Clinical trial NCT05416580: Efficacy of Ursodeoxycholic Acid (UDCA) in Patients With Type 2 Diabetes
Official title: Randomized, Double-blind, Placebo-controlled Study of Ursodeoxycholic Acid (UDCA) Therapy on Biomarkers of Oxidative Stress, Inflammatory and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
UDCA
Metformin
Lead sponsor: University of Banja Luka
Sponsor class: OTHER
First posted: 2022-06-13
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%.

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled, evaluation of the efficacy of UDCA on oxidative stress, inflammation, and endothelial dysfunction in combination with metformin after 8 weeks in patients with T2DM who did not meet HbA1C \< 7%.

Study site: a single study center (Primary Health Care Institution in Banja Luka, as recruiter center) including Center for Biomedical Research, Faculty of Medicine University of Banja Luka, as reference coordinator and research center.

Sample size :

60 patients, randomized in a 1:1 allocation ratio.

Objectives

1. To investigate the effects of UDCA added to metformin on glycemia, HbA1C, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipoproteins, and body mass index.
2. To investigate whether UDCA has an impact on lipid peroxidation index, nitric oxide metabolites, hydrogen peroxide (H2O2), superoxide anion radical (O2-), and total antioxidant capacity.
3. To investigate whether UDCA has an impact on the dynamic of inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high sensitive CRP (hsCRP).
4. To investigate whether UDCA has an impact on von Willebrand factor (vWF), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Adhesion Molecule 1 (VCAM-1), fibrinogen, homocysteine, folic acid, and vitamin D levels.

Treatments arms:

UDCA (1500 mg/day) + Metformin (maximum tolerated daily dose) UDCA placebo + Metformin (maximum tolerated daily dose)

Treatment duration :

8 weeks

Assessment - clinical and laboratory sampling:

Informed consent and Screening - 7 days prior to randomization

Study visits (V):

V1 - Randomization and Enrollment (Baseline) V2 - 4 weeks after Baseline V3 - 8 weeks after Baseline.

No interim analysis is planned. The analysis will be performed at the end of the study after data review and freezing of the database according to the intent to treat principle.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in oxidative stress biomarkers levels: superoxide dismutase (SOD), catalase, and malondialdehyde (MDA)
timeFrame: From Baseline and after 8 weeks
measure: Change in pro-inflammatory markers concentrations: tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)
timeFrame: From Baseline and after 8 weeks
measure: Change in serum levels of homocystein
timeFrame: From Baseline and after 8 weeks
measure: Change in serum levels of von Willebrand factor (vWF), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Adhesion Molecule 1 (VCAM-1), and fibrinogen
timeFrame: From Baseline and after 8 weeks
measure: Change in serum levels of Vitamin D and Folic acid
timeFrame: From Baseline and after 8 weeks
measure: Change in Total antioxidant capacity (TAC) level
timeFrame: From Baseline and after 8 weeks
measure: Change in inflammation marker level: high sensitivity CRP
timeFrame: From Baseline and after 8 weeks
Secondary outcomes:
measure: Change in Haemoglobin A1C (HbA1C)
timeFrame: From Baseline and after 8 weeks
measure: Change in Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides
timeFrame: From Baseline and after 8 weeks
measure: Change in body weight
timeFrame: From Baseline and after 8 weeks
Other outcomes:
Locations:
city: Banja Luka
country: Bosnia and Herzegovina
facility: Public Health Institution Dom zdravlja Banja Luka
state: Republic Of Srpska
Study officials:
affiliation: University of Banja Luka
name: Ranko Skrbic, Professor
role: STUDY_CHAIR
References: