Clinical trial NCT04350346: The Comparative Analysis Between Motilitone and Gasmotin for the Symptom Relief in Gallstone Patients With Functional Dyspepsia
Official title: A Prospective, Randomized Controlled Trial of the Comparative Analysis Between Motilitone and Gasmotin for the Symptom Relief in Gallstone Patients With Functional Dyspepsia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gallstone
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2020-04-17
Enrollment: 70
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: * (Cause of cholelithiasis) Recently, the average age has increased, and the occurrence of gallstones has increased as the dietary life has been westernized due to the improvement of socio-economic level. When cholesterol increases, the occurrence of gallstones increases. Factors include high-calorie high-fat diet, increasing age, women, pregnant women, obesity, and oral contraceptives. There are cases. As another cause, gallstones occur well even when bile stasis occurs due to a decrease in motility of the gallbladder. These are conditions that lower mobility. And cholelithiasis has a genetic tendency in about 30%. In addition, since the eating habits of the family are similar, the genetic factors and the eating habits overlap, which often leads to the occurrence of cholelithiasis in the family.
* (symptoms of cholelithiasis) In most cases, complaints of non-specific digestive system symptoms, such as abdominal bloating, nausea, and especially indigestion after fatty diet, are often observed. According to domestic reports, the nonspecific symptoms complained by patients with cholelithiasis were indigestion, flatulence, frequent belching, nausea, loss of appetite, diarrhea, and vomiting. In general, many healthy people without gallstones complain of non-specific digestive system symptoms in 50% of cases, and there is a possibility that functional gastrointestinal diseases such as dyspepsia, peptic ulcer, and gastritis may be accompanied by these digestive system symptoms. It is difficult to know whether it is unrelated to gallstones. Symptoms caused by typical cholelithiasis usually have a characteristic that they often improve on their own after a few hours, and the start and end of the symptoms are relatively clear and repeatedly occur. In addition, various symptoms are displayed depending on the presence or absence of inflammation and progression.
* (Principle of treatment of cholelithiasis)

  1. Medical treatment: Medical treatment of gallstones is a method of dissolving using drugs to treat cholesterol gallstones in gallbladder stones. In 1973, Nakano et al. \[1\] published the first example of dissolving cholesterol gallstones using ursodeoxycholic acid (UDCA). Currently, UDCA is the only drug administered to patients with asymptomatic or mild symptoms of cholelithiasis in actual clinical practice, and there is no specific prescription drug.
  2. Surgical treatment: In the case of indications of cholecystectomy, acute cholecystitis, severe symptoms, chronic cholecystitis with severe thickening of the gallbladder wall, repeated and severe symptoms, porcelain gallbladder, Patients with gallstones of 3 cm or more in size, patients with anomalous pancreato-biliary duct unions, or gallbladder polyps.
* (Study on increasing gallbladder contractility) So far, there have been studies that some drugs increase or decrease gallbladder contractility. Catnach SM et al. \[2\] reported that erythromycin increased gallbladder contractility in patients with autonomic neuropathy due to diabetes. Sengupta S et al. \[3\] reported that indoramin (α-adrenergic antagonist), a prokinetic agent, increased gallbladder contractility in patients with cholelithiasis, resulting in a significant decrease in gallbladder volume.

Motilitone® developed in Korea is a gastrointestinal motility stimulator that stimulates 5-HT4 receptors to increase acetylcholine secretion and has a mechanism of contracting smooth muscles, improving symptoms in patients with functional dyspepsia in cholelithiasis It is expected to be able to give, and it is thought to have the effect of preventing the crystallization of bile acids due to an increase in the gallbladder contractility, thereby preventing the formation of gallstones and preventing newly generated gallstones.

To date, there are no special drugs for dyspepsia or pain improvement in patients with cholelithiasis. It is hypothesized that administration of motilitone® will increase the contractile capacity of the gallbladder, thereby improving digestion and preventing further formation of gallstones. As a control group, Gasmotin® was administered to improve functional dyspepsia, and the degree of symptom improvement was measured and compared by completing the Symptom Score Questionnaire for Indigestion between the two groups.

