Thyroid Hormones Homeostasis and Energy Metabolism Changes During Stimulation of Endogenously Secreted Bile Acids (BAs)

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00706381
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 4
• Duration (Months): 49.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Postprandial thermogenesis, or thermic effect of food are terms that describe the increase in utilization of energy by the human body following a meal. The mechanisms involved in this process are believed to differ according to the type of food consumed, whether fat, protein or carbohydrate.

The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a meal, play an important role in the absorption of fat and the management of cholesterol stores in the body. Recent studies suggest that BAs may also serve as regulators of energy expenditure (consumption) in the cells of our body by increasing the production of T3, an active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which our bodies burn calories thereby generating heat. Although this process has been shown to be effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans is poorly understood. Thus we do not know whether endogenous (produced by the body) or exogenous (taken as medication) BAs play a significant role in the maintenance of body weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing energy expenditure via the production of the active form of thyroid hormone.

This randomized, cross-over study will look at changes in thyroid hormones and energy consumption in response to stimuli of endogenous BA secretion including dietary content, and to the intake of pharmacological doses of bile acids.

Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a 6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate intervention. During the following three days, the study subjects will again be randomized to receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA (ursodiol) with similar metabolic chamber stays and cross-over design.

The data gathered from this study will provide greater insight into the physiological and molecular mechanism(s) regulating the relation between endogenous bile acid secretion and energy metabolism in response to meals, as well as the role of BAs per se on energy metabolism.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Sincalide; Drug: Ursodiol; Procedure: Fat Meal; Procedure: Carb meal; Drug: Placebo	Phase 3

Detailed Description

Postprandial thermogenesis, or thermic effect of food are terms that describe the increase in utilization of energy by the human body following a meal. The mechanisms involved in this process are believed to differ according to the type of food consumed, whether fat, protein or carbohydrate.

The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a meal, play an important role in the absorption of fat and the management of cholesterol stores in the body. Recent studies suggest that BAs may also serve as regulators of energy expenditure (consumption) in the cells of our body by increasing the production of T3, an active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which our bodies burn calories thereby generating heat. Although this process has been shown to be effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans is poorly understood. Thus we do not know whether endogenous (produced by the body) or exogenous (taken as medication) BAs play a significant role in the maintenance of body weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing energy expenditure via the production of the active form of thyroid hormone.

This randomized, cross-over study will look at changes in thyroid hormones and energy consumption in response to stimuli of endogenous BA secretion including dietary content, and to the intake of pharmacological doses of bile acids.

Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a 6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate intervention. During the following three days, the study subjects will again be randomized to receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA (ursodiol) with similar metabolic chamber stays and cross-over design.

The following parameters will be recorded and compared to placebo:

Energy expenditure

Substrate utilization

Spontaneous movements

Skin and core temperature

Serial changes in circulating thyroid hormones

Serial changes in bile acid serum concentrations

The data gathered from this study will provide greater insight into the physiological and molecular mechanism(s) regulating the relation between endogenous bile acid secretion and energy metabolism in response to meals, as well as the role of BAs per se on energy metabolism.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: Thyroid Hormones Homeostasis and Energy Metabolism Changes During Stimulation of Endogenously Secreted Bile Acids (BAs)
• Study Start Date: Jun 23, 2008
• Actual Primary Completion Date: Aug 21, 2012
• Actual Study Completion Date: Aug 21, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1: Carb meal, fat meal, sincalide, placebo, urso Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, and IV placebo + PO Ursodiol 15mg/kg day 5	Drug: Sincalide; Drug: Ursodiol; Procedure: Fat Meal; 600 calorie meal containing 72% fat, 8% protein, and 20% carbohydrate; Procedure: Carb meal; 600 calorie meal containing 100% carbohydrate; Drug: Placebo; IV and/or oral placebo
Experimental: 2: Fat meal, carb meal, sincalide, placebo, urso Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Drug: Sincalide; Drug: Ursodiol; Procedure: Fat Meal; 600 calorie meal containing 72% fat, 8% protein, and 20% carbohydrate; Procedure: Carb meal; 600 calorie meal containing 100% carbohydrate; Drug: Placebo; IV and/or oral placebo
Experimental: 3: Carb meal, fat meal, placebo, sincalide, urso Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Drug: Sincalide; Drug: Ursodiol; Procedure: Fat Meal; 600 calorie meal containing 72% fat, 8% protein, and 20% carbohydrate; Procedure: Carb meal; 600 calorie meal containing 100% carbohydrate; Drug: Placebo; IV and/or oral placebo
Experimental: 4: Fat meal, carb meal, placebo, sincalide, urso Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, the IV placebo + PO Ursodiol 15mg/kg day 5	Drug: Sincalide; Drug: Ursodiol; Procedure: Fat Meal; 600 calorie meal containing 72% fat, 8% protein, and 20% carbohydrate; Procedure: Carb meal; 600 calorie meal containing 100% carbohydrate; Drug: Placebo; IV and/or oral placebo

Outcome Measures

Primary Outcome Measures

1. Energy Expenditure [6 hours]

   Energy expenditure is measured over 6 hours in a respiratory chamber for each intervention and placebo.

