Diabetes Mellitus, Type 2, Insulin Response, Endothelial Dysfunction
Conditions
Keywords
Tauroursodeoxycholic acid (TUDCA), Endothelial function in humans, Endoplasmic Reticulum Stress
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTTauroursodeoxycholic acid
Tauroursodeoxycholic acid is an ambiphilic bile acid. It is the taurine conjugate form of ursodeoxycholic acid.
Sponsors
Boston University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in vascular function | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in endoplasmic reticulum stress | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 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. |
| Change in endothelial function | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | 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 |
| Change in fasting glucose | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | The blood sample will be processed to measure fasting glucose levels |
| Change in insulin levels | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | The blood sample will be processed to measure insulin levels |
| Change in lipid levels | before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period | The blood sample will be processed to measure lipids levels including total cholesterol, LDL, HDL and triglycerides |
Countries
United States
Outcome results
None listed