Lanreotide in the Treatment of Small Bowel Motility Disorders

Intestinal Disease Clinical Trial

Official title:

A Pilot Study to Evaluate Safety and Effectiveness of Lanreotide in the Treatment of Patients With Small Bowel Motility Disorders (SBMD): a Prospective, Non-randomized, Single-center Study of 20 Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03012594
• Other study ID #: HS16-0465
• Status: Completed
• Phase: Phase 2
• Start date: May 11, 2017
• Est. completion date: March 11, 2019

Study information

• Verified date: December 2020
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 11, 2019
• Est. primary completion date: October 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Consecutive patients with evidence of small bowel motility disorders, referred to (or) are patients of the Gastroenterology and Motility Center at Northwell Health System.

2. Aged between 18 and 70 years.

3. Subjects should be capable of understanding the study and be able to give informed consent.

4. Patient having small bowel motility disorder as evidenced by delayed small bowel transit by wireless motility capsule (WMC) testing to > 6 hours.

5. To participate in the study, patients will have to stop taking Octreotide (because it has the same mechanism of action as the study medication) if they are currently taking it; it should be stopped for at least 4 weeks before taking the first dose of this study medication.

General Exclusion Criteria

1. Age <18 or age >70

2. Pregnancy as assessed by urine pregnancy test.

Exclusion Criteria for performing wireless motility capsule testing

1. History of gastric bezoar

2. History of Disorders of swallowing

3. Known or suspected small bowel diverticula, diverticulitis, strictures, fistulas, Crohn's disease, or any other relevant medical comorbidity (e.g. chronic alcohol abuse)

4. Prior intestinal surgery, including Ileocecal(IC) valve resection or gastrointestinal surgeries that create a blind loop (e.g. Bilroth II or Roux-en-Y)

5. History of Severe dysphagia to food or pills

6. A participant who uses an implanted or portable electro-mechanical medical device such as a cardiac pacemaker or infusion pump

7. Inability to be off intestinal transit altering medication for at least one week (e.g. opiates, laxatives, etc.)

8. Any person unable or unwilling to undergo abdominal surgery.

9. BMI > 40.

Exclusion Criteria due to Lanreotide

1. 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.

2. 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%)

3. Current use of cyclosporine (Gengraf, Neoral, or Sandimmune), a medicine called bromocriptine (Parlodel, Cycloset), or medicines that lower heart rate, such as beta blockers.

4. 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.

• Bradycardia <60 beats/min.

• Tachycardia >100 beats/min.

• Atrial Fibrillation - Rapid irregular atrial signal with no real P-waves and irregular ventricular rate.

• Ventricular Fibrillation - Irregular ventricular waveforms.

• Sinus Arrhythmia - Normal beats, but triggered at an irregular interval from 60 to 100 beats per minute, causing varying R-R interval.

• Missed beats.

5. Chronic kidney disease (moderate and severe renal impairment as calculated by creatinine clearance of <50 mL/min)

6. Hepatic Impairment - Subjects with Child-Pugh Class B and Class C.

7. Significant electrolyte abnormalities: Anything outside of the normal range by +/- 20 % will be considered as abnormal.

8. Cholelithiasis (Total bilirubin >2x of normal)

9. Pancreatitis

10. 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)

11. Present cholecystitis

12. Uncontrolled congestive heart failure

13. Known hypersensitivity to the study drug

Related Conditions & MeSH terms

• Disease
• Gastrointestinal Motility Disorder
• Intestinal Disease
• Intestinal Diseases

Intervention

Drug:
• Lanreotide
Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart

Locations

Country	Name	City	State
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Lenox Hill Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Northwell Health	Ipsen

Country where clinical trial is conducted

United States, 

References & Publications (17)

Camilleri M. Small bowel motility disorders. Rev Gastroenterol Mex. 1994 Apr-Jun;59(2):120-6. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Lybaert W. The use of lanreotide autogel® 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. — View Citation

Mann SD, Debinski HS, Kamm MA. Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults. Gut. 1997 Nov;41(5):675-81. — View Citation

Owyang C. Octreotide in gastrointestinal motility disorders. Gut. 1994;35(3 Suppl):S11-4. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	3 months
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.	3 months