Insulin ResistanceTUDCA/PBANCT00771901
Effect of Endoplasmic Reticulum Stress on Metabolic Function
A study testing tauroursodeoxycholic acid and sodium phenylbutyrate in people with Insulin Resistance and Diabetes, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Normally, the hormone insulin works to help keep blood sugar normal. However, as a person gains weight, insulin does not work as well and blood sugar tends to be a little higher than normal. This is called "insulin resistance". Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Diabetes, Obesity
- What is being tested?
- tauroursodeoxycholic acid and sodium phenylbutyrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Dec 2014
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI range 30 to 45
- sedentary (defined as regular exercise < 1 h per week or < 2 x/week for the last 6 months)
Who cannot join
- active or previous infection with hepatitis B or C
- liver diseases
- history of alcohol abuse
- current alcohol consumption > 20 g/day
- severe hypertriglyceridemia ( > 400 mg/dL)
- active peptic ulcer disease
- taking cholestyramine or oral contraceptives
- women who are pregnant or lactating
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Normally, the hormone insulin works to help keep blood sugar normal. However, as a person gains weight, insulin does not work as well and blood sugar tends to be a little higher than normal. This is called "insulin resistance".
Two investigational drugs (not approved by the Food and Drug Administration) for the treatment of high lipid levels or insulin resistance are being examined in this study: one drug is called tauroursodeoxycholic acid (TUDCA), the other is called sodium phenylbutyrate (PBA). This study is designed to test if TUDCA and/or PBA is effective in people who are obese with insulin resistance and high lipids. We hypothesize that pharmacologically-induced decreases in ER stress will improve insulin action and hepatic lipid metabolism in obese subjects.
Read the detailed description
A 4-week randomized, controlled trial will be conducted to evaluate the following specific aims in obese subjects:
Determine the effect of treatment with TUDCA or PBA on:
- Body fat distribution: a) intrahepatic triglyceride (IHTG) content, b) intramyocellular triglyceride (IMTG) content, and c) intra-abdominal fat content, assessed by using magnetic resonance spectroscopy and magnetic resonance imaging.
- In vivo insulin sensitivity in adipose tissue (suppression of lipolysis), liver (suppression of glucose production), and skeletal muscle (stimulation of glucose uptake), assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer infusion.
- VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates, assessed by stable isotopically labeled tracer infusion methods.
- Skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo.
- Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo.
- Conditions
- Insulin Resistance, Diabetes, Obesity
- Being tested
- tauroursodeoxycholic acid, placebo, sodium phenylbutyrate
- Keywords
- obesity, insulin resistance, type II diabetes
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Obesity, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tauroursodeoxycholic acidDrug
Also called TUDCA
1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.
placeboOther
7 pills daily for 4 weeks
sodium phenylbutyrateDrug
Also called PBA
20g/day for four weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will be given a placebo rather than tauroursodeoxycholic acid. Receives: Other: placebo |
| tauroursodeoxycholic acid | Experimental | Subjects will receive tauroursodeoxycholic acid for four weeks. Receives: Drug: tauroursodeoxycholic acid |
| PBA | Experimental | Subjects will receive sodium phenylbutyrate for four weeks. Receives: Drug: sodium phenylbutyrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body Composition
Fat mass (%)
Measured: Baseline and four weeks
Secondary outcomes (2)
Insulin Sensitivity in the Liver
HISI (hepatic insulin sensitivity index). HISI is the inverse of the product of endogenous glucose production and plasma insulin concentration and provides an index of how well circulating insulin controls the amount of glucose supplied by the liver. A higher number is indicative of greater insulin sensitivity.
Measured: Baseline and four weeks
VLDL-triglyceride (TG) Concentration
Measured: Baseline and four weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2008 (estimated)
- Study startFeb 2008
- Primary completionDec 2014
- Study completionDec 2014
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 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00771901
- Sponsor's protocol ID
- 07-1114
- Acronym
- TUDCA/PBA
- Status last verified
- Apr 2018
- First submitted
- 10 Oct 2008
- Last updated
- 29 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Endoplasmic Reticulum Stress on Metabolic Function
- ClinicalTrials.gov ID
- NCT00771901
- Acronym / sponsor ID
- TUDCA/PBA / 07-1114
- Conditions
- Insulin Resistance, Diabetes, Obesity
- Keywords
- obesity, insulin resistance, type II diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Feb 2008 (actual)
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 15 Oct 2008 (estimated)
- Results
- Posted 29 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Normally, the hormone insulin works to help keep blood sugar normal. However, as a person gains weight, insulin does not work as well and blood sugar tends to be a little higher than normal. This is called "insulin resistance".
Two investigational drugs (not approved by the Food and Drug Administration) for the treatment of high lipid levels or insulin resistance are being examined in this study: one drug is called tauroursodeoxycholic acid (TUDCA), the other is called sodium phenylbutyrate (PBA). This study is designed to test if TUDCA and/or PBA is effective in people who are obese with insulin resistance and high lipids. We hypothesize that pharmacologically-induced decreases in ER stress will improve insulin action and hepatic lipid metabolism in obese subjects.
Detailed description
A 4-week randomized, controlled trial will be conducted to evaluate the following specific aims in obese subjects:
Determine the effect of treatment with TUDCA or PBA on:
- Body fat distribution: a) intrahepatic triglyceride (IHTG) content, b) intramyocellular triglyceride (IMTG) content, and c) intra-abdominal fat content, assessed by using magnetic resonance spectroscopy and magnetic resonance imaging.
- In vivo insulin sensitivity in adipose tissue (suppression of lipolysis), liver (suppression of glucose production), and skeletal muscle (stimulation of glucose uptake), assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer infusion.
- VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates, assessed by stable isotopically labeled tracer infusion methods.
- Skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo.
- Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: placeboSubjects will be given a placebo rather than tauroursodeoxycholic acid. |
| tauroursodeoxycholic acid | Experimental | Drug: tauroursodeoxycholic acidSubjects will receive tauroursodeoxycholic acid for four weeks. |
| PBA | Experimental | Drug: sodium phenylbutyrateSubjects will receive sodium phenylbutyrate for four weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- BMI range 30 to 45
- sedentary (defined as regular exercise < 1 h per week or < 2 x/week for the last 6 months)
Key exclusion criteria (8 listed)
- active or previous infection with hepatitis B or C
- liver diseases
- history of alcohol abuse
- current alcohol consumption > 20 g/day
- severe hypertriglyceridemia ( > 400 mg/dL)
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: TUDCA1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner. | Drug | tauroursodeoxycholic acid |
| placebo7 pills daily for 4 weeks | Other | Placebo |
| sodium phenylbutyrateAlso: PBA20g/day for four weeks. | Drug | PBA |
Primary outcome
Body Composition
Time frame: Baseline and four weeks
Fat mass (%)
2 secondary outcomes
Insulin Sensitivity in the Liver
Time frame: Baseline and four weeks
VLDL-triglyceride (TG) Concentration
Time frame: Baseline and four weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
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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.
Samuel Klein, MD 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 and sodium phenylbutyrate in people with Insulin Resistance and Diabetes, 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 2 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 29 May 2018. 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 29 May 2018). 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?
Body Composition (time frame: Baseline and four weeks). 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 NCT00771901, 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 29 May 2018.