Diabetic Gastroparesis
Conditions
Keywords
Diabetes, Gastroparesis
Brief summary
A pilot study to assess the safety, feasibility, and potential (uncontrolled) efficacy of continuous glucose monitoring (CGMS) in conjunction with an insulin pump to improve glycemic control for treatment of type 1 and type 2 diabetic patients with gastroparesis
Detailed description
This multicenter, uncontrolled, open label treatment study is to assess the safety of CGMS in guiding insulin pump therapy for 24 weeks by measuring mild, moderate, and severe hypoglycemic episodes in patients with type 1 and type 2 diabetes and gastroparesis.
Interventions
DEVICECGMS and insulin pump
Use of continuous glucose monitoring system and insulin pump
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Johns Hopkins Bloomberg School of Public 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
* Age 18 - 70 years old at registration * Type 1 or Type 2 diabetes mellitus for at least 2 years * Symptoms of gastroparesis (nausea, vomiting, early satiety, bloating, fullness, discomfort) for at least 1 year prior to registration * Gastroparesis Cardinal Symptom Index (GCSI) score of 18 * Delayed gastric emptying on gastric scintigraphy within 1 year of registration, defined as greater than 60% retention at 2 hours or greater than 10% retention at 4 hours * Hemoglobin A1c of at least 8.0% at registration regardless of current therapy. Individuals already receiving diabetes therapy via an insulin pump will be eligible for study participation if, in the opinion of the investigators, he/she may acquire additional benefit from continuous glucose monitoring that might improve glycemic control * Normal upper endoscopy within 1 year of registration * No clinical or imaging evidence of obstruction * Successful mastering of use of CGMS during the run-in period
Exclusion criteria
* Prior gastric surgery including fundoplication * Other systemic disease potentially causative of gastrointestinal symptoms * Acute or chronic renal insufficiency with creatinine \>1.5 mg/dL * Psychiatric disease or eating disorder * Pregnancy * Any other condition which, in the opinion of the investigators, would impede compliance or hinder completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemic Episodes | 4 weeks screening vs 24 weeks follow-up | The incidence rate (events / person-week) of mild/moderate (glucose level \< 70 mg/dL) and severe (glucose \< 50 mg/dL) hypoglycemic episodes during screening vs 24 week of follow-up visits while using a combination of continuous glucose monitoring system (CGMS) and insulin pump therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change from baseline (screening) vs 24 weeks of follow-up | To determine the efficacy of CGMS guided insulin pump therapy on symptoms of gastroparesis as assessed by GCSI total score and mean score and quality of life as assessed by PAGI-QOL score in diabetics with gastroparesis. The outcome is assessed using the self-reported total GCSI score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item postprandial fullness/early satiety subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. The self-reported PAGI-QOL total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected in the last 2 weeks.The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks. |
Countries
United States
Participant flow
Recruitment details
Forty-five patients (age 18-70 years) with diabetes for \>2 years in poor glycemic control (HbA1c \>8%) with gastroparesis were recruited from 7 centers of the GpCRC from February 2012 through May 2014. Patients had symptoms for \>1 year with Gastroparesis Cardinal Symptom Index (GCSI) scores of ≥18.
Pre-assignment details
Screening Phase-Baseline glycemic profiles were obtained with blinded sensors to acquire \>216 hours of glycemic data over 2 weeks. Run-In Phase:Participants received detailed instructions in operating the CSII device and had to demonstrate competency in CSII and CGM and electronic CGM data transfer to be enrolled.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Continuous glucose monitoring in conjunction with insulin pump
CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| 2 hr gastric retention | 63 percentage STANDARD_DEVIATION 20 |
| 4 hr gastric retention | 32 percentage STANDARD_DEVIATION 20 |
| Age, Continuous | 45 years STANDARD_DEVIATION 12 |
| Body mass index | 29 kg/m^2 STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| GCSI score | 3.3 units on a scale STANDARD_DEVIATION 0.8 |
| Hemoglobin A1c | 9.4 percentage STANDARD_DEVIATION 1.4 |
| Known diabetes duration | 21 years STANDARD_DEVIATION 11 |
| PAGI-QOL | 2.4 units on a scale STANDARD_DEVIATION 1.1 |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 14 Participants |
| Volume consumed in a liquid nutrient satiety test | 420 mL STANDARD_DEVIATION 258 |
| Volume of Water consumed for water load satiety test | 430 mL STANDARD_DEVIATION 207 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 45 |
| serious Total, serious adverse events | 16 / 45 |
Outcome results
Primary
Hypoglycemic Episodes
The incidence rate (events / person-week) of mild/moderate (glucose level \< 70 mg/dL) and severe (glucose \< 50 mg/dL) hypoglycemic episodes during screening vs 24 week of follow-up visits while using a combination of continuous glucose monitoring system (CGMS) and insulin pump therapy.
