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Lanreotide in the Treatment of Small Bowel Motility Disorders

Sponsor
Northwell Health (Other)
Overall Status
Completed
CT.gov ID
NCT03012594
Collaborator
Ipsen (Industry)
12
Enrollment
2
Locations
1
Arm
22
Actual Duration (Months)
6
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 11, 2017
Actual Primary Completion Date :
Oct 21, 2018
Actual Study Completion Date :
Mar 11, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lanreotide

Open label

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill [3 months]

      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.

    Secondary Outcome Measures

    1. Improvement in Symptoms as Accessed by "Patient Assessment of Upper GastroIntestinal Symptom Severity Index" [3 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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%)

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

    2. 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.

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

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

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

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

    5. Pancreatitis

    6. 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)

    7. Present cholecystitis

    8. Uncontrolled congestive heart failure

    9. Known hypersensitivity to the study drug

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    2 Lenox Hill Hospital New York New York United States 10075

    Sponsors and Collaborators

    • Northwell Health
    • Ipsen

    Investigators

    • Principal Investigator: Larry Miller, M.D., Northwell Health

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Larry Miller, Chief of Gastroenterology, Northwell Health
    ClinicalTrials.gov Identifier:
    NCT03012594
    Other Study ID Numbers:
    • HS16-0465
    First Posted:
    Jan 6, 2017
    Last Update Posted:
    Jan 15, 2021
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Larry Miller, Chief of Gastroenterology, Northwell Health
    Small bowel motility disorder
    Slow intestinal motility
    Small bowel bacterial overgrowth
    Additional relevant MeSH terms:
    Intestinal Diseases
    Disease
    Lanreotide

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail 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.
    Arm/Group Title Lanreotide
    Arm/Group Description 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
    Period Title: Overall Study
    STARTED 12
    COMPLETED 9
    NOT COMPLETED 3

    Baseline Characteristics

    Arm/Group Title Lanreotide
    Arm/Group Description 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
    Overall Participants 9
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    46.78
    (13.33)
    Sex: Female, Male (Count of Participants)
    Female
    7
    77.8%
    Male
    2
    22.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    22.2%
    Not Hispanic or Latino
    7
    77.8%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    22.2%
    White
    6
    66.7%
    More than one race
    0
    0%
    Unknown or Not Reported
    1
    11.1%
    Region of Enrollment (Number) [Number]
    United States
    9
    100%
    BMI (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    27.11
    (6.8)
    Heart rate (beats/sec) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [beats/sec]
    70.67
    (10.91)
    Systolic Blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    120
    (19)
    Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    77
    (8)
    Blood Glucose (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    118
    (75)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Heartburn/regurgitation (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.73
    (1.85)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Nausea/vomiting (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.85
    (2.07)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Fullness/early satiety (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    3.22
    (1.84)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Bloating (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    3.67
    (1.57)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Upper abdominal pain (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.5
    (1.86)
    Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Lower abdominal pain (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.83
    (1.62)
    Gastric emptying time (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    323
    (232)
    Small bowel transit time (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    505
    (159)
    Colonic transit time (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    2503
    (1592)
    Small bowel and colonic transit time (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    2835
    (1556)
    Whole gut transit time (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    3160
    (1533)
    Stomach Contractions (Contractions/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Contractions/min]
    2.06
    (1.02)
    Stomach Mean Pressure (mm Hg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm Hg]
    4.44
    (3.31)
    Stomach High Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    313.82
    (53.86)
    Stomach Low pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    0
    (3.84)
    Stomach Median pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    2.21
    (1.21)
    Stomach High pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    7.48
    (3.22)
    Gastric Antrum Motility Index (index) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [index]
    17.68
    (22.7)
    Antrum Contractions (Contractions/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Contractions/min]
    2.4
    (2.09)
    Antrum Mean Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    4.89
    (3.88)
    Antrum High Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    271.94
    (104.4)
    Antrum Low pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    0.76
    (0.49)
    Antrum Median pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    1.13
    (0.87)
    Antrum High pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    4.67
    (1.81)
    Duodenum Motility Index (index) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [index]
    16.84
    (22.36)
    Duodenum Contractions (Contractions/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Contractions/min]
    3.13
    (2.99)
    Duodenum Mean Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    3.52
    (1.85)
    Duodenum High Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    87.07
    (59.38)
    Duodenum Low pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    2.33
    (1.83)
    Duodenum Median pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    6.30
    (0.64)
    Duodenum High pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    7.07
    (0.60)
    Small Bowel Contractions (Contractions/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Contractions/min]
    3.88
    (2.05)
    Small Bowel Mean Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    4.03
    (1.71)
    Small Bowel High Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    143.67
    (88.35)
    Small Bowel Low pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    2.32
    (1.87)
    Small Bowel Median pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    7.36
    (0.15)
    Small Bowel High pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    7.89
    (0.30)
    Colon Contractions (Contractions/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Contractions/min]
    2.10
    (0.78)
    Colon Mean Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    4.29
    (1.21)
    Colon High Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    177.84
    (108.54)
    Colon Low pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    5.19
    (0.37)
    Colon Median pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    6.44
    (0.41)
    Colon High pH (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    8.41
    (0.38)

    Outcome Measures

    1. Primary Outcome
    Title Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill
    Description 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.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lanreotide
    Arm/Group Description 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
    Measure Participants 9
    Gastric emptying time
    371.52
    (45.18)
    Small bowel transit time
    392
    (47.51)
    Colonic transit time
    4767
    (1286)
    Small bowel and Colonic transit time
    5159
    (1284)
    Whole gut transit time
    5530
    (1322)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanreotide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.07
    Comments
    Method t-test, 2 sided
    Comments
    2. Secondary Outcome
    Title Improvement in Symptoms as Accessed by "Patient Assessment of Upper GastroIntestinal Symptom Severity Index"
    Description 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.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lanreotide
    Arm/Group Description 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
    Measure Participants 9
    Heartburn/regurgitation
    1.48
    (0.27)
    Nausea/vomiting
    1.00
    (0.35)
    Fullness/early satiety
    2.36
    (0.4)
    Bloating
    2.43
    (0.47)
    Upper abdominal pain
    2.14
    (0.62)
    Lower abdominal pain
    2.00
    (0.51)

    Adverse Events

    Time Frame 1 month after last dose, up to 4 months from the start for each subject.
    Adverse Event Reporting Description
    Arm/Group Title Lanreotide
    Arm/Group Description 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
    All Cause Mortality
    Lanreotide
    Affected / at Risk (%) # Events
    Total 0/9 (0%)
    Serious Adverse Events
    Lanreotide
    Affected / at Risk (%) # Events
    Total 0/9 (0%)
    Other (Not Including Serious) Adverse Events
    Lanreotide
    Affected / at Risk (%) # Events
    Total 2/9 (22.2%)
    Investigations
    Difficulty swallowing wireless motility capsule pill 1/9 (11.1%) 9
    Unable to acknowledge the passage of the wireless motility capsule through the feces 1/9 (11.1%) 9

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr.Larry Miller
    Organization Northwell health
    Phone 5165620334
    Email lmiller7@northwell.edu
    Responsible Party:
    Larry Miller, Chief of Gastroenterology, Northwell Health
    ClinicalTrials.gov Identifier:
    NCT03012594
    Other Study ID Numbers:
    • HS16-0465
    First Posted:
    Jan 6, 2017
    Last Update Posted:
    Jan 15, 2021
    Last Verified:
    Dec 1, 2020