Gastroparesis
Conditions
Keywords
Nausea and Vomiting
Brief summary
This study is to evaluate the safety and effectiveness of gastric stimulation in the reduction of nausea and vomiting in patients with gastroparesis using an approved Humanitarian device. There are two cohorts in this study based on etiology, one for diabetic and one for idiopathic. A maximum of 150 patients (75 diabetic and 75 idiopathic) from up to 15 centers in the United States will be followed closely for twelve months and then once a year after that until the study closes. If you are someone suffering with symptoms of gastroparesis despite trying oral medications, you may be eligible to participate in a clinical study using a surgically implanted gastric stimulator.
Interventions
DEVICEEnterra Therapy
Gastric electrical stimulation using Enterra Therapy.
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or Female at least 18 years of age * Diagnosed with gastroparesis due to diabetes or an unknown cause (idiopathic) * Have tried prokinetic (help the stomach empty quicker) and antiemetic (help decrease symptoms of nausea and vomiting) medications for a minimum of one month, unless you're unable to take these types of medications * Have symptoms of gastroparesis that have required treatment for at least one year * Experience at least 7 episodes of vomiting during a seven consecutive day period on a 28-day diary * Willing and able to completely and accurately fill out a diary and questionnaires throughout the study * Have gastric retention of greater than 10% at four hours, or greater than 60% at two hours (if unable to complete the four-hour test) on a Gastric Emptying Test (GET)
Exclusion criteria
* Gastroparesis caused by a specific diagnosed illness other than diabetes * Current eating disorder or diagnosed swallowing disorder * Previous stomach surgeries * Taking narcotic pain-relievers daily for abdominal pain * Diagnosed with drug or alcohol dependency within 1 year before the study * Life expectancy less than one year * Have other implantable devices such as pacemakers * Pregnancy or planned pregnancy * Plan to receive diathermy treatment * Have had radiation therapy of the upper abdomen * Plan on having an MRI performed * Currently participating in another investigational device or drug study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Frequency of Weekly Vomiting Episodes When the Device is Turned ON, Relative to When the Device is Turned OFF | 4.5 months and 7.5 months | Diaries were used to record daily vomiting episodes for 28 days prior to each office follow-up visit. The weekly vomiting frequency (WVF) was based on the average number of weekly vomiting episodes recorded in the patient diary. The percent reduction is calculated as ((WVF during OFF - WVF during ON)/ (WVF during OFF))\*100%. A positive reduction represents an improvement in WVF when the device was ON. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Symptom Score When the Device is Turned ON, Relative to When the Device is Turned OFF | 4.5 months and 7.5 months | A symptom interview was conducted at each visit to assess vomiting, nausea, early satiety, bloating, postprandial fullness, epigastric pain and epigastric burning. The scale for each symptom ranges from 0 to 4, with 0 being absence of symptoms and 4 being extremely frequent (≥ 7 episodes per week). Total symptom score (TSS) is the sum of the individual frequency symptom scores. The percent reduction is calculated as ((TSS during OFF - TSS during ON)/ (TSS during OFF))\*100%. A positive reduction represents an improvement in TSS when the device was ON. |
| Percent Reduction in the Frequency of Weekly Vomiting Episodes at 12 Months Compared to Baseline | baseline and 12 months | Diaries were used to record daily vomiting episodes for 28 days prior to each office follow-up visit. The weekly vomiting frequency (WVF) was based on the average number of weekly vomiting episodes recorded in the patient diary. The percent reduction is calculated as ((WVF at baseline - WVF at 12 months)/ (WVF at baseline))\*100%. A positive reduction represents an improvement in WVF at 12 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life at 12 Months Compared to Baseline (Mental Component Summary) | baseline and 12 months | The QOL scores were collected using the SF-36 questionnaire, which included the scores in the following domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The mental component summary (MCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on mental health. The change in MCS is calculated as MCS at baseline - MCS at 12 months. A negative change in MCS represents an improvement in QOL. |
| Percentage of Responders at 12 Months | baseline and 12 months | Responders were defined as having a 50% or greater reduction of WVF from baseline to 12 months. The percentage of responders was estimated as the proportion of the responders among all subjects who finished the 12-month visit. The percentage of responders was tested to determine if it was statistically greater than 50%. |
| Change in Gastric Emptying Results at 12 Months Compared to Baseline (4 Hours) | baseline and 12 months | Gastric emptying was evaluated using a standardized scintigraphy method and a low fat egg substitute test meal. After standard meal and marker preparation, the subsequent images were taken at 2 hours and 4 hours and percentage of gastric retention was evaluated. Change in 4-hour GET is calculated as % of gastric retention at 4 hours at baseline - % of gastric retention at 4 hours at 12 months. A positive change represents an improvement in gastric emptying at 12 months. |
