Gallbladder Functions & Serum Cholecystokinin Levels in Women Diagnosed With Hyperemesis Gravidarum

• Sponsor: Müge Keskin (Other)
• Overall Status: Completed
• CT.gov ID: NCT03950167
• Collaborator: (none)
• Enrollment: 325
• Location: 1
• Actual Duration (Months): 13.7
• Patients Per Site Per Month: 23.8

Study Details

Study Description

Brief Summary

This study evaluates the gallbladder functions and serum cholecystokinin levels in pregnant women diagnosed with hyperemesis gravidarum. Half of the participants are healthy pregnant women and half of the participants are pregnant women diagnosed with hyperemesis gravidarum. Two groups will be compared by means of gallbladder functions and serum cholecystokinin levels.

Condition or Disease	Intervention/Treatment	Phase
Hyperemesis Gravidarum; Pregnancy Related

Detailed Description

Previously gallbladder functions have been observed in human with gallbladder disease. However it has never been evaluated whether there is any difference in gallbladder functions between healthy pregnant women and pregnant women diagnosed with hyperemesis gravidarum. Moreover correlation between hyperemesis gravidarum symptom scores and gallbladder functions has never been assessed. There is also few data comparing serum cholecystokinin levels between healthy pregnant women and those diagnosed with hyperemesis gravidarum. The investigators will measure serum cholecystokinin levels after a fatty meal (100 g chocolate) and compare two groups. In this study the investigators would like to evaluate gallbladder functions and serum cholecystokinin levels in women with hyperemesis gravidarum and compare these with healthy subjects.

Study Design

• Study Type: Observational
• Actual Enrollment: 325 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Gallbladder Functions & Serum Cholecystokinin Levels in Pregnant Women Diagnosed With Hyperemesis Gravidarum
• Actual Study Start Date: Mar 26, 2019
• Actual Primary Completion Date: May 15, 2020
• Actual Study Completion Date: May 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Hyperemesis gravidarum pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Healthy pregnant women Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.

Outcome Measures

Primary Outcome Measures

1. Blood Cholecystokinin (CCK) Levels [Fasting (baseline) and postprandial (15 minutes after the test meal) CCK level]

   a gut hormone released, its level can be measured in blood as fasting level and postprandial

2. Gallbladder (GB) Wall Thickness [fasting and postprandial 45th minute]

   GB wall thickening measured with abdominal ultrasound at fasting and postprandial

3. Gallbladder (GB) Volume [fasting and postprandial 45th minute]

   volume of GB measured with abdominal ultrasound at fasting and postprandial

4. Gallbladder (GB) Ejection Fraction [The fasting and postprandial 45th minute]

   GB ejection fraction measures how much bile gallbladder releases at one time, expressed as percentage

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• gestation week between 6 and 14 weeks,

• singleton pregnancy with a live embryo,

• healthy women without any medical disorders,

Exclusion Criteria

• any systemic disease,

• gallbladder disease

• any psychological disorder that can cause vomiting,

• multiple gestation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ufuk University Hospital	Ankara		Turkey

Sponsors and Collaborators

• Müge Keskin

Investigators

• Principal Investigator: Muge Keskin, Ufuk University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 26, 2021
• Informed Consent Form - Mar 26, 2019

More Information

Publications

None provided.

• Responsible Party: Müge Keskin, Principal investigator, Ufuk University
• ClinicalTrials.gov Identifier: NCT03950167
• Other Study ID Numbers: 20190328
• First Posted: May 15, 2019
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Müge Keskin, Principal investigator, Ufuk University: gallbladder functions; cholecystokinin; hyperemesis gravidarum
• Additional relevant MeSH terms: Hyperemesis Gravidarum

Study Results

Participant Flow

Recruitment Details

This is a prospective cohort study conducted in Ufuk University hospital, Ankara, Turkey (a tertiary center) between March 2019 and May 2020.