Detailed description: At Severance Hospital, patients with cholelithiasis with symptoms of indigestion are divided into the Motilitone® and Gasmotin® groups. Provide sufficient oral and written explanation of the clinical trial and obtain consent from the patient who has revealed his willingness to participate. Randomization uses random numbers, and patient assignment by random numbers is managed by a third party who does not have direct contact with the patient or clinical history, and after obtaining consent, the group according to the random number is given and medication is given. It is provided to. Each drug is prescribed for 6 months. The symptom score check should be completed at the first outpatient visit(3 months after administration). We will Check the following items through abdominal ultrasound examination 6 months after administration.

: Gallbladder wall thickening presence and extent, number of gallstones, maximum diameter of gallstones, presence or absence of sludge. The general blood test (CBD) and general chemical test (SMA) are conducted three times at the first outpatient visit(3 months after administration), and the research expenses for 3 months and 6 months are supported by the research fund. In the final analysis, we compare the symptom scores between the two groups through the Student T-test, and compare the blood test and ultrasound using the Chi-square test. We want to confirm the following three things through this study. ① In patients with cholelithiasis with symptoms of dyspepsia, prospective data on the degree of symptom improvement following motilitone administration can be obtained. ② It is possible to evaluate the degree of relief or exacerbation of gallstones through ultrasound examination. ③ It is expected that it will be effective in improving symptoms and alleviating cholelithiasis in patients with dyspeptic cholelithiasis due to increased gallbladder contractility of motilitone.

Eligibility criteria: Inclusion Criteria:

1. 19 years old to under 75
2. Patients with dyspepsia in patients with cholelithiasis
3. Patients who consented to this study and conducted questionnaires and tests during follow up

Exclusion Criteria:

1. asymptomatic cholelithiasis
2. Gallstones over 3cm
3. Acute cholecystitis requires surgery
4. pregnant women
5. porcelain gallbladder
6. Chronic cholecystitis with severe thickening of the gallbladder wall
7. Patients with anomalous pancreato-biliary duct union,
8. When other physicians believe that surgery is necessary
9. Patients with a history of hypersensitivity to "motilitone" or its components

   ; Since this drug contains lactose, galactose intolerance, Patients with genetic problems such as Lapp lactase deficiency or glucose-galactose malabsorption.
10. Hepatitis patients (Hepatitis carriers, cirrhosis patients) or suspected liver failure (AST, ALT levels are 1.5 times or more of normal values)

Primary outcomes:
measure: Check symptom improvement
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of WBC count (10^3/µL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of RBC count (10^6/µL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Hemoglobin (g/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of BUN (mg/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Glucose (mg/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Albumin (g/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Total bilirubin (mg/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Direct bilirubin (mg/dL), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Amylase (U/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Lipase (U/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Sodium (mmol/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Potassium (mmol/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Alkaline phosphate (IU/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
measure: Changes in serum concentrations of Gamma-glutamyltransferase (IU/L), before and after the administration
timeFrame: 3months (At the first outpatient visit 3months after administration)
Secondary outcomes:
measure: Abdominal ultrasound examination - Change of Gallbladder wall thickening
timeFrame: 6months (At the second outpatient visit 6months after administration)
measure: Abdominal ultrasound examination - Gallbladder wall extent
timeFrame: 6months (At the second outpatient visit 6months after administration)
measure: Abdominal ultrasound examination - Number of gallstones
timeFrame: 6months (At the second outpatient visit 6months after administration)
measure: Abdominal ultrasound examination - Maximum diameter of gallstones
timeFrame: 6months (At the second outpatient visit 6months after administration)
measure: Abdominal ultrasound examination - Presence or Absence of sludge
timeFrame: 6months (At the second outpatient visit 6months after administration)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Department of Surgery, Severance hospital
Study officials:
References:
citation: Catnach SM, Ballinger AB, Stevens M, Fairclough PD, Trembath RC, Drury PL, Watkins PJ. Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy. Gut. 1993 Aug;34(8):1123-7. doi: 10.1136/gut.34.8.1123.
citation: Sengupta S, Modak P, McCauley N, O'Donnell LJ. Prokinetic effect of alpha-adrenergic antagonist, and beta-adrenergic antagonist on gall-bladder motility in humans with gall-stone disease. Eur J Gastroenterol Hepatol. 2007 Jul;19(7):581-3. doi: 10.1097/MEG.0b013e32811ec044.