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| Name | Class |
|---|---|
| Ipsen | INDUSTRY |
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This is a human research study looking at the effectiveness of Lanreotide (study medication) in treating small bowel motility disorders. It is similar to a natural hormone somatostatin that is produced in the body in the stomach, duodenum, pancreas and brain. Somatostatin is a growth hormone-inhibiting hormone. Lanreotide is a man made hormone and is a long acting medication that is given once a month. It is marketed with a trade name "Somatuline Depot". It is given deep subcutaneously (deep within the layers of the skin) in the superior external quadrant of the buttock. Injection site will be alternated on subsequent injections.
The investigators hypothesize that in patients with small bowel motility disorders, Lanreotide helps in alleviating the symptoms. Lanreotide is an FDA approved medication for management of acromegaly and neuroendocrine tumors, but has never been used for treating small bowel motility disorders. However, Octreotide which is similar to Lanreotide but is a short acting synthetic somatostatin has been used in few research studies.
If a patient is interested and qualifies for the study then he/she will be explained about the study and signature will be collected on the consent form. Health and social history will be collected. Blood work, urine analysis, pregnancy test (in women of reproductive age group and have the capability of getting pregnant)) will be performed to make sure that patient qualifies for the study and for follow-up during the treatment. Physical examination, ECG, wireless motility capsule testing and hydrogen breath testing will be performed. Patients will be required to complete a questionnaire regarding their health.
The total study duration from the first administration of study drug is 12 weeks. The study medication will be given once a month for 3 months and there is a 1 month follow-up after the last study medication. There will be a screening visit approximately 1 month before the first study drug administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lanreotide | Experimental | Open label |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanreotide | Drug | Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | If the small bowel transit time, as measured by wireless capsule endoscopy, is decreased to < 6hrs, then patient would be considered a responder and that lanreotide is efficacious. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in Symptoms as Accessed by "Patient Assessment of Upper GastroIntestinal Symptom Severity Index" | Improvement in symptoms assessed by improvement in Patient Assessment of Gastrointestinal Disorders Symptom Severity Index(PAGI-SYM) scores. If the PAGI-Sym scores were decreased by at least 0.7 points at 3 months when compared to baseline/pre treatment, then it will be considered that Lanreotide has significantly improved the symptom severity. Higher values represent worse symptoms. The participant rated each of the measured gastrointestinal symptom severity as described 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. PAGI-SYM is a brief (20-items with 6 sub scales) symptom severity questionnaire that captures information on common upper gastrointestinal symptoms which include including Heartburn/regurgitation, Nausea/vomiting, Fullness/early satiety, bloating, Upper abdominal pain, and Lower abdominal pain. The presented data is an average of each sub scale. |
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Inclusion Criteria:
General Exclusion Criteria
Exclusion Criteria for performing wireless motility capsule testing
Exclusion Criteria due to Lanreotide
Current use or recent (within last 7 days) use of acid suppressive therapy, prokinetic agents, laxatives, and opiates, or other agents known to affect gastrointestinal motility.
Disorders associated with presumed small intestinal motility disorders including: scleroderma, intestinal pseudo-obstruction, and autonomic visceral neuropathy (e.g. longstanding diabetes of more than 20 years and/or poorly controlled diabetes (glucose > 250, glycosylated hemoglobin (HbA1c) > 8.5%)
Current use of cyclosporine (Gengraf, Neoral, or Sandimmune), a medicine called bromocriptine (Parlodel, Cycloset), or medicines that lower heart rate, such as beta blockers.
Cardiac arrhythmia based on health history (palpitations, feeling a pause between heartbeats, lightheadedness, passing out, shortness of breath, or chest pain).
Bradycardia and Tachycardia are monitored during every visit to the clinic, using pulse rate.
ECG will be performed during screening visit and during 8th week of the study. The following are accessed with ECG.
Chronic kidney disease (moderate and severe renal impairment as calculated by creatinine clearance of <50 mL/min)
Hepatic Impairment - Subjects with Child-Pugh Class B and Class C.
Significant electrolyte abnormalities: Anything outside of the normal range by +/- 20 % will be considered as abnormal.
