Efficacy of Ursodeoxycholic Acid (UDCA) in Patients With Type 2 Diabetes

NCT05416580 | Unknown Phase 3

• 1 other identifier: UDCA01T2DM
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of ursodeoxycholic acid (UDCA) compared to placebo on biomarkers of oxidative stress, inflammation, and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM) who are treated with metformin but did not meet the target HbA1C \< 7%.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Type 2; UDCA; Metformin

Outcome Measures

Primary Outcomes (7)

• Change in oxidative stress biomarkers levels: superoxide dismutase (SOD), catalase, and malondialdehyde (MDA)

  ELISA assay (same units)

  From Baseline and after 8 weeks

• Change in pro-inflammatory markers concentrations: tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)

  ELISA assay (same units)

  From Baseline and after 8 weeks

• Change in serum levels of homocystein

  Detection by fluorescence polarization immunoassay

  From Baseline and after 8 weeks

• Change in serum levels of von Willebrand factor (vWF), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Adhesion Molecule 1 (VCAM-1), and fibrinogen

  ELISA assay (same units)

  From Baseline and after 8 weeks

• Change in serum levels of Vitamin D and Folic acid

  Microparticle enzyme immunoassay (same units)

  From Baseline and after 8 weeks

• Change in Total antioxidant capacity (TAC) level

  Results expressed in units μg/ml Trolox equivalents

  From Baseline and after 8 weeks

• Change in inflammation marker level: high sensitivity CRP

  Turbid metric test

  From Baseline and after 8 weeks

Secondary Outcomes (3)

• Change in Haemoglobin A1C (HbA1C)

  From Baseline and after 8 weeks

• Change in Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides

  From Baseline and after 8 weeks

• Change in body weight

  From Baseline and after 8 weeks

Study Arms (2)

UDCA + metformin

EXPERIMENTAL

UDCA in addition to Metformin Treatment All subjects will be treated with UDCA 1500 mg/day, and Metformin, up to 2000 mg/day, by oral administration, respectively, for 8 weeks.

Drug: UDCA (Ursodeoxycholic acid); Drug: Metformin

Placebo + metformin

PLACEBO COMPARATOR

Placebo of UDCA in addition to Metformin Treatment All subjects will be treated with a Placebo of UDCA, and Metformin, up to 2000 mg/day, by oral administration, respectively, for 8 weeks.

Drug: Placebo; Drug: Metformin

Interventions

UDCA (Ursodeoxycholic acid) DRUG

UDCA is administered orally in addition to metformin therapy in the recommended doses in patients with type 2 diabetes mellitus.

Also known as: Ursofalk, Bilexin

UDCA + metformin

Placebo DRUG

Placebo is administered orally in addition to metformin therapy in the recommended doses in patients with type 2 diabetes mellitus.

Placebo + metformin

Metformin DRUG

Metformin therapy is administered in the recommended dose in patients with type 2 diabetes mellitus.

Also known as: Siofor, Glucophage

Placebo + metformin; UDCA + metformin

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Type 2 Diabetes mellitus verified at least 1 year prior to the study enrollment
• Treatment with metformin at a maximally tolerated dose (up to 2000 mg/day) in patients with an incomplete biochemical response showing HbA1c ≥ 6,5%.
• Body mass index (BMI) corresponding to overweight and obesity (≥ 25 kg/m2)

You may not qualify if:

• Insulin treatment within 12 weeks prior to the study enrollment
• Treatment with Glucagon-like peptide 1 (GLP-1) analogs within 12 weeks prior to the study enrollment
• Systemic administration of glucocorticoids continuously for 10 days within 12 weeks prior to the study enrollment
• Prior and concomitant immunosuppressants treatment (other than glucocorticoids)
• History and current serious psychiatric disorders that could affect treatment adherence
• Co-existing uncontrolled cardiovascular disease (i.e arterial hypertension), respiratory insufficiency, acute or chronic renal failure (creatinine clearance \< 60 ml/min), and liver diseases such as acute or chronic viral hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, non-alcoholic fatty liver disease, hemochromatosis, and liver failure.
• Known history of cholecystitis
• Pregnant or lactating women
• Known hypersensitivity to UDCA, or other bile acids
• History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening)
• Participation in any other interventional study

Sponsors & Collaborators

• University of Banja Luka: lead

Study Sites (1)

Public Health Institution Dom zdravlja Banja Luka

Banja Luka, Republika Srpska, 78000, Bosnia and Herzegovina

Location

Related Publications (1)

• Lakic B, Skrbic R, Uletilovic S, Mandic-Kovacevic N, Grabez M, Saric MP, Stojiljkovic MP, Soldatovic I, Janjetovic Z, Stokanovic A, Stojakovic N, Mikov M. Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, Placebo-Controlled Clinical Study. J Diabetes Res. 2024 Feb 29;2024:4187796. doi: 10.1155/2024/4187796. eCollection 2024.

  PMID: 38455850 DERIVED

Related Links

• Bile acids signaling pathways have become attractive targets for the treatment of various metabolic diseases and metabolic syndrome opening the new potential avenue in their treatment.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Ursodeoxycholic Acid; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Ranko Skrbic, Professor

  University of Banja Luka

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: June 13, 2022
• Study Start: September 12, 2022
• Primary Completion: March 1, 2024
• Study Completion: April 1, 2024
• Last Updated: May 11, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1)