Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance

NCT ID: NCT01877551

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2018-05-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

tauroursodeoxycholic acid

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

Group Type: ACTIVE_COMPARATOR

Tauroursodeoxycholic acid

Intervention Type: DRUG

The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.

placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo tablet

Intervention Type: OTHER

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.

Interventions

Tauroursodeoxycholic acid

The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.

Intervention Type: DRUG

Placebo tablet

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.

Intervention Type: OTHER

Other Intervention Names

taurolite; tudcabil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominic N. Reeds, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20522594 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://actu.im.wustl.edu

Washington University AIDS Clinical Trials Unit

Other Identifiers

R01DK096982

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201306105

Identifier Type: -

Identifier Source: org_study_id