Cholelithiasis (Total bilirubin >2x of normal)
Pancreatitis
Hepatitis (Aspartate transaminase (AST), Alanine transaminase (ALT) or Alkaline phosphatase (Alk Ph), greater than upper limit of normal(ULN), Serum albumin <3.0 g/dL unless prothrombin time is within the normal range)
Present cholecystitis
Uncontrolled congestive heart failure
Known hypersensitivity to the study drug
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| Name | Affiliation | Role |
|---|---|---|
| Larry Miller, M.D. | Northwell Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Island Jewish Medical Center | New Hyde Park | New York | 11040 | United States | ||
| Lenox Hill Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1944424 | Background | Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med. 1991 Nov 21;325(21):1461-7. doi: 10.1056/NEJM199111213252102. | |
| 8206395 | Background | Owyang C. Octreotide in gastrointestinal motility disorders. Gut. 1994;35(3 Suppl):S11-4. doi: 10.1136/gut.35.3_suppl.s11. |
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This is an open label non-randomized study. All enrolled participants were checked to see if they meet all the screening requirements to participate. All willing and qualified participants received the study mediation.
First subject was enrolled on 5/11/2017 and the last subject was enrolled on 7/19/2018. All study visits were performed either at a medical clinic or gastroenterology unit. There were also phone follow-ups.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lanreotide | Open label Lanreotide: Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lanreotide | Open label Lanreotide: Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | If the small bowel transit time, as measured by wireless capsule endoscopy, is decreased to < 6hrs, then patient would be considered a responder and that lanreotide is efficacious. | Posted | Mean | Standard Error | minutes | 3 months |
|
|
1 month after last dose, up to 4 months from the start for each subject.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lanreotide | Open label Lanreotide: Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Difficulty swallowing wireless motility capsule pill | Investigations | Systematic Assessment | One patient had difficulty in swallowing the wireless motility capsule and had a sensation that it was struck in the throat. Upon additional examination the subject was fine and was sent home. |
This is a pilot non-randomized study in relatively small number of subjects to identify if Lanreotide will help in alleviating the symptoms and and change gut motility in patients suffering from small bowel motility disorders. A larger study randomized study is required to confirm the findings in this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr.Larry Miller | Northwell health | 5165620334 | lmiller7@northwell.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 28, 2016 | Nov 19, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007410 | Intestinal Diseases |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C060347 | lanreotide |
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|
| 3 months |
| New York |
| New York |
| 10075 |
| United States |
| 9692691 | Background | Edmunds MC, Chen JD, Soykan I, Lin Z, McCallum RW. Effect of octreotide on gastric and small bowel motility in patients with gastroparesis. Aliment Pharmacol Ther. 1998 Feb;12(2):167-74. doi: 10.1046/j.1365-2036.1998.00289.x. |
| 10235603 | Background | Faure C, Goulet O, Ategbo S, Breton A, Tounian P, Ginies JL, Roquelaure B, Despres C, Scaillon M, Maurage C, Paquot I, Hermier M, De Napoli S, Dabadie A, Huet F, Baudon JJ, Larchet M. Chronic intestinal pseudoobstruction syndrome: clinical analysis, outcome, and prognosis in 105 children. French-Speaking Group of Pediatric Gastroenterology. Dig Dis Sci. 1999 May;44(5):953-9. doi: 10.1023/a:1026656513463. |
| 17564625 | Background | Stanghellini V, Cogliandro RF, de Giorgio R, Barbara G, Salvioli B, Corinaldesi R. Chronic intestinal pseudo-obstruction: manifestations, natural history and management. Neurogastroenterol Motil. 2007 Jun;19(6):440-52. doi: 10.1111/j.1365-2982.2007.00902.x. |
| 9414977 | Background | Mann SD, Debinski HS, Kamm MA. Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults. Gut. 1997 Nov;41(5):675-81. doi: 10.1136/gut.41.5.675. |
