Dose Response of Intravenous Sincalide(CCK-8) for Gallbladder Emptying

Study Overview
=================
Brief Summary
-----------------
This is a clinical research study to establish normal values for the infusion of a synthetic form of the hormone cholecystokinin(CCK-8) for gallbladder emptying. Cholecystokinin is released from the small bowel to stimulate the pancreas and gallbladder to help digest and absorb food. Some people have gallbladder problems and need to be tested with the synthetic cholecystokinin ( Kinevac®, Bracco Diagnostics, Inc.). The aim of this study is to find out how differing amounts and intravenous infusion times of CCK-8 affect gallbladder emptying. The findings in normal subjects will be used to establish normal values that can then be compared with patients with suspected gallbladder disease.

Detailed Description
-----------------
This study enrolled 60 healthy volunteers from four institutions (Johns Hopkins University, Pennsylvania State University, Memorial Health University Medical Center, and Temple University. Subjects had to be healthy men or women 18-65 years old with no gastrointestinal disease as confirmed by initial screening using a modified Mayo Clinic Research Gastrointestinal Disease Screening Questionnaire, and normal results for CBC, metabolic profile, serum amylase and gallbladder ultrasonography. Women could not be enrolled if pregnant. Subjects had 3 infusion studies at least 2 days apart within 3 weeks.

Official Title
-----------------
Dose Response of Intravenous Sincalide (CCK-8) for Gallbladder Emptying

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Experimental Sequence ABC
* Drug: Experimental Sequence ACB
* Drug: Experimental Sequence BAC
* Drug: Experimental Sequence BCA
* Drug: Experimental Sequence CAB
* Drug: Experimental Sequence CBA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females between ages 18-65 years of age with no gastrointestinal disease as screened by the Mayo Clinic GI Disease Screening Questionnaire Subjects with high probability for compliance and completion of the study Normal liver function tests and amylase Normal ultrasound of the gallbladder Exclusion Criteria: Prior GI surgery, excluding appendectomy Surgery within the past 3 months BMI > 35 Female of childbearing age who is not practicing birth control and/or is pregnant or lactating. (Confirm with urine pregnancy test) Cardiovascular, endocrine, renal, gastrointestinal, or other chronic disease likely to affect motility. This includes diabetes, renal insufficiency, gastroesophageal reflux disease, gastroparesis, irritable bowel syndrome, prior peptic ulcer disease. GI symptoms such as heartburn, chest pain, dysphagia, abdominal pain, nausea, vomiting, constipation, diarrhea.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental Sequence ABC<br>CCK-8 0.02 mg/kg over 15 minutes, followed by CCK-8 0.02 mg/kg over 30 minutes, followed by CCK-8 0.02 mg/kg 60 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence ABC<br>* Drug will be given over 15 minutes, followed by infusion over 30 minutes, followed by infusion over 60 minutes<br>* Other names: Sequence ABC;|
| Active Comparator: Experimental Sequence ACB<br>CCK-8 0.02 mg/kg over 15 minutes, followed by CCK-8 0.02 mg/kg over 60 minutes, followed by CCK-8 0.02 mg/kg 30 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence ACB<br>* Drug infused over 15 minutes, followed by infusion over 60 minutes, followed by infusion over 30 minutes<br>* Other names: Sequence ACB;|
| Active Comparator: Experimental Sequence BAC<br>CCK-8 0.02 mg/kg over 30 minutes, followed by CCK-8 0.02 mg/kg over 15 minutes, followed by CCK-8 0.02 mg/kg 60 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence BAC<br>* Drug will be given over 30 min infusion, followed by 15 minute infusion, followed by 60 minute infusion<br>* Other names: Sequence BAC;|
| Active Comparator: Experimental Sequence BCA<br>CCK-8 0.02 mg/kg over 30 minutes, followed by CCK-8 0.02 mg/kg over 60 minutes, followed by CCK-8 0.02 mg/kg 15 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence BCA<br>* Drug will be given over 30 min infusion, followed by 60 minute infusion, followed by 15 minute infusion<br>* Other names: Sequence BCA;|
| Active Comparator: Experimental Sequence CAB<br>CCK-8 0.02 mg/kg over 60 minutes, followed by CCK-8 0.02 mg/kg over 15 minutes, followed by CCK-8 0.02 mg/kg 30 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence CAB<br>* Drug will be given over 60 min infusion, followed by 15 minute infusion, followed by 30 minute infusion<br>* Other names: Sequence CAB;|
| Active Comparator: Experimental Sequence CBA<br>CCK-8 0.02 mg/kg over 60 minutes, followed by CCK-8 0.02 mg/kg over 30 minutes, followed by CCK-8 0.02 mg/kg 15 minutes, with at least 2 days between each infusion | Drug: Experimental Sequence CBA<br>* Drug will be given over 60 min infusion, followed by 30 minute infusion, followed by 15 minute infusion<br>* Other names: Sequence CBA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of Variation (CV) for Gallbladder Ejection Fraction (GBEF) for Each Infusion Method | The primary statistical endpoint was the CV as a measure of variability for the GBEF for each infusion method at the different intervals to determine which sincalide infusion method had the lowest variation. The CV is the SD divided by the mean and is expressed as a percentage and reflects the variability among the values. The infusion method having the lowest CV is considered best as it reflects the lowest variability of the values. | 15, 30, 45, and 60 minutes post drug infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gallbladder Ejection Fraction (GBEF) as a Percent for Each Infusion Method |  | 15, 30, 45 and 60 minutes post-infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CCK infusion, Gallbladder ejection fraction, Normal volunteers