Gastrointestinal Motility Disorder, Intestinal Disease
Conditions
Keywords
Small bowel motility disorder, Slow intestinal motility, Small bowel bacterial overgrowth
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.
Interventions
DRUGLanreotide
Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart
Sponsors
Ipsen
Northwell Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Lanreotide |
|---|---|
| Age, Continuous | 46.78 years STANDARD_DEVIATION 13.33 |
| Antrum Contractions | 2.4 Contractions/min STANDARD_DEVIATION 2.09 |
| Antrum High pH | 4.67 pH STANDARD_DEVIATION 1.81 |
| Antrum High Pressure | 271.94 mmHg STANDARD_DEVIATION 104.4 |
| Antrum Low pH | 0.76 pH STANDARD_DEVIATION 0.49 |
| Antrum Mean Pressure | 4.89 mmHg STANDARD_DEVIATION 3.88 |
| Antrum Median pH | 1.13 pH STANDARD_DEVIATION 0.87 |
| Blood Glucose | 118 mg/dL STANDARD_DEVIATION 75 |
| BMI | 27.11 kg/m^2 STANDARD_DEVIATION 6.8 |
| Colon Contractions | 2.10 Contractions/min STANDARD_DEVIATION 0.78 |
| Colon High pH | 8.41 pH STANDARD_DEVIATION 0.38 |
| Colon High Pressure | 177.84 mmHg STANDARD_DEVIATION 108.54 |
| Colonic transit time | 2503 minutes STANDARD_DEVIATION 1592 |
| Colon Low pH | 5.19 pH STANDARD_DEVIATION 0.37 |
| Colon Mean Pressure | 4.29 mmHg STANDARD_DEVIATION 1.21 |
| Colon Median pH | 6.44 pH STANDARD_DEVIATION 0.41 |
| Diastolic blood pressure | 77 mmHg STANDARD_DEVIATION 8 |
| Duodenum Contractions | 3.13 Contractions/min STANDARD_DEVIATION 2.99 |
| Duodenum High pH | 7.07 pH STANDARD_DEVIATION 0.6 |
| Duodenum High Pressure | 87.07 mmHg STANDARD_DEVIATION 59.38 |
| Duodenum Low pH | 2.33 pH STANDARD_DEVIATION 1.83 |
| Duodenum Mean Pressure | 3.52 mmHg STANDARD_DEVIATION 1.85 |
| Duodenum Median pH | 6.30 pH STANDARD_DEVIATION 0.64 |
| Duodenum Motility Index | 16.84 index STANDARD_DEVIATION 22.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gastric Antrum Motility Index | 17.68 index STANDARD_DEVIATION 22.7 |
| Gastric emptying time | 323 minutes STANDARD_DEVIATION 232 |
| Heart rate | 70.67 beats/sec STANDARD_DEVIATION 10.91 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Bloating | 3.67 units on a scale STANDARD_DEVIATION 1.57 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Fullness/early satiety | 3.22 units on a scale STANDARD_DEVIATION 1.84 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Heartburn/regurgitation | 1.73 units on a scale STANDARD_DEVIATION 1.85 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Lower abdominal pain | 2.83 units on a scale STANDARD_DEVIATION 1.62 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Nausea/vomiting | 1.85 units on a scale STANDARD_DEVIATION 2.07 |
| Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index_Upper abdominal pain | 2.5 units on a scale STANDARD_DEVIATION 1.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 9 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 2 Participants |
| Small bowel and colonic transit time | 2835 minutes STANDARD_DEVIATION 1556 |
| Small Bowel Contractions | 3.88 Contractions/min STANDARD_DEVIATION 2.05 |
| Small Bowel High pH | 7.89 pH STANDARD_DEVIATION 0.3 |
| Small Bowel High Pressure | 143.67 mmHg STANDARD_DEVIATION 88.35 |
| Small Bowel Low pH | 2.32 pH STANDARD_DEVIATION 1.87 |
| Small Bowel Mean Pressure | 4.03 mmHg STANDARD_DEVIATION 1.71 |
| Small Bowel Median pH | 7.36 pH STANDARD_DEVIATION 0.15 |
| Small bowel transit time | 505 minutes STANDARD_DEVIATION 159 |
| Stomach Contractions | 2.06 Contractions/min STANDARD_DEVIATION 1.02 |
| Stomach High pH | 7.48 pH STANDARD_DEVIATION 3.22 |
| Stomach High Pressure | 313.82 mmHg STANDARD_DEVIATION 53.86 |
| Stomach Low pH | 0 pH STANDARD_DEVIATION 3.84 |
| Stomach Mean Pressure | 4.44 mm Hg STANDARD_DEVIATION 3.31 |
| Stomach Median pH | 2.21 pH STANDARD_DEVIATION 1.21 |
| Systolic Blood pressure | 120 mmHg STANDARD_DEVIATION 19 |
| Whole gut transit time | 3160 minutes STANDARD_DEVIATION 1533 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 2 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanreotide | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | Small bowel and Colonic transit time | 5159 minutes | Standard Error 1284 |
| Lanreotide | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | Whole gut transit time | 5530 minutes | Standard Error 1322 |
| Lanreotide | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | Gastric emptying time | 371.52 minutes | Standard Error 45.18 |
| Lanreotide | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | Small bowel transit time | 392 minutes | Standard Error 47.51 |
| Lanreotide | Effect of Lanreotide on Gastrointestinal Motility as Measured by Smart Pill | Colonic transit time | 4767 minutes | Standard Error 1286 |
p-value: 0.07t-test, 2 sided
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Heartburn/regurgitation | 1.48 score on a scale | Standard Error 0.27 |
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Nausea/vomiting | 1.00 score on a scale | Standard Error 0.35 |
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Fullness/early satiety | 2.36 score on a scale | Standard Error 0.4 |
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Bloating | 2.43 score on a scale | Standard Error 0.47 |
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Upper abdominal pain | 2.14 score on a scale | Standard Error 0.62 |
| Lanreotide | Improvement in Symptoms as Accessed by Patient Assessment of Upper GastroIntestinal Symptom Severity Index | Lower abdominal pain | 2.00 score on a scale | Standard Error 0.51 |