| 24575015 | Background | Lybaert W. The use of lanreotide autogel(R) in the treatment of intestinal obstruction in a patient with adenocarcinoma. Case Rep Oncol. 2014 Jan 16;7(1):43-6. doi: 10.1159/000358124. eCollection 2014 Jan. |
| 9056054 | Background | Lamrani A, Vidon N, Sogni P, Nepveux P, Catus F, Blumberg J, Chaussade S. Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans. Br J Clin Pharmacol. 1997 Jan;43(1):65-70. doi: 10.1111/j.1365-2125.1997.tb00034.x. |
| 7991964 | Background | Camilleri M. Small bowel motility disorders. Rev Gastroenterol Mex. 1994 Apr-Jun;59(2):120-6. |
| 21106692 | Background | Wang C, Xu H, Chen H, Li J, Zhang B, Tang C, Ghishan FK. Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway. Am J Physiol Cell Physiol. 2011 Feb;300(2):C375-82. doi: 10.1152/ajpcell.00421.2010. Epub 2010 Nov 24. |
| 20410227 | Background | Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S; Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010 Jul;95(7):3141-8. doi: 10.1210/jc.2009-2670. Epub 2010 Apr 21. |
| 20195905 | Background | Wyrwich KW, Mody R, Larsen LM, Lee M, Harnam N, Revicki DA. Validation of the PAGI-SYM and PAGI-QOL among healing and maintenance of erosive esophagitis clinical trial participants. Qual Life Res. 2010 May;19(4):551-64. doi: 10.1007/s11136-010-9620-x. Epub 2010 Feb 27. |
| 15354277 | Background | Revicki DA, Rentz AM, Tack J, Stanghellini V, Talley NJ, Kahrilas P, De La Loge C, Trudeau E, Dubois D. Responsiveness and interpretation of a symptom severity index specific to upper gastrointestinal disorders. Clin Gastroenterol Hepatol. 2004 Sep;2(9):769-77. doi: 10.1016/s1542-3565(04)00348-9. |
| 15651544 | Background | Rentz AM, Kahrilas P, Stanghellini V, Tack J, Talley NJ, de la Loge C, Trudeau E, Dubois D, Revicki DA. Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders. Qual Life Res. 2004 Dec;13(10):1737-49. doi: 10.1007/s11136-004-9567-x. |
| 15479666 | Background | De Giorgio R, Sarnelli G, Corinaldesi R, Stanghellini V. Advances in our understanding of the pathology of chronic intestinal pseudo-obstruction. Gut. 2004 Nov;53(11):1549-52. doi: 10.1136/gut.2004.043968. |
| 23831693 | Background | Iida H, Ohkubo H, Inamori M, Nakajima A, Sato H. Epidemiology and clinical experience of chronic intestinal pseudo-obstruction in Japan: a nationwide epidemiologic survey. J Epidemiol. 2013;23(4):288-94. doi: 10.2188/jea.je20120173. |
| 16131977 | Background | Goulet O, Sauvat F, Jan D. Surgery for pediatric patients with chronic intestinal pseudo-obstruction syndrome. J Pediatr Gastroenterol Nutr. 2005 Sep;41 Suppl 1:S66-8. doi: 10.1097/01.scs.0000180312.55417.8e. No abstract available. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Heart rate | Mean | Standard Deviation | beats/sec |
|
| Systolic Blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Blood Glucose | Mean | Standard Deviation | mg/dL |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Heartburn/regurgitation | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 7 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Nausea/vomiting | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 3 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Fullness/early satiety | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 4 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Bloating | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 2 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Upper abdominal pain | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 2 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Lower abdominal pain | The participant rated each of the measured gastrointestinal symptom severity as described below. (Minimum of 0 and a Maximum of 5.) 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. This subscale accessed the following 2 symptoms -
The computed score is an average of all these gastrointestinal symptoms. | Mean | Standard Deviation | units on a scale |
|
| Gastric emptying time | Mean | Standard Deviation | minutes |
|
| Small bowel transit time | Mean | Standard Deviation | minutes |
|
| Colonic transit time | Mean | Standard Deviation | minutes |
|
| Small bowel and colonic transit time | Mean | Standard Deviation | minutes |
|
| Whole gut transit time | Mean | Standard Deviation | minutes |
|
