GLUMIT-DG: Continuous Glucose Monitoring and Insulin Pump Therapy in Diabetic Gastroparesis

Sponsor
Johns Hopkins Bloomberg School of Public Health (Other)
Overall Status
Completed
CT.gov ID
NCT01030341
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
45
7
1
44.1
6.4
0.1

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Device: CGMS and insulin pump
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pilot Study of the Safety, Feasibility, and Potential Efficacy of Continuous Glucose Monitoring and Insulin Pump Therapy in Diabetic Gastroparesis (GLUMIT-DG)
Study Start Date :
May 1, 2011
Actual Primary Completion Date :
Nov 1, 2014
Actual Study Completion Date :
Jan 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: CGMS and insulin pump

Continuous glucose monitoring in conjunction with insulin pump

Device: CGMS and insulin pump
Use of continuous glucose monitoring system and insulin pump
Other Names:
  • Paradigm 722 Insulin pump
  • Real-Time Continuous Glucose Monitoring System
  • Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 California Pacific Medical Center San Francisco California United States 94115
    2 Stanford University Stanford California United States 94305-5187
    3 University of Michigan Medical Center Ann Arbor Michigan United States 48109
    4 University of Mississippi Medical Center Jackson Mississippi United States 39216
    5 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    6 Temple University Hospital Philadelphia Pennsylvania United States 19140
    7 Texas Tech University Health Sciences Center El Paso Texas United States 79905

    Sponsors and Collaborators

    • Johns Hopkins Bloomberg School of Public Health
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

    • Study Director: Frank Hamilton, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Johns Hopkins Bloomberg School of Public Health
    ClinicalTrials.gov Identifier:
    NCT01030341
    Other Study ID Numbers:
    • U01DK074008 GLUMIT-DG
    • U01DK073983
    • U01DK073975
    • U01DK073985
    • U01DK074035
    • U01DK074008
    • U01DK073974
    • U01DK074007
    First Posted:
    Dec 11, 2009
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Johns Hopkins Bloomberg School of Public Health
    Additional relevant MeSH terms:

    Study Results

    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 Detail 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.
    Arm/Group Title All Participants
    Arm/Group Description Continuous glucose monitoring in conjunction with insulin pump CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump
    Period Title: Overall Study
    STARTED 45
    COMPLETED 42
    NOT COMPLETED 3

    Baseline Characteristics

    Arm/Group Title All Participants
    Arm/Group Description Continuous glucose monitoring in conjunction with insulin pump CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump
    Overall Participants 45
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    45
    (12)
    Sex: Female, Male (Count of Participants)
    Female
    31
    68.9%
    Male
    14
    31.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    11
    24.4%
    Not Hispanic or Latino
    34
    75.6%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    45
    100%
    Known diabetes duration (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    21
    (11)
    Body mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    29
    (8)
    Hemoglobin A1c (percentage) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage]
    9.4
    (1.4)
    2 hr gastric retention (percentage) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage]
    63
    (20)
    4 hr gastric retention (percentage) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage]
    32
    (20)
    GCSI score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    3.3
    (0.8)
    PAGI-QOL (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.4
    (1.1)
    Volume of Water consumed for water load satiety test (mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL]
    430
    (207)
    Volume consumed in a liquid nutrient satiety test (mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL]
    420
    (258)