| Change in Gastric Emptying Results at 12 Months Compared to Baseline (2 Hours) | baseline and 12 months | Gastric emptying was evaluated using a standardized scintigraphy method and a low fat egg substitute test meal. After standard meal and marker preparation, the subsequent images were taken at 2 hours and 4 hours and percentage of gastric retention was evaluated. Change in 2-hour GET is calculated as % of gastric retention at 2 hours at baseline - % of gastric retention at 2 hours at 12 months. A positive change represents an improvement in gastric emptying at 12 months. |
| Change in Symptom Score at 12 Months Compared to Baseline. | baseline and 12 months | A symptom interview was conducted at each visit to assess vomiting, nausea, early satiety, bloating, postprandial fullness, epigastric pain and epigastric burning. The scale for each symptom ranges from 0 to 4, with 0 being absence of symptoms and 4 being extremely frequent (≥ 7 episodes per week). Total symptom score (TSS) is the sum of the individual frequency symptom scores. The change is calculated as TSS at baseline - TSS at 12 months. A positive change represents an improvement in TSS at 12 months. |
| Change in Quality of Life (QOL) at 12 Months Compared to Baseline (Physical Component Summary) | baseline and 12 months | The QOL scores were collected using the SF-36 questionnaire, which included the scores in the following domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The physical component summary (PCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on physical health. The change in PCS is calculated as PCS at baseline - PCS at 12 months. A negative change in PCS represents an improvement in QOL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diabetic This group contains all subjects that were enrolled and analyzed as part of the diabetic cohort. | 55 |
| Idiopathic This group contains all subjects that were enrolled and analyzed as part of the idiopathic cohort. | 32 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 3 | 2 | 0 | 0 |
| Overall Study | Explant due to infection | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Medical reason | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Study completion | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Study site closure | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Subject non-compliance | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Idiopathic | Total | Diabetic |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 87 Participants | 55 Participants |
| Age Continuous | 39.4 years STANDARD_DEVIATION 10.4 | 38.7 years STANDARD_DEVIATION 10 | 38.3 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 32 participants | 87 participants | 55 participants |
| Sex: Female, Male Female | 26 Participants | 62 Participants | 36 Participants |
| Sex: Female, Male Male | 6 Participants | 25 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 55 | 9 / 32 |
| serious Total, serious adverse events | 8 / 55 | 4 / 32 |
Outcome results
Primary
Percent Reduction in Frequency of Weekly Vomiting Episodes When the Device is Turned ON, Relative to When the Device is Turned OFF
Diaries were used to record daily vomiting episodes for 28 days prior to each office follow-up visit. The weekly vomiting frequency (WVF) was based on the average number of weekly vomiting episodes recorded in the patient diary. The percent reduction is calculated as ((WVF during OFF - WVF during ON)/ (WVF during OFF))\*100%. A positive reduction represents an improvement in WVF when the device was ON.
Time frame: 4.5 months and 7.5 months
Population: The analysis population included subjects who were randomized, completed the study through the end of the blinded crossover period and provided evaluable measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diabetic | Percent Reduction in Frequency of Weekly Vomiting Episodes When the Device is Turned ON, Relative to When the Device is Turned OFF | 0 percent reduction in WVF |
| Idiopathic | Percent Reduction in Frequency of Weekly Vomiting Episodes When the Device is Turned ON, Relative to When the Device is Turned OFF | 17.3 percent reduction in WVF |
Comparison: Null hypothesis: There was no change in the frequency of weekly vomiting episodes from when stimulation was turned OFF to when stimulation was turned ON, µ = 0;~Alternative hypothesis: There was a change in frequency of weekly vomiting episodes from when stimulation was turned OFF to when stimulation was turned ON, µ ≠ 0p-value: 0.215Wilcoxon Signed Rank Test
Comparison: Null hypothesis: There was no change in the frequency of weekly vomiting episodes from when stimulation was turned OFF to when stimulation was turned ON, µ = 0;~Alternative hypothesis: There was a change in frequency of weekly vomiting episodes from when stimulation was turned OFF to when stimulation was turned ON, µ ≠ 0p-value: 1Wilcoxon Signed Rank Test
Secondary
Percent Reduction in Symptom Score When the Device is Turned ON, Relative to When the Device is Turned OFF
A symptom interview was conducted at each visit to assess vomiting, nausea, early satiety, bloating, postprandial fullness, epigastric pain and epigastric burning. The scale for each symptom ranges from 0 to 4, with 0 being absence of symptoms and 4 being extremely frequent (≥ 7 episodes per week). Total symptom score (TSS) is the sum of the individual frequency symptom scores. The percent reduction is calculated as ((TSS during OFF - TSS during ON)/ (TSS during OFF))\*100%. A positive reduction represents an improvement in TSS when the device was ON.
