Clinical trial NCT03012594: Lanreotide in the Treatment of Small Bowel Motility Disorders
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Motility Disorder
Intestinal Disease
Keywords: Small bowel motility disorder
Slow intestinal motility
Small bowel bacterial overgrowth
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2017-01-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill
timeFrame: 3 months
Secondary outcomes:
measure: Improvement in Symptoms as Accessed by "Patient Assessment of Upper GastroIntestinal Symptom Severity Index"
timeFrame: 3 months
Other outcomes:
Locations:
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
Study officials:
affiliation: Northwell Health
name: Larry Miller, M.D.
role: PRINCIPAL_INVESTIGATOR
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