| Stomach Contractions | Mean | Standard Deviation | Contractions/min |
|
| Stomach Mean Pressure | Mean | Standard Deviation | mm Hg |
|
| Stomach High Pressure | Mean | Standard Deviation | mmHg |
|
| Stomach Low pH | Mean | Standard Deviation | pH |
|
| Stomach Median pH | Mean | Standard Deviation | pH |
|
| Stomach High pH | Mean | Standard Deviation | pH |
|
| Gastric Antrum Motility Index | Gastric antrum is the wider part of the pylorus. It resides upstream from the pyloric canal and downstream from the stomach. Gastric antral motility index = sum of amplitudes × number of contractions + 1. The average motility index in normal subjects is approximately 11. Higher values indicate either increased contractions or increased amplitudes or both. Lower values indicate either decreased contractions or decreased amplitudes or both. | Mean | Standard Deviation | index |
|
| Antrum Contractions | Mean | Standard Deviation | Contractions/min |
|
| Antrum Mean Pressure | Mean | Standard Deviation | mmHg |
|
| Antrum High Pressure | Mean | Standard Deviation | mmHg |
|
| Antrum Low pH | Mean | Standard Deviation | pH |
|
| Antrum Median pH | Mean | Standard Deviation | pH |
|
| Antrum High pH | Mean | Standard Deviation | pH |
|
| Duodenum Motility Index | Duodenal motility index = sum of amplitudes × number of contractions + 1. Higher values indicate either increased contractions or increased amplitudes or both. Lower values indicate either decreased contractions or decreased amplitudes or both. | Mean | Standard Deviation | index |
|
| Duodenum Contractions | Mean | Standard Deviation | Contractions/min |
|
| Duodenum Mean Pressure | Mean | Standard Deviation | mmHg |
|
| Duodenum High Pressure | Mean | Standard Deviation | mmHg |
|
| Duodenum Low pH | Mean | Standard Deviation | pH |
|
| Duodenum Median pH | Mean | Standard Deviation | pH |
|
| Duodenum High pH | Mean | Standard Deviation | pH |
|
| Small Bowel Contractions | Mean | Standard Deviation | Contractions/min |
|
| Small Bowel Mean Pressure | Mean | Standard Deviation | mmHg |
|
| Small Bowel High Pressure | Mean | Standard Deviation | mmHg |
|
| Small Bowel Low pH | Mean | Standard Deviation | pH |
|
| Small Bowel Median pH | Mean | Standard Deviation | pH |
|
| Small Bowel High pH | Mean | Standard Deviation | pH |
|
| Colon Contractions | Mean | Standard Deviation | Contractions/min |
|
| Colon Mean Pressure | Mean | Standard Deviation | mmHg |
|
| Colon High Pressure | Mean | Standard Deviation | mmHg |
|
| Colon Low pH | Mean | Standard Deviation | pH |
|
| Colon Median pH | Mean | Standard Deviation | pH |
|
| Colon High pH | Mean | Standard Deviation | pH |
|
|
|
| Secondary | Improvement in Symptoms as Accessed by "Patient Assessment of Upper GastroIntestinal Symptom Severity Index" | Improvement in symptoms assessed by improvement in Patient Assessment of Gastrointestinal Disorders Symptom Severity Index(PAGI-SYM) scores. If the PAGI-Sym scores were decreased by at least 0.7 points at 3 months when compared to baseline/pre treatment, then it will be considered that Lanreotide has significantly improved the symptom severity. Higher values represent worse symptoms. The participant rated each of the measured gastrointestinal symptom severity as described 0=No symptom, 1=Very Mild Symptom, 2= Mild Symptoms, 3= Moderate symptom, 4=Severe symptom, 5= Very Severe symptom. PAGI-SYM is a brief (20-items with 6 sub scales) symptom severity questionnaire that captures information on common upper gastrointestinal symptoms which include including Heartburn/regurgitation, Nausea/vomiting, Fullness/early satiety, bloating, Upper abdominal pain, and Lower abdominal pain. The presented data is an average of each sub scale. | Posted | Mean | Standard Error | score on a scale | 3 months |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 2 |
| 9 |
|
| Unable to acknowledge the passage of the wireless motility capsule through the feces | Investigations | Systematic Assessment | Subject was not able to acknowledge the passage of the wireless motility capsule through the feces after the end of 4 days after ingestion. An abdominal x-ray was performed to confirm that the capsule was indeed expelled. |
|
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| Title | Measurements |
|---|---|
|
| Bloating |
|
| Upper abdominal pain |
|
| Lower abdominal pain |
|