, oxidative stress, as well as amyloid stress, that ultimately lead to loss of islet integrity.

Ursodeoxycholic acid (UDCA) is an endogenous hydrophilic bile acid normally present in human bile and traditionally used for the treatment of liver diseases. UDCA has direct antioxidant properties. It decreased glucose levels, alleviated hyperinsulinemia, and improved islet function in rats with liver fibrosis. Therefore, this study is designed to evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in patients with type 2 diabetes mellitus.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: November 28, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who have been diagnosed with type 2 diabetes mellitus within the previous 12 months.

• Glycated hemoglobin (HbA1c) between 7% and 9%.

• Body mass index = 25 kg/m2

Exclusion Criteria:

• Pregnant or nursing women.

• Type 1 diabetes mellitus.

• Liver disease (alanine aminotransferase > 3 upper normal limit).

• Kidney disease (estimated glomerular filtration rate < 60 ml/min/1.73 m2).

• Inflammatory bowel diseases

• History of allergy and/or adverse reactions to the drugs used in the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Ursodeoxycholic acid
ursodeoxycholic acid 500 mg orally twice daily for 12 weeks

Locations

Country	Name	City	State
Egypt	Faculty of Medicine, Menoufia University	Shibin Al Kawm	Menoufia
Egypt	Faculty of medicine, Tanta University	Tanta	El-Gharbia

Sponsors (2)

Lead Sponsor	Collaborator
Tanta University	Menoufia University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control	Fasting blood glucose, glycated hemoglobin	12 weeks
Secondary	Lipid profile	Total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol	12 weeks
Secondary	Insulin resistance	Fasting insulin, HOMA-IR	12 weeks
Secondary	Oxidative stress marker	Serum malondialdehyde	12 weeks
Secondary	Inflammation marker	Interleukin-6, high mobility group box-1	12 weeks
Secondary	Serum asprosin		12 weeks