2. Bile Acid [6 hours]

   Bile acid is measured at 0, 60, 90 and 360 minutes during a 6 hour stay in in a respiratory chamber for each intervention and placebo. The mean of these 4 values is then calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Age greater than or equal to18 years, male or female

Written informed consent

EXCLUSION CRITERIA:

Hypo- or hyperthyroidism (history or serum thyroid-stimulating hormone (TSH) greater than 5.0 or less than 0.4 miU/L)

Blood pressure greater than 140/90 mmHg (26) or receiving antihypertensive therapy

History of cardiovascular disease

BMI less than or equal to 20 or greater than or equal to 27 Kg/m(2)

Diabetes mellitus (fasting serum glucose greater than or equal to 126 mg/dL)

Hyperlipidemia (serum total cholesterol greater than or equal to 240 mg/dL, triglycerides greater than or equal to 220 mg/dL, and/or use of antilipemic therapy)

Liver disease or ALT serum concentrations greater than 1.5 times the upper laboratory reference limit

Hyperbilirubinemia (serum total bilirubin greater than 1.5 mg/dL)

Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (MDRD equation)

Anemia (Hemoglobin concentration less than or equal to 11.1 g/dL females, and 12.7 g/dL males)

History of cholecystectomy or cholelithiasis (by ultrasound at screening).

History of malabsorption, or food allergies/intolerances that would preclude participant from consuming foods required for study

Claustrophobia

History of illicit drug or alcohol abuse within the last 5 years; current use of illicit drugs (by history) or alcohol (CAGE greater than 3)

Psychiatric conditions or behavior that would be incompatible with safe and successful participation in this study

Current use of medications/dietary supplements/alternative therapies known to alter thyroid function, energy expenditure or bile acid secretion

History of weight loss or weight gain of greater than 3 percent body weight over the past 2 months (self-reported)

Pregnancy/breastfeeding/hormonal contraceptive use and childbirth within the last 6 months

Perimenopausal (as self-described within two years from onset of amenorrhea or current complaints of hot flashes)

Current smoker

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kong Y Chen, Ph.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 14, 2017

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Blaak EE, Hul G, Verdich C, Stich V, Martinez JA, Petersen M, Feskens EF, Patel K, Oppert JM, Barbe P, Toubro S, Polak J, Anderson I, Astrup A, Macdonald I, Langin D, Sørensen T, Saris WH; NUGENOB Consortium. Impaired fat-induced thermogenesis in obese subjects: the NUGENOB study. Obesity (Silver Spring). 2007 Mar;15(3):653-63.
• Hill JO. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr Rev. 2006 Dec;27(7):750-61. Epub 2006 Nov 22. Review.
• Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Review.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00706381
• Other Study ID Numbers: 080165; 08-DK-0165
• First Posted: Jun 27, 2008
• Last Update Posted: Jul 22, 2020
• Last Verified: Aug 4, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): Deiodinase; Bile Acids; Cholecystokinin; Thyroid Hormones; Energy Expenditure; Healthy Volunteer
• Additional relevant MeSH terms: Thyroid Diseases; Ursodeoxycholic Acid

Study Results

Participant Flow

Arm/Group Title	1: Carb Meal, Fat Meal, Sincalide, Placebo, Urso	2: Fat Meal, Carb Meal, Sincalide, Placebo, Urso	3: Carb Meal, Fat Meal, Placebo, Sincalide, Urso	4: Fat Meal, Carb Meal, Placebo, Sincalide, Urso
Arm/Group Description	Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, and IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, the IV placebo + PO Ursodiol 15mg/kg day 5
Period Title: Overall Study
STARTED	10	6	6	9
Intervention 1 (1 Day)	10	6	6	9
Intervention 2 (1 Day)	10	6	6	9
Intervention 3 (1 Day)	10	6	6	9
Intervention 4 (1 Day)	10	5	6	9
Intervention 5 (1 Day)	10	5	5	9
COMPLETED	10	5	5	9
NOT COMPLETED	0	1	1	0