Time frame: 4.5 months and 7.5 months
Population: The analysis population included subjects who were randomized, completed the study through the end of the blinded crossover period and provided evaluable measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diabetic | Percent Reduction in Symptom Score When the Device is Turned ON, Relative to When the Device is Turned OFF | 0 Percent reduction in symptom score |
| Idiopathic | Percent Reduction in Symptom Score When the Device is Turned ON, Relative to When the Device is Turned OFF | 0 Percent reduction in symptom score |
Comparison: Null hypothesis: There was no change in total symptom score from when stimulation was turned OFF to when stimulation was turned ON, µ = 0;~Alternative hypothesis: There was a change in total symptom score from when stimulation was turned OFF to when stimulation was turned ON, µ ≠ 0p-value: 0.903Wilcoxon Signed Rank Test
Comparison: Null hypothesis: There was no change in total symptom score from when stimulation was turned OFF to when stimulation was turned ON, µ = 0;~Alternative hypothesis: There was a change in total symptom score from when stimulation was turned OFF to when stimulation was turned ON, µ ≠ 0p-value: 0.932Wilcoxon Signed Rank Test
Secondary
Percent Reduction in the Frequency of Weekly Vomiting Episodes at 12 Months Compared to Baseline
Diaries were used to record daily vomiting episodes for 28 days prior to each office follow-up visit. The weekly vomiting frequency (WVF) was based on the average number of weekly vomiting episodes recorded in the patient diary. The percent reduction is calculated as ((WVF at baseline - WVF at 12 months)/ (WVF at baseline))\*100%. A positive reduction represents an improvement in WVF at 12 months.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized, completed the study at 12 months and provided evaluable measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diabetic | Percent Reduction in the Frequency of Weekly Vomiting Episodes at 12 Months Compared to Baseline | 67.8 Percent reduction in WVF |
| Idiopathic | Percent Reduction in the Frequency of Weekly Vomiting Episodes at 12 Months Compared to Baseline | 87.1 Percent reduction in WVF |
Comparison: Null hypothesis: There was no change from baseline in the long-term frequency of weekly vomiting episodes, µ = 0;~Alternative hypothesis: There was a change from baseline in the long-term frequency of weekly vomiting episodes, µ ≠ 0p-value: <0.001Wilcoxon Signed Rank Test
Comparison: Null hypothesis: There was no change from baseline in the long-term frequency of weekly vomiting episodes, µ = 0;~Alternative hypothesis: There was a change from baseline in the long-term frequency of weekly vomiting episodes, µ ≠ 0p-value: <0.001Wilcoxon Signed Rank Test
Other Pre-specified
Change in Gastric Emptying Results at 12 Months Compared to Baseline (2 Hours)
Gastric emptying was evaluated using a standardized scintigraphy method and a low fat egg substitute test meal. After standard meal and marker preparation, the subsequent images were taken at 2 hours and 4 hours and percentage of gastric retention was evaluated. Change in 2-hour GET is calculated as % of gastric retention at 2 hours at baseline - % of gastric retention at 2 hours at 12 months. A positive change represents an improvement in gastric emptying at 12 months.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized, completed the study at 12 months and provided evaluable measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diabetic | Change in Gastric Emptying Results at 12 Months Compared to Baseline (2 Hours) | 18 Percent retention |
| Idiopathic | Change in Gastric Emptying Results at 12 Months Compared to Baseline (2 Hours) | 17.5 Percent retention |
Comparison: Null hypothesis: There was no change in 2-hour gastric emptying from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in 2-hour gastric emptying from baseline to 12 months, µ ≠ 0p-value: <0.001Wilcoxon Signed Rank Test
Comparison: Null hypothesis: There was no change in 2-hour gastric emptying from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in 2-hour gastric emptying from baseline to 12 months, µ ≠ 0p-value: <0.001Wilcoxon Signed Rank Test
Other Pre-specified
Change in Gastric Emptying Results at 12 Months Compared to Baseline (4 Hours)
Gastric emptying was evaluated using a standardized scintigraphy method and a low fat egg substitute test meal. After standard meal and marker preparation, the subsequent images were taken at 2 hours and 4 hours and percentage of gastric retention was evaluated. Change in 4-hour GET is calculated as % of gastric retention at 4 hours at baseline - % of gastric retention at 4 hours at 12 months. A positive change represents an improvement in gastric emptying at 12 months.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized, completed the study at 12 months and provided evaluable measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diabetic | Change in Gastric Emptying Results at 12 Months Compared to Baseline (4 Hours) | 22 Percent retention |
| Idiopathic | Change in Gastric Emptying Results at 12 Months Compared to Baseline (4 Hours) | 13.5 Percent retention |
Comparison: Null hypothesis: There was no change in 4-hour gastric emptying from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in 4-hour gastric emptying from baseline to 12 months, µ ≠ 0p-value: 0.016Wilcoxon Signed Rank Test
