Gastroparesis
Conditions
Brief summary
The Vibrant capsule is a novel vibrating device for the treatment of gastrointestinal disorders. The effect of different vibrations on the motor functions of the gastrointestinal tract are unclear. The study will focus on the stomach in healthy volunteers. The study will compare the effects of Vibrant capsule treatment and Sham capsule treatment on gastric emptying and gastric motility in healthy volunteers.
Detailed description
Healthy volunteers participants were randomized to one of 4 treatment groups: sham VIBRANT or vibrating VIBRANT capsule at rates of 1, 3 or 5 per minute. The studies were conducted in one day. Following an overnight fast, participants underwent introduction of the multilumen manometric catheter into the proximal small intestine with sensors across the antroduodenal junction. A 4-meter Teflon® (green) guidewire and manometry tube were placed transnasally and advanced into the duodenum with the distal end of the manometry tube within the distal duodenum or proximal jejunum. Following placement of the manometry tube a 30 minute baseline motility assessment was performed followed by the first of two VIBRANT OR SHAM VIBRANT CAPSULES administered as randomly assigned. Motility assessment performed for an additional 25-30 minutes before the digestion of the standardized breakfast test meal. A single spot image will be obtained to document the location of the capsule prior to the meal. Approximately thirty minutes following ingestion of the capsule, participants ingested a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. In addition, every 30 minutes one hundred millimeter Visual analog scales (VAS) recorded to assess levels of nausea, fullness, gas, and abdominal pain. Participants were seated in a semi-recumbent position (\ 45 degrees) for recording motility and obtaining anterior scintigraphy images simultaneously. Following the 90-minute scan, the participants ingested a second active VIBRANT or sham capsule. Subsequent scans continued at scheduled intervals until 240 minutes after the test meal ingestion to complete the assessment of gastric emptying.
Interventions
DEVICESham vibrating capsule
Sham device without vibration
DEVICEVibrant Capsule (1 vibration)
1 vibration/min
DEVICEVibrant Capsule (3 vibration)
3 vibration/min
DEVICEVibrant Capsule (5 vibration)
5 vibration/min
Sponsors
Vibrant Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able to provide written informed consent prior to any study procedures, and be willing and able to comply with study procedures 2. No medical problems or chronic diseases, specifically, no type 2 diabetes mellitus 3. Body mass index of 18-35 kg/m2 4. Female subjects must have negative urine pregnancy tests and must not be lactating prior to receiving study medication and radiation exposure. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. Female subjects unable to bear children must have this documented in the medical record \[i.e., tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)\].
Exclusion criteria
1. Unable or unwilling to provide informed consent or to comply with study procedures 2. Diagnosis of gastrointestinal diseases 3. Structural or metabolic diseases that affect the gastrointestinal system 4. Unable to avoid the following over-the-counter medications 48 hours prior to the baseline period and throughout the study: 1. Medications that alter gastrointestinal transit including laxatives, magnesium and aluminum containing antacids, prokinetics, erythromycin 2. Analgesic drugs including Nonsteroidal Anti-Inflammatory Drugs and COX-2 inhibitors NOTE: stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for cardioprotection, and birth control (but with adequate backup contraception as drug-interactions with birth control have not been conducted) are permissible. 5. History of recent surgery (within 60 days of screening) 6. Acute or chronic illness or history of illness which, in the opinion of the investigator, could pose a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation of study data, such as frequent angina, Class III or IV congestive heart failure, moderate impairment of renal or hepatic function, poorly controlled diabetes, etc. 7. Any clinically significant abnormalities on physical examination or laboratory abnormalities identified in the medical record, as determined by the investigator 8. Acute gastrointestinal illness within 48 hours of initiation of the baseline period 9. Females who are pregnant or breastfeeding 10. History of excessive alcohol use