Baseline Characteristics

Arm/Group Title	1: Carb Meal, Fat Meal, Sincalide, Placebo, Urso	2: Fat Meal, Carb Meal, Sincalide, Placebo, Urso	3: Carb Meal, Fat Meal, Placebo, Sincalide, Urso	4: Fat Meal, Carb Meal, Placebo, Sincalide, Urso	Total
Arm/Group Description	Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, and IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV sincalide 0.04mcg/kg + PO placebo day 3, IV placebo + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a 100% carbohydrate meal day 1, then a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, then IV placebo + PO Ursodiol 15mg/kg day 5	Participants randomized to consume a high fat (72% fat, 8% protein, 20% carbohydrate) meal day 1, then a 100% carbohydrate meal day 2, IV placebo + PO placebo day 3, IV sincalide 0.04mcg/kg + PO placebo day 4, the IV placebo + PO Ursodiol 15mg/kg day 5	Total of all reporting groups
Overall Participants	10	6	6	9	31
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	30.8	32.3	33.4	30.4	31.6
Sex: Female, Male (Count of Participants)
Female	6 60%	2 33.3%	3 50%	4 44.4%	15 48.4%
Male	4 40%	4 66.7%	3 50%	5 55.6%	16 51.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	0 0%	0 0%	1 11.1%	2 6.5%
Not Hispanic or Latino	8 80%	6 100%	6 100%	7 77.8%	27 87.1%
Unknown or Not Reported	1 10%	0 0%	0 0%	1 11.1%	2 6.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 10%	0 0%	0 0%	0 0%	1 3.2%
Asian	0 0%	0 0%	0 0%	2 22.2%	2 6.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 20%	2 33.3%	2 33.3%	0 0%	6 19.4%
White	5 50%	4 66.7%	4 66.7%	7 77.8%	20 64.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 20%	0 0%	0 0%	0 0%	2 6.5%

Outcome Measures

1. Primary Outcome

Title	Energy Expenditure
Description	Energy expenditure is measured over 6 hours in a respiratory chamber for each intervention and placebo.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

All participants were to participate in all interventions via cross-over design. One patient did not complete the placebo portion and so was eliminated from analysis in all groups. One other participant did not complete the ursodiol portion.

Arm/Group Title	Carb Meal	Fat Meal	Sincalide	Ursodiol	Placebo
Arm/Group Description	All participants who completed the carbohydrate meal and placebo portions of the study	All participants who completed the high fat meal and placebo portions of the study	All participants who completed the sincalide and placebo portions of the study	All participants who completed the ursodiol and placebo portions of the study	All participants who completed the sincalide portion of the study
Measure Participants	30	30	30	29	30
Mean (Standard Deviation) [kcal/min]	1.37 (0.11)	1.40 (0.09)	1.28 (0.06)	1.27 (0.05)	1.28 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carb Meal, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	7.87
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 9.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fat Meal, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	9.25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 8.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sincalide, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Percent change from placebo
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 6.2
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ursodiol, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 7.2
	Estimation Comments

2. Primary Outcome

Title	Bile Acid
Description	Bile acid is measured at 0, 60, 90 and 360 minutes during a 6 hour stay in in a respiratory chamber for each intervention and placebo. The mean of these 4 values is then calculated.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

All participants were to participate in all interventions via cross-over design. One patient did not complete the placebo portion and so was eliminated from analysis in all groups. One other participant did not complete the ursodiol portion.

Arm/Group Title	Carb Meal	Fat Meal	Sincalide	Ursodiol	Placebo
Arm/Group Description	All participants who completed the carbohydrate meal and placebo portions of the study	All participants who completed the high fat meal and placebo portions of the study	All participants who completed the sincalide and placebo portions of the study	All participants who completed the ursodiol and placebo portions of the study	All participants who completed the placebo portion of the study
Measure Participants	30	30	30	29	30
Mean (Standard Deviation) [mg/dL]	2.89 (0.85)	7.26 (4.6)	2.42 (0.64)	5.17 (1.20)	2.69 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carb Meal, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	40.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 72.8
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fat Meal, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	260.4
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 191.7
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sincalide, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	16.4
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 56.3
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ursodiol, Placebo
	Comments	The percent change from placebo was calculated for each participant and then a t-test was used to test the null hypothesis that this difference was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Percent change from placebo
	Estimated Value	125.7
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 92.2
	Estimation Comments

Adverse Events

Time Frame	5 days
Arm/Group Title	Carb Meal		Fat Meall		Sincalide		Ursodiol		Placebo
Arm/Group Description	All participants who completed the carbohydrate meal portion of the study		All participants who completed the high fat meal portion of the study		All participants who completed the sincalide portion of the study		all participants who completed the ursodiol portion of the study		Oral and IV Placebo
All Cause Mortality
	Carb Meal		Fat Meall		Sincalide		Ursodiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/31 (0%)		0/31 (0%)		0/29 (0%)		0/30 (0%)
Serious Adverse Events
	Carb Meal		Fat Meall		Sincalide		Ursodiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/31 (0%)		0/31 (0%)		0/29 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Carb Meal		Fat Meall		Sincalide		Ursodiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/31 (0%)		0/31 (0%)		0/29 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.