Comparison: Null hypothesis: There was no change in 4-hour gastric emptying from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in 4-hour gastric emptying from baseline to 12 months, µ ≠ 0p-value: 0.236Wilcoxon Signed Rank Test
Other Pre-specified
Change in Quality of Life at 12 Months Compared to Baseline (Mental Component Summary)
The QOL scores were collected using the SF-36 questionnaire, which included the scores in the following domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The mental component summary (MCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on mental health. The change in MCS is calculated as MCS at baseline - MCS at 12 months. A negative change in MCS represents an improvement in QOL.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized and completed the study at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diabetic | Change in Quality of Life at 12 Months Compared to Baseline (Mental Component Summary) | -6.81 Scores on a scale | Standard Deviation 15.15 |
| Idiopathic | Change in Quality of Life at 12 Months Compared to Baseline (Mental Component Summary) | -7.15 Scores on a scale | Standard Deviation 7.75 |
Comparison: Null hypothesis: There was no change in MCS score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in MCS score from baseline to 12 months, µ ≠ 0p-value: 0.009Paired t-test
Comparison: Null hypothesis: There was no change in MCS score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in MCS score from baseline to 12 months, µ ≠ 0p-value: 0.001Paired t-test
Other Pre-specified
Change in Quality of Life (QOL) at 12 Months Compared to Baseline (Physical Component Summary)
The QOL scores were collected using the SF-36 questionnaire, which included the scores in the following domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The physical component summary (PCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on physical health. The change in PCS is calculated as PCS at baseline - PCS at 12 months. A negative change in PCS represents an improvement in QOL.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized and completed the study at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diabetic | Change in Quality of Life (QOL) at 12 Months Compared to Baseline (Physical Component Summary) | -6.9 Scores on a scale | Standard Deviation 8.97 |
| Idiopathic | Change in Quality of Life (QOL) at 12 Months Compared to Baseline (Physical Component Summary) | -5.2 Scores on a scale | Standard Deviation 10.43 |
Comparison: Null hypothesis: There was no change in PCS score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in PCS score from baseline to 12 months, µ ≠ 0p-value: <0.001Paired t-test
Comparison: Null hypothesis: There was no change in PCS score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in PCS score from baseline to 12 months, µ ≠ 0p-value: 0.043Paired t-test
Other Pre-specified
Change in Symptom Score at 12 Months Compared to Baseline.
A symptom interview was conducted at each visit to assess vomiting, nausea, early satiety, bloating, postprandial fullness, epigastric pain and epigastric burning. The scale for each symptom ranges from 0 to 4, with 0 being absence of symptoms and 4 being extremely frequent (≥ 7 episodes per week). Total symptom score (TSS) is the sum of the individual frequency symptom scores. The change is calculated as TSS at baseline - TSS at 12 months. A positive change represents an improvement in TSS at 12 months.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized and completed the study at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diabetic | Change in Symptom Score at 12 Months Compared to Baseline. | 6.79 Scores on a scale | Standard Deviation 8.05 |
| Idiopathic | Change in Symptom Score at 12 Months Compared to Baseline. | 8.74 Scores on a scale | Standard Deviation 7.46 |
Comparison: Null hypothesis: There was no change in total symptom score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in total symptom score from baseline to 12 months, µ ≠ 0p-value: <0.001Paired t-test
Comparison: Null hypothesis: There was no change in total symptom score from baseline to 12 months, µ = 0;~Alternative hypothesis: There was a change in total symptom score from baseline to 12 months, µ ≠ 0p-value: <0.001Paired t-test
Other Pre-specified
Percentage of Responders at 12 Months
Responders were defined as having a 50% or greater reduction of WVF from baseline to 12 months. The percentage of responders was estimated as the proportion of the responders among all subjects who finished the 12-month visit. The percentage of responders was tested to determine if it was statistically greater than 50%.
Time frame: baseline and 12 months
Population: The analysis population included subjects who were randomized, completed the study at 12 months and provided evaluable measurements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic | Percentage of Responders at 12 Months | 69 Percentage of responders |
| Idiopathic | Percentage of Responders at 12 Months | 94 Percentage of responders |
Comparison: Null hypothesis: The percentage of responders was less than or equal to 50%;~Alternative hypothesis: The percentage of responders was greater than 50%p-value: 0.014binomial, 1 sided
Comparison: Null hypothesis: The percentage of responders was less than or equal to 50%;~Alternative hypothesis: The percentage of responders was greater than 50%p-value: <0.001binomial, 1 sided