Time frame: 4 weeks screening vs 24 weeks follow-up
Population: 44 patients had non-missing data during screening phase and 37 had non-missing data during treatment phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Hypoglycemic Episodes | Screening phase, hypoglycemia / person-week | 1.9 event rate per person-week |
| All Participants | Hypoglycemic Episodes | Treatment phase, hypoglycemia / person-week | 2.2 event rate per person-week |
Comparison: Null hypothesis: Difference of 0% in the frequencies of hypoglycemic excursions (\<50 mg/dL) during the screening phase and treatment phase respectively.p-value: <0.0001Regression, Logistic
Comparison: Null hypothesis: Difference of 0% in the frequencies of hypoglycemic excursions (\<70 mg/dL) during the screening phase and treatment phase respectively.p-value: <0.0001Regression, Logistic
Comparison: Null hypothesis: Difference of 0% in the frequencies of euglycemic excursions (70-180 mg/dL) during the screening phase and treatment phase respectively.p-value: 0.005Regression, Logistic
Comparison: Null hypothesis: Difference of 0% in the frequencies of hyperglycemic excursions (\>180 mg/dL) during the screening phase and treatment phase respectively.p-value: 0.04Regression, Logistic
Comparison: Null hypothesis: Difference of 0% in the frequencies of hyperglycemic excursions (\>300 mg/dL) during the screening phase and treatment phase respectively.p-value: <0.0001Regression, Logistic
Secondary
Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score
To determine the efficacy of CGMS guided insulin pump therapy on symptoms of gastroparesis as assessed by GCSI total score and mean score and quality of life as assessed by PAGI-QOL score in diabetics with gastroparesis. The outcome is assessed using the self-reported total GCSI score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item postprandial fullness/early satiety subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. The self-reported PAGI-QOL total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected in the last 2 weeks.The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks.
Time frame: Change from baseline (screening) vs 24 weeks of follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in total GCSI score, screening to 12 weeks | -7.2 score on a scale | Standard Deviation 8.2 |
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in total GCSI score, screening to 24 weeks | -7.1 score on a scale | Standard Deviation 9.1 |
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in GCSI composite, screening to 12 weeks | -0.6 score on a scale | Standard Deviation 0.9 |
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in GCSI composite, screening to 24 weeks | -0.8 score on a scale | Standard Deviation 1 |
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in PAGI-QOL score, screening to 12 weeks | 0.7 score on a scale | Standard Deviation 0.9 |
| All Participants | Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score | Change in PAGI-QOL score, screening to 24 weeks | 0.7 score on a scale | Standard Deviation 0.9 |
Comparison: Null hypothesis: No difference in total GCSI score from screening to 12 weeks of treatment.p-value: <0.0001paired t-test
Comparison: Null hypothesis: No difference in total GCSI score from screening to 24 weeks of treatment.p-value: <0.0001paired t-test
Comparison: Null hypothesis: No difference in GCSI composite score from screening to 12 weeks of treatment.p-value: <0.0001paired t-test
Comparison: Null hypothesis: No difference in GCSI composite score from screening to 24 weeks of treatment.p-value: <0.0001paired t-test
Comparison: Null hypothesis: No difference in PAGI-QOL score from screening to 12 weeks of treatment.p-value: <0.0001paired t-test
Comparison: Null hypothesis: No difference in PAGI-QOL score from screening to 24 weeks of treatment.p-value: <0.0001paired t-test