Trial Outcomes & Findings for Effect of Endoplasmic Reticulum Stress on Metabolic Function (NCT NCT00771901)

Results Overview

Fat mass (%)

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

101 participants

Primary outcome timeframe

Baseline and four weeks

Results posted on

2018-05-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid 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.	Sodium Phenylbutyrate Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.
Overall Study STARTED	10	10	10
Overall Study COMPLETED	10	10	6
Overall Study NOT COMPLETED	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid 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.	Sodium Phenylbutyrate Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.
Overall Study Dissat w/# of study medication (40/day)	0	0	4

Baseline Characteristics

Effect of Endoplasmic Reticulum Stress on Metabolic Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid n=10 Participants 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.	Sodium Phenylbutyrate n=6 Participants Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	26 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	49 years STANDARD_DEVIATION 14 • n=5 Participants	47 years STANDARD_DEVIATION 9 • n=7 Participants	49 years STANDARD_DEVIATION 8 • n=5 Participants	47 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	6 participants n=5 Participants	26 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and four weeks

Fat mass (%)

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid n=10 Participants 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.	Sodium Phenylbutyrate n=6 Participants Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.
Body Composition Before Intervention	39 percentage Standard Deviation 7	39 percentage Standard Deviation 8	37 percentage Standard Deviation 6
Body Composition After Intervention	39 percentage Standard Deviation 7	39 percentage Standard Deviation 8	39 percentage Standard Deviation 7

SECONDARY outcome

Timeframe: Baseline and four weeks

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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid n=10 Participants 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.	Sodium Phenylbutyrate n=7 Participants Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.
Insulin Sensitivity in the Liver Before Intervention	0.010 100/ (µmol/min * uIU/mL) Standard Deviation 0.007	0.009 100/ (µmol/min * uIU/mL) Standard Deviation 0.004	0.008 100/ (µmol/min * uIU/mL) Standard Deviation 0.003
Insulin Sensitivity in the Liver After Intervention	0.008 100/ (µmol/min * uIU/mL) Standard Deviation 0.004	0.012 100/ (µmol/min * uIU/mL) Standard Deviation 0.006	0.009 100/ (µmol/min * uIU/mL) Standard Deviation 0.003

SECONDARY outcome

Timeframe: Baseline and four weeks

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Subjects will be given a placebo rather than tauroursodeoxycholic acid. placebo: 7 pills daily for 4 weeks	Tauroursodeoxycholic Acid n=8 Participants 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.	Sodium Phenylbutyrate n=5 Participants Subjects will receive sodium phenylbutyrate for four weeks. sodium phenylbutyrate: 20g/day for four weeks.
VLDL-triglyceride (TG) Concentration After Intervention	0.58 mmol/l Standard Deviation 0.33	0.75 mmol/l Standard Deviation 0.56	0.97 mmol/l Standard Deviation 0.18
VLDL-triglyceride (TG) Concentration Before Intervention	0.57 mmol/l Standard Deviation 0.33	0.74 mmol/l Standard Deviation 0.50	0.89 mmol/l Standard Deviation 0.25

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Tauroursodeoxycholic Acid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sodium Phenylbutyrate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Samuel Klein, M.D.

Washington University School of Medicine in Saint Louis, Missouri

Phone: 314-362-8708

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place