    Outcome Measures

    1. Primary Outcome
    Title Hypoglycemic Episodes
    Description 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

    Outcome Measure Data

    Analysis Population Description
    44 patients had non-missing data during screening phase and 37 had non-missing data during treatment phase
    Arm/Group Title All Participants
    Arm/Group Description Continuous glucose monitoring in conjunction with insulin pump CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump
    Measure Participants 44
    Screening phase, hypoglycemia / person-week
    1.9
    Treatment phase, hypoglycemia / person-week
    2.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: Difference of 0% in the frequencies of hypoglycemic excursions (<50 mg/dL) during the screening phase and treatment phase respectively.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Type I error: 0.05; power: 0.9
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Threshold for statistical significance: p < 0.05
    Method Regression, Logistic
    Comments Generalized estimating equations (GEE) with independent working correlation to account for correlated data comparing screening and treatment phases
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: Difference of 0% in the frequencies of hypoglycemic excursions (<70 mg/dL) during the screening phase and treatment phase respectively.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Type I error: 0.05; power: 0.9
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Threshold for statistical significance: p < 0.05
    Method Regression, Logistic
    Comments Generalized estimating equations (GEE) with independent working correlation to account for correlated data comparing screening and treatment phases
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: Difference of 0% in the frequencies of euglycemic excursions (70-180 mg/dL) during the screening phase and treatment phase respectively.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Type I error: 0.05; power: 0.9
    Statistical Test of Hypothesis p-Value 0.005
    Comments Threshold for statistical significance: p < 0.05
    Method Regression, Logistic
    Comments Generalized estimating equations (GEE) with independent working correlation to account for correlated data comparing screening and treatment phases
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: Difference of 0% in the frequencies of hyperglycemic excursions (>180 mg/dL) during the screening phase and treatment phase respectively.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Type I error: 0.05; power: 0.9
    Statistical Test of Hypothesis p-Value 0.04
    Comments Threshold for statistical significance: p < 0.05
    Method Regression, Logistic
    Comments Generalized estimating equations (GEE) with independent working correlation to account for correlated data comparing screening and treatment phases
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: Difference of 0% in the frequencies of hyperglycemic excursions (>300 mg/dL) during the screening phase and treatment phase respectively.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Type I error: 0.05; power: 0.9
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Threshold for statistical significance: p < 0.05
    Method Regression, Logistic
    Comments Generalized estimating equations (GEE) with independent working correlation to account for correlated data comparing screening and treatment phases
    2. Secondary Outcome
    Title Change in Gastroparesis Cardinal Symptom Index (GCSI) Total and Mean Score and Patient Assessed Gastro-Intestinal Quality of Life (PAGI-QOL) Score
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Participants
    Arm/Group Description Continuous glucose monitoring in conjunction with insulin pump CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump
    Measure Participants 45
    Change in total GCSI score, screening to 12 weeks
    -7.2
    (8.2)
    Change in total GCSI score, screening to 24 weeks
    -7.1
    (9.1)
    Change in GCSI composite, screening to 12 weeks
    -0.6
    (0.9)
    Change in GCSI composite, screening to 24 weeks
    -0.8
    (1.0)
    Change in PAGI-QOL score, screening to 12 weeks
    0.7
    (0.9)
    Change in PAGI-QOL score, screening to 24 weeks
    0.7
    (0.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in total GCSI score from screening to 12 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in total GCSI score from screening to 24 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in GCSI composite score from screening to 12 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in GCSI composite score from screening to 24 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in PAGI-QOL score from screening to 12 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection All Participants
    Comments Null hypothesis: No difference in PAGI-QOL score from screening to 24 weeks of treatment.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Mean change = 0
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method paired t-test
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Adverse events were categorized into 3 categories: (1) severe hypoglycemic events, (2) gastroparesis exacerbations which includes nausea, vomiting, abdominal pain and diarrhea and (3) other which includes cholecystectomy, bilateral otitis media, hyperglycemia, rash, dizziness, and retinal detachment.
    Arm/Group Title All Participants
    Arm/Group Description Continuous glucose monitoring in conjunction with insulin pump CGMS and insulin pump: Use of continuous glucose monitoring system and insulin pump
    All Cause Mortality
    All Participants
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    All Participants
    Affected / at Risk (%) # Events
    Total 16/45 (35.6%)
    Cardiac disorders
    Heart attack, screening/run-in phase 1/45 (2.2%) 1
    Eye disorders
    Retinal detachment, screening/run-in phase 1/45 (2.2%) 1
    Gastrointestinal disorders
    Severe gastroparesis exacerbation, screening/run-in phase 1/45 (2.2%) 2
    Severe gastroparesis exacerbation, treatment phase 1/42 (2.4%) 1
    Abdominal pain, nausea, vomiting, screening/run-in phase 1/45 (2.2%) 1
    Abdominal pain, nausea, vomiting, treatment phase 3/42 (7.1%) 3
    General disorders
    Death of unknown cause, screening/run-in phase 1/45 (2.2%) 1
    Metabolism and nutrition disorders
    Severe hypoglycemic events, screening/run-in phase 2/45 (4.4%) 2
    Severe hypoglycemic events, treatment phase 6/42 (14.3%) 6
    Severe hyperglycemic events, treatment phase 3/42 (7.1%) 3
    Nervous system disorders
    Pain, numbness, paresthesia in hands, screening/run-in phase 1/45 (2.2%) 1
    Other (Not Including Serious) Adverse Events
    All Participants
    Affected / at Risk (%) # Events
    Total 12/45 (26.7%)
    Ear and labyrinth disorders
    Bilateral otitis externa, treatment phase 1/42 (2.4%) 2
    Gastrointestinal disorders
    Non-severe gastroparesis exacerbation, screening/run-in phase 2/45 (4.4%) 2
    Non-severe gastroparesis exacerbation, treatment phase 2/42 (4.8%) 5
    Abdominal pain, nausea, vomiting, screening/run-in phase 2/45 (4.4%) 5
    Abdominal