search
Back to results

Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance

Primary Purpose

HIV Related Insulin Resistance, Protease Inhibitor Related Insulin Resistance, Endoplasmic Reticulum Stress

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tauroursodeoxycholic acid
Placebo tablet
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for HIV Related Insulin Resistance focused on measuring HIV, Protease inhibitor, insulin resistance, Tauroursodeoxycholic acid

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • HIV+
  • receiving protease inhibitor containing antiretroviral therapy for >6 months
  • Undetectable viral load

  • insulin resistant

    1. impaired fasting glucose (fasting blood glucose>100mg/dl)
    2. impaired glucose tolerance (blood glucose >140mg/dl at 2 hours during oral glucose tolerance testing).
  • abstained from medications that affect glucose (e.g. prednisone, growth hormone)
  • stable medications for >3 months

Exclusion Criteria:

  • weight loss of >5% of body weight in prior 6 months
  • active gastrointestinal disease (gallstones, pancreatitis, hepatitis, diarrhea)
  • use of anti-diabetic medications
  • cardiovascular disease (uncontrolled hypertension, heart attack, heart failure, prior endocarditis)
  • history of or active substance abuse
  • blood clotting disorder or taking medications that affect blood clotting (e.g. coumadin, warfarin)
  • pregnant, planning to become pregnant or lactating
  • unable to give informed consent

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

tauroursodeoxycholic acid

placebo

Arm Description

This group will receive 1.75 grams per day of tauroursodeoxycholic acid given once daily for 30 days.

This group will receive a placebo tablet that is identical to the treatment group except that it does not contain tauroursodeoxycholic acid. The pills will be taken once daily for 30 days.

Outcomes

Primary Outcome Measures

Glucose Uptake
We will examine the ability of insulin to cause muscle to take up insulin. Each subject will receive intravenous insulin for 6 hours to see how much sugar needs to be given intravenously to keep the blood sugar normal, a measure called glucose uptake. We will compare glucose uptake measured as the amount of 20% dextrose that is needed to keep the blood sugar at ~100mg/dl during insulin infusion before and after 30 days of treatment with drug or placebo.

Secondary Outcome Measures

Body Composition
We will measure how much fat is present in each subject before and after treatment with TUDCA or placebo.
Liver Fat
We will use MRI to measure the relative (%) amount of fat in each subject's liver before and after 30 days of treatment. This will allow us to determine if the drug reduces liver fat. This is calculated by subtracting the amount of fat in the liver at the beginning of the study from the amount of fat in the liver after 30 days of treatment. Subjects who have claustrophobia or are unable to undergo MRI will not have this measure performed. Due to these reasons liver MRS was only performed in 10 patients in the tauroursodeoxycholic acid group and 9 subjects in the placebo group
Liver Function Tests
We will measure liver function tests before and after the study drug to ensure that no abnormalities in liver function occurs with the drug.

Full Information

First Posted
June 11, 2013
Last Updated
January 23, 2020
Sponsor
Washington University School of Medicine
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
search

1. Study Identification

Unique Protocol Identification Number
NCT01877551
Brief Title
Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance
Official Title
Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
September 2013 (Actual)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Rates of cardiovascular disease and diabetes are more than 2-fold greater in HIV infected people than the general population. Protease inhibitor booster antiretroviral therapy (PI-ART) which is used by ~50% of HIV infected people in the USA is an established risk factor for diabetes. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile salt, improves insulin sensitivity in HIV uninfected subjects, although the mechanisms for these benefits are unclear. This study will explore the hypothesis that TUDCA will improve insulin action in people with HIV who are receiving PI-ART. Further, this project will clarify the molecular mechanisms responsible for these improvements potentially benefiting society, irrespective of HIV status.
Detailed Description
The purpose of this study is to determine if, and through which mechanisms, tauroursodeoxycholic acid improves insulin sensitivity in subjects with protease-inhibitor associated insulin resistance. The investigators will perform body composition analysis by using a DEXA machine, liver fat measurement by using an MRI, and hyperinsulinemic euglycemic clamp procedures in 48 HIV infected, insulin-resistant/prediabetic subjects before and after 30 days of treatment with tauroursodeoxycholic acid or matching placebo. Biopsies of adipose tissue and skeletal muscle will be taken during fasting conditions and during insulin infusion, before and after treatment to measure markers of endoplasmic reticulum stress and thyroid hormone deiodinase. Outcome measures: The primary outcome measures will be change in glucose clearance during insulin infusion, change in markers of endoplasmic reticulum stress and change in content of D2 in muscle.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Related Insulin Resistance, Protease Inhibitor Related Insulin Resistance, Endoplasmic Reticulum Stress
Keywords
HIV, Protease inhibitor, insulin resistance, Tauroursodeoxycholic acid