Pre-assignment Detail

Excluded (n=275) Not meeting inclusion criteria (n=163) Inclusion criteria were: gestation week between 6 and 14 weeks, singleton pregnancy with a live embryo, age range between 18 and 40 years, healthy women without any medical disorders, Women with any systemic disease, gallbladder disease or any psychological disorder that can cause vomiting, multiple gestation were excluded. Declined to participate (n=112)

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Period Title: Overall Study
STARTED	25	25
COMPLETED	24	22
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women	Total
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Total of all reporting groups
Overall Participants	24	22	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.08 (4.03)	30.91 (4.20)	30.49 (2.11)
Sex: Female, Male (Count of Participants)
Female	24 100%	22 100%	46 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	24 100%	22 100%	46 100%
Region of Enrollment (participants) [Number]
Turkey	24 100%	22 100%	46 100%
age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.91 (4.2)	30.08 (4.03)	30.49 (4.11)
body mass index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	23.95 (3.53)	24.55 (4.72)	24.25 (4.125)
gravidity (gravidity) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [gravidity]	2	2	2
Gestational age (weeks) [Median (Full Range) ]
Median (Full Range) [weeks]	9.07	8.92	8.995
parity (parity) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [parity]	1	1	1

Outcome Measures

1. Primary Outcome

Title	Blood Cholecystokinin (CCK) Levels
Description	a gut hormone released, its level can be measured in blood as fasting level and postprandial
Time Frame	Fasting (baseline) and postprandial (15 minutes after the test meal) CCK level

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Measure Participants	24	22
fasting CCK	53.13 (25.3)	54.55 (25.32)
postprandial CCK	73.61 (30.29)	81.24 (29.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Fasting CCK level difference: hyperemesis group-control group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments	Since this is the first study comparing both CCK levels and GB functions in patients diagnosed with hyperemesis gravidarum (HG) and healthy pregnant women, a power analysis was not feasible.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Postprandial CCK level difference: hyperemesis group-control group

2. Primary Outcome

Title	Gallbladder (GB) Wall Thickness
Description	GB wall thickening measured with abdominal ultrasound at fasting and postprandial
Time Frame	fasting and postprandial 45th minute

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Measure Participants	24	22
fasting GB wall thickness	2.10 (0.57)	2.11 (0.47)
postprandial GB wall thickness	2.51 (0.51)	2.74 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Fasting GB wall thickness: Hyperemesis group-control group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Postprandial GB wall thickness: hyperemesis group-control group

3. Primary Outcome

Title	Gallbladder (GB) Volume
Description	volume of GB measured with abdominal ultrasound at fasting and postprandial
Time Frame	fasting and postprandial 45th minute

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Measure Participants	24	22
fasting GB volume	36.9 (13.8)	33.69 (12.54)
postprandial GB volume	17.29 (8.14)	18.33 (6.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Fasting GB volume: hyperemesis group-control group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Postprandial GB volume: hyperemesis group-control group

4. Primary Outcome

Title	Gallbladder (GB) Ejection Fraction
Description	GB ejection fraction measures how much bile gallbladder releases at one time, expressed as percentage
Time Frame	The fasting and postprandial 45th minute

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyperemesis Gravidarum	Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.	Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
Measure Participants	24	22
Mean (Standard Deviation) [Percantage (%)]	52.06 (19.45)	45.46 (16.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Fasting GB ejection fraction: hyperemesis group-control group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hyperemesis Gravidarum, Healthy Pregnant Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	A p value of <0.05 was accepted as significant in all statistical analyses.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	p value demonstrated above is the calculated value. Postprandial GB ejection fraction: hyperemesis group-control group

Adverse Events

Time Frame	1 year 6 months
Adverse Event Reporting Description	a fatty test meal (100 g milk chocolate) was given to all participants for the evaluation of postprandial cholecystokinin levels and gallbladder parameters including volume and gallbladder wall thickness. Nausea and vomiting are the possible adverse events that may have been observed.
Arm/Group Title	Hyperemesis Gravidarum		Healthy Pregnant Women
Arm/Group Description	pregnant women before 14 weeks of pregnancy diagnosed with hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.		Healthy pregnant women before 14 weeks of pregnancy without hyperemesis gravidarum will be assessed in terms of gallbladder functions and serum cholecystokinin levels after a fatty meal.
All Cause Mortality
	Hyperemesis Gravidarum		Healthy Pregnant Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)
Serious Adverse Events
	Hyperemesis Gravidarum		Healthy Pregnant Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Hyperemesis Gravidarum		Healthy Pregnant Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)
Gastrointestinal disorders
Nausea and vomitting	0/24 (0%)		0/22 (0%)

Limitations/Caveats

Lack of power analysis and inclusion of few patients after assessing eligibility for the study are the limitations.

More Information

Certain Agreements

Principal Investigators are NOT 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.