Effects of TUDCA on Endothelial Function in Type 2 DM

Study Overview
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Brief Summary
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The pilot study is designed to investigate the acute and chronic effects of the diet supplement tauroursodeoxycholic acid (TUDCA) on endothelial function in participants with type 2 diabetes mellitus.

Detailed Description
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This is a pilot study designed to investigate the effect of two doses of TUDCA on endothelial function.All subjects will receive 500 mg/day in a one week run-in period and then 1750 mg/day in one week treatment period. The study will consist of four visits (screening visit and three study visits), and last up to 2 weeks for individual subjects, depending on the time between visits. It is estimated that the study will last two years from IRB approval through data analysis.

Official Title
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Pilot Study of The Effects of Tauroursodeoxycholic Acid (TUDCA) on Endothelial Function in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2, Insulin Response, Endothelial Dysfunction

Intervention / Treatment
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* Dietary Supplement: Tauroursodeoxycholic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus defined as fasting glucose greater than or equal to 120 mg/dL, HgA1C ≥6.5% or ongoing treatment with hypoglycemic medication. Willing to give written informed consent and able to understand, to participate in and to comply with the study requirements. Exclusion Criteria: Women lactating or pregnant. All women with childbearing potential will undergo a urine pregnancy test at each visit to exclude pregnancy. Treatment with an investigational product within the last 30 days. Clinically evident major illness of other organ systems, including end-stage cancer, renal failure, or other conditions that in the opinion of the principal investigator make a clinical study inappropriate. Inability to provide informed consent. Clinical instability that would preclude withholding medications as determined by the study physician.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TUDCA Group<br>All subjects will receive 500 mg/day in a one week run-in period and then 1750 mg/day in one week treatment period of of the nutritional supplement Tauroursodeoxycholic acid (TUDCA). | Dietary Supplement: Tauroursodeoxycholic acid<br>* Tauroursodeoxycholic acid is an ambiphilic bile acid. It is the taurine conjugate form of ursodeoxycholic acid.<br>* Other names: TUDCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vascular function | Endothelium -dependent flow-mediated dilation of the brachial artery by ultrasound and fingertip tonometry at baseline and 5-minute cuff occlusion of the upper arm. | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in endoplasmic reticulum stress | Endothelial cells will be collected utilizing a J-wire inserted into an arm vein with an 18 gauge catheter using sterile technique and local anesthesia. ER stress will be measured by the study of early and chronic markers of ER stress activation by western blotting and PCR techniques. | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 
| Change in endothelial function | Endothelial cells will be collected utilizing a J-wire inserted into an arm vein with an 18 gauge catheter using sterile technique and local anesthesia. Endothelial function will be measured by the study of endothelial nitric oxide synthase activation and nitric oxide production | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 
| Change in fasting glucose | The blood sample will be processed to measure fasting glucose levels | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 
| Change in insulin levels | The blood sample will be processed to measure insulin levels | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 
| Change in lipid levels | The blood sample will be processed to measure lipids levels including total cholesterol, LDL, HDL and triglycerides | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tauroursodeoxycholic acid (TUDCA), Endothelial function in humans, Endoplasmic Reticulum Stress