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Effect of Endoplasmic Reticulum Stress on Metabolic Function (TUDCA/PBA)

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ClinicalTrials.gov Identifier: NCT00771901
Recruitment Status : Completed
First Posted : October 15, 2008
Results First Posted : May 28, 2018
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Basic Science
Conditions Insulin Resistance
Diabetes
Obesity
Interventions Drug: tauroursodeoxycholic acid
Other: placebo
Drug: sodium phenylbutyrate
Enrollment 101
Recruitment Details Participants will be recruited by reviewing the VFH database pf research subjects and by local postings. Potential subjects will be contacted by telephone for an initial pre-screen, at which time the study is discussed and a brief medical history and concomitant medication list is obtained. ICF will be sent to interested subjects.
Pre-assignment Details Screening tests to determine eligibility included: medical hx & PE, blood tests, resting ECG, OGTT, MRI/MRS/MRE of abdomen/liver, and DEXA scan. Two baseline metabolism studies prior to study drug intervention. There were 67 screen fails, 4 subjects withdrew consent before beginning study intervention.
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Hide Arm/Group Description

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

Period Title: Overall Study
Started 10 10 10
Completed 10 10 6
Not Completed 0 0 4
Reason Not Completed
Dissat w/# of study medication (40/day)             0             0             4
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate Total
Hide Arm/Group Description

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

Total of all reporting groups
Overall Number of Baseline Participants 10 10 6 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 6 participants 26 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
10
 100.0%
6
 100.0%
26
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 6 participants 26 participants
49  (14) 47  (9) 49  (8) 47  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 6 participants 26 participants
Female
6
  60.0%
6
  60.0%
2
  33.3%
14
  53.8%
Male
4
  40.0%
4
  40.0%
4
  66.7%
12
  46.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 6 participants 26 participants
10 10 6 26
1.Primary Outcome
Title Body Composition
Hide Description Fat mass (%)
Time Frame Baseline and four weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Hide Arm/Group Description:

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

Overall Number of Participants Analyzed 10 10 6
Mean (Standard Deviation)
Unit of Measure: percentage
Before Intervention 39  (7) 39  (8) 37  (6)
After Intervention 39  (7) 39  (8) 39  (7)
2.Secondary Outcome
Title Insulin Sensitivity in the Liver
Hide Description 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.
Time Frame Baseline and four weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Hide Arm/Group Description:

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

Overall Number of Participants Analyzed 10 10 7
Mean (Standard Deviation)
Unit of Measure: 100/ (µmol/min * uIU/mL)
Before Intervention 0.010  (0.007) 0.009  (0.004) 0.008  (0.003)
After Intervention 0.008  (0.004) 0.012  (0.006) 0.009  (0.003)
3.Secondary Outcome
Title VLDL-triglyceride (TG) Concentration
Hide Description [Not Specified]
Time Frame Baseline and four weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Hide Arm/Group Description:

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

Overall Number of Participants Analyzed 7 8 5
Mean (Standard Deviation)
Unit of Measure: mmol/l
Before Intervention 0.57  (0.33) 0.74  (0.50) 0.89  (0.25)
After Intervention 0.58  (0.33) 0.75  (0.56) 0.97  (0.18)
Time Frame Adverse event data was collected from the time participants signed the informed consent until 30 days after study completion.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Hide Arm/Group Description

Subjects will be given a placebo rather than tauroursodeoxycholic acid.

placebo: 7 pills daily for 4 weeks

Subjects will receive tauroursodeoxycholic acid for four weeks.

tauroursodeoxycholic acid: 1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Subjects will receive sodium phenylbutyrate for four weeks.

sodium phenylbutyrate: 20g/day for four weeks.

All-Cause Mortality
Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/6 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/6 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Tauroursodeoxycholic Acid Sodium Phenylbutyrate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/6 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Samuel Klein, M.D.
Organization: Washington University School of Medicine in Saint Louis, Missouri
Phone: 314-362-8708
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00771901     History of Changes
Other Study ID Numbers: 07-1114
First Submitted: October 10, 2008
First Posted: October 15, 2008
Results First Submitted: September 15, 2017
Results First Posted: May 28, 2018
Last Update Posted: May 28, 2018