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tauroursodeoxycholic acid
Arm Type
Active Comparator
Arm Description
This group will receive 1.75 grams per day of tauroursodeoxycholic acid given once daily for 30 days.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
This group will receive a placebo tablet that is identical to the treatment group except that it does not contain tauroursodeoxycholic acid. The pills will be taken once daily for 30 days.
Intervention Type
Drug
Intervention Name(s)
Tauroursodeoxycholic acid
Other Intervention Name(s)
taurolite, tudcabil
Intervention Description
The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.
Intervention Type
Other
Intervention Name(s)
Placebo tablet
Intervention Description
The placebo group will receive a placebo tablet that is identical to the treatment group except that it does not contain tauroursodeoxycholic acid. The pills will be taken once daily for 30 days.
Primary Outcome Measure Information:
Title
Glucose Uptake
Description
We will examine the ability of insulin to cause muscle to take up insulin. Each subject will receive intravenous insulin for 6 hours to see how much sugar needs to be given intravenously to keep the blood sugar normal, a measure called glucose uptake. We will compare glucose uptake measured as the amount of 20% dextrose that is needed to keep the blood sugar at ~100mg/dl during insulin infusion before and after 30 days of treatment with drug or placebo.
Time Frame
Glucose uptake is measured at baseline and 30 days after study intervention
Secondary Outcome Measure Information:
Title
Body Composition
Description
We will measure how much fat is present in each subject before and after treatment with TUDCA or placebo.
Time Frame
Pre-Treatment and Post 30 day-Treatment
Title
Liver Fat
Description
We will use MRI to measure the relative (%) amount of fat in each subject's liver before and after 30 days of treatment. This will allow us to determine if the drug reduces liver fat. This is calculated by subtracting the amount of fat in the liver at the beginning of the study from the amount of fat in the liver after 30 days of treatment. Subjects who have claustrophobia or are unable to undergo MRI will not have this measure performed. Due to these reasons liver MRS was only performed in 10 patients in the tauroursodeoxycholic acid group and 9 subjects in the placebo group
Time Frame
Pre-Treatment and Post 30 day-Treatment
Title
Liver Function Tests
Description
We will measure liver function tests before and after the study drug to ensure that no abnormalities in liver function occurs with the drug.
Time Frame
Pre-Treatment and Post 30 day-Treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV+ receiving protease inhibitor containing antiretroviral therapy for >6 months Undetectable viral load insulin resistant impaired fasting glucose (fasting blood glucose>100mg/dl) impaired glucose tolerance (blood glucose >140mg/dl at 2 hours during oral glucose tolerance testing). abstained from medications that affect glucose (e.g. prednisone, growth hormone) stable medications for >3 months Exclusion Criteria: weight loss of >5% of body weight in prior 6 months active gastrointestinal disease (gallstones, pancreatitis, hepatitis, diarrhea) use of anti-diabetic medications cardiovascular disease (uncontrolled hypertension, heart attack, heart failure, prior endocarditis) history of or active substance abuse blood clotting disorder or taking medications that affect blood clotting (e.g. coumadin, warfarin) pregnant, planning to become pregnant or lactating unable to give informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominic N. Reeds, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20522594
Citation
Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, Patterson BW, Horton JD, Mittendorfer B, Hotamisligil GS, Klein S. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010 Aug;59(8):1899-905. doi: 10.2337/db10-0308. Epub 2010 Jun 3.
Results Reference
background
Links:
URL
http://actu.im.wustl.edu
Description
Washington University AIDS Clinical Trials Unit

Learn more about this trial

Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance

We'll reach out to this number within 24 hrs