HIV Related Insulin ResistanceNCT01877551
Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance
A study testing Tauroursodeoxycholic acid in people with HIV Related Insulin Resistance and Protease Inhibitor Related Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Related Insulin Resistance, Protease Inhibitor Related Insulin Resistance, Endoplasmic Reticulum Stress
- What is being tested?
- Tauroursodeoxycholic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to May 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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.
Read the 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
- Being tested
- Tauroursodeoxycholic acid, Placebo tablet
- Keywords
- HIV, Protease inhibitor, insulin resistance, Tauroursodeoxycholic acid
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tauroursodeoxycholic acidDrug
Also called taurolite, tudcabil
The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.
Placebo tabletOther
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.
| Study group | Role | What they receive |
|---|---|---|
| tauroursodeoxycholic acid | Active comparator | This group will receive 1.75 grams per day of tauroursodeoxycholic acid given once daily for 30 days. Receives: Drug: Tauroursodeoxycholic acid |
| placebo | Placebo comparator | 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. Receives: Other: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Glucose uptake is measured at baseline and 30 days after study intervention
Secondary outcomes (3)
Body Composition
We will measure how much fat is present in each subject before and after treatment with TUDCA or placebo.
Measured: Pre-Treatment and Post 30 day-Treatment
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
Measured: Pre-Treatment and Post 30 day-Treatment
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.
Measured: Pre-Treatment and Post 30 day-Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2013 (estimated)
- Study startSep 2013
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV Related Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Dominic N. Reeds, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01877551
- Sponsor's protocol ID
- 201306105
- Other IDs
- R01DK096982
- Status last verified
- Jan 2020
- First submitted
- 11 Jun 2013
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20522594
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance
- ClinicalTrials.gov ID
- NCT01877551
- Acronym / sponsor ID
- 201306105
- Conditions
- HIV Related Insulin Resistance, Protease Inhibitor Related Insulin Resistance, Endoplasmic Reticulum Stress
- Keywords
- HIV, Protease inhibitor, insulin resistance, Tauroursodeoxycholic acid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Sep 2013 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 13 Jun 2013 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tauroursodeoxycholic acid | Active comparator | Drug: Tauroursodeoxycholic acidThis group will receive 1.75 grams per day of tauroursodeoxycholic acid given once daily for 30 days. |
| placebo | Placebo comparator | Other: Placebo tabletThis 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HIV+
- receiving protease inhibitor containing antiretroviral therapy for >6 months
- Undetectable viral load
- insulin resistant
- abstained from medications that affect glucose (e.g. prednisone, growth hormone)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tauroursodeoxycholic acidAlso: taurolite, tudcabilThe intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days. | Drug | tauroursodeoxycholic acid |
| Placebo tabletThe 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. | Other | placebo |
Primary outcome
Glucose Uptake
Time frame: Glucose uptake is measured at baseline and 30 days after study intervention
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.
3 secondary outcomes
Body Composition
Time frame: Pre-Treatment and Post 30 day-Treatment
Liver Fat
Time frame: Pre-Treatment and Post 30 day-Treatment
Liver Function Tests
Time frame: Pre-Treatment and Post 30 day-Treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20522594Kars 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.
- Washington University AIDS Clinical Trials UnitLink provided by the sponsor.
Related trials for HIV Related Insulin Resistance
RecruitingObservational study
The Role of Ectopic Fat and Heart Attack Risk in HIV
Cardiometabolic Syndrome, Hiv
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominic N. Reeds, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tauroursodeoxycholic acid in people with HIV Related Insulin Resistance and Protease Inhibitor Related Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose Uptake (time frame: Glucose uptake is measured at baseline and 30 days after study intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01877551, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.