or substance abuse 11. Participation in an investigational study within the 30 days prior to dosing in the present study 12. Any other reason, which in the opinion of the investigator, would confound proper interpretation of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastroduodenal Manometry Measurement | 1 hour | The main outcome measure is the Gastro-duodenal manometry measurement of the first hour postprandial distal antral motility index (MI), which is calculated as: MI = loge (sum of amplitude x number of contractions + 1) every 15 minutes following postcibal period (60 min). Effect size is the difference between means as a percentage of the mean index between the treatment groups. Estimated effect sizes are based on a paired t-test with the expected difference in mean of 1.6 motility index units in distal antral activity or 13.6% change in the antral motility index in ACTIVE compared to SHAM. It is to be noted that this is on a logarithmic scale and, therefore, a 10% change constitutes a clinically relevant difference. A higher MI value represents a better outcome. |
| Gastric Emptying of Solids - T1/2 | 4 hours | The median solid gastric emptying half-time in minutes from the stomach after a mixed meal as measured by scintigraphy. Approximately thirty minutes following ingestion of the Vibarnt / sham capsule, subjects ingested a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Emptying at One Hour | 1 hour | Gastric emptying scintigraphy (GES) is the 'gold standard' measurement for assessing stomach emptying rate. Stomach emptying was measured following ingestion of a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. The outcome of GES at one hour is measuring the rate of solid emptying from the stomach after one hour in each of the study arms. A higher Fraction of solids emptying represents faster stomach emptying. |
| Gastric Emptying at Two Hours | 2 hours | Gastric emptying scintigraphy (GES) is the 'gold standard' measurement for assessing stomach emptying rate. Stomach emptying was measured following ingestion of a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. The outcome of GES at two hours is measuring the rate of solid emptying from the stomach after two hours in each of the study arms. A higher Fraction of solids emptying represents faster stomach emptying. |
| Postprandial Distal Antral Motility Index | 30 minutes | First 0.5h postprandial distal antral motility index (Gastroduodenal Motility index (MI) MI formula: MI = loge (sum of amplitude x number of contractions + 1). Effect size is the difference between means as a percentage of the mean index between the treatment groups. Estimated effect sizes are based on a paired t-test with expected difference in mean of 1.6 motility index units in distal antral activity or 13.6% change in the antral motility index in ACTIVE compared to SHAM. It is to be noted that this is on a logarithmic scale and, therefore, an 10% change constitutes a clinically relevant difference. A higher MI value represents a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Vibrating Capsule Sham vibrating capsule
Sham vibrating capsule: Sham device without vibration | 6 |
| Vibrant Capsule (1 Vibration) 1 vibration/min
Vibrant Capsule (1 vibration): 1 vibration/min | 6 |
| Vibrant Capsule (3 Vibration) 3 vibrations/min
Vibrant Capsule (3 vibration): 3 vibration/min | 6 |
| Vibrant Capsule (5 Vibration) 5 vibrations/min
Vibrant Capsule (5 vibration): 5 vibration/min | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | stopped study after receipt of Capsule #1 due to sore throat. | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Sham Vibrating Capsule | Vibrant Capsule (1 Vibration) | Vibrant Capsule (3 Vibration) | Vibrant Capsule (5 Vibration) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 15.8 | 38.17 years STANDARD_DEVIATION 18.05 | 28.5 years STANDARD_DEVIATION 10.82 | 28.17 years STANDARD_DEVIATION 10.26 | 32 years STANDARD_DEVIATION 13.89 |
| Body mass index (BMI) | 26.75 kg/m^2 STANDARD_DEVIATION 3.02 | 26.3 kg/m^2 STANDARD_DEVIATION 4.97 | 26.83 kg/m^2 STANDARD_DEVIATION 1.89 | 26.73 kg/m^2 STANDARD_DEVIATION 4.745 | 26.57 kg/m^2 STANDARD_DEVIATION 3.66 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Gastric Emptying of Solids - T1/2
The median solid gastric emptying half-time in minutes from the stomach after a mixed meal as measured by scintigraphy. Approximately thirty minutes following ingestion of the Vibarnt / sham capsule, subjects ingested a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes.
Time frame: 4 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Vibrating Capsule | Gastric Emptying of Solids - T1/2 | 120.7 Minutes | Standard Deviation 31.78 |
| Vibrant Capsule (1 Vibration) | Gastric Emptying of Solids - T1/2 | 132.3 Minutes | Standard Deviation 34.38 |
| Vibrant Capsule (3 Vibration) | Gastric Emptying of Solids - T1/2 | 134.7 Minutes | Standard Deviation 35.89 |
| Vibrant Capsule (5 Vibration) | Gastric Emptying of Solids - T1/2 | 132.2 Minutes | Standard Deviation 43.91 |
Primary
Gastroduodenal Manometry Measurement
The main outcome measure is the Gastro-duodenal manometry measurement of the first hour postprandial distal antral motility index (MI), which is calculated as: MI = loge (sum of amplitude x number of contractions + 1) every 15 minutes following postcibal period (60 min). Effect size is the difference between means as a percentage of the mean index between the treatment groups. Estimated effect sizes are based on a paired t-test with the expected difference in mean of 1.6 motility index units in distal antral activity or 13.6% change in the antral motility index in ACTIVE compared to SHAM. It is to be noted that this is on a logarithmic scale and, therefore, a 10% change constitutes a clinically relevant difference. A higher MI value represents a better outcome.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Vibrating Capsule | Gastroduodenal Manometry Measurement | 9.862 motility index units (see Description) | Standard Deviation 1.549 |
| Vibrant Capsule (1 Vibration) | Gastroduodenal Manometry Measurement | 10.38 motility index units (see Description) | Standard Deviation 0.864 |
| Vibrant Capsule (3 Vibration) | Gastroduodenal Manometry Measurement | 10.38 motility index units (see Description) | Standard Deviation 1.469 |
| Vibrant Capsule (5 Vibration) | Gastroduodenal Manometry Measurement | 8.433 motility index units (see Description) | Standard Deviation 3.38 |
Secondary
Gastric Emptying at One Hour
Gastric emptying scintigraphy (GES) is the 'gold standard' measurement for assessing stomach emptying rate. Stomach emptying was measured following ingestion of a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. The outcome of GES at one hour is measuring the rate of solid emptying from the stomach after one hour in each of the study arms. A higher Fraction of solids emptying represents faster stomach emptying.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Vibrating Capsule | Gastric Emptying at One Hour | 0.298 Fraction of solids emptying | Standard Deviation 0.0979 |
| Vibrant Capsule (1 Vibration) | Gastric Emptying at One Hour | 0.273 Fraction of solids emptying | Standard Deviation 0.0885 |
| Vibrant Capsule (3 Vibration) | Gastric Emptying at One Hour | 0.248 Fraction of solids emptying | Standard Deviation 0.0679 |
| Vibrant Capsule (5 Vibration) | Gastric Emptying at One Hour | 0.264 Fraction of solids emptying | Standard Deviation 0.0532 |
Secondary
Gastric Emptying at Two Hours
Gastric emptying scintigraphy (GES) is the 'gold standard' measurement for assessing stomach emptying rate. Stomach emptying was measured following ingestion of a standardized breakfast meal (320kcal egg, toast, milk) containing 99mTc. Anterior and posterior gamma camera images were obtained immediately following ingestion of the meal and every 15 minutes until 240 minutes. The outcome of GES at two hours is measuring the rate of solid emptying from the stomach after two hours in each of the study arms. A higher Fraction of solids emptying represents faster stomach emptying.
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Vibrating Capsule | Gastric Emptying at Two Hours | 0.495 Fraction of solids emptying | Standard Deviation 0.125 |
| Vibrant Capsule (1 Vibration) | Gastric Emptying at Two Hours | 0.485 Fraction of solids emptying | Standard Deviation 0.168 |
| Vibrant Capsule (3 Vibration) | Gastric Emptying at Two Hours | 0.457 Fraction of solids emptying | Standard Deviation 0.104 |
| Vibrant Capsule (5 Vibration) | Gastric Emptying at Two Hours | 0.498 Fraction of solids emptying | Standard Deviation 0.177 |
Secondary
Postprandial Distal Antral Motility Index
First 0.5h postprandial distal antral motility index (Gastroduodenal Motility index (MI) MI formula: MI = loge (sum of amplitude x number of contractions + 1). Effect size is the difference between means as a percentage of the mean index between the treatment groups. Estimated effect sizes are based on a paired t-test with expected difference in mean of 1.6 motility index units in distal antral activity or 13.6% change in the antral motility index in ACTIVE compared to SHAM. It is to be noted that this is on a logarithmic scale and, therefore, an 10% change constitutes a clinically relevant difference. A higher MI value represents a better outcome.
Time frame: 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Vibrating Capsule | Postprandial Distal Antral Motility Index | 10.3 motility index units (See Description) | Standard Deviation 1.102 |
| Vibrant Capsule (1 Vibration) | Postprandial Distal Antral Motility Index | 10.38 motility index units (See Description) | Standard Deviation 1.446 |
| Vibrant Capsule (3 Vibration) | Postprandial Distal Antral Motility Index | 10.55 motility index units (See Description) | Standard Deviation 1.532 |
| Vibrant Capsule (5 Vibration) | Postprandial Distal Antral Motility Index | 10.34 motility index units (See Description) | Standard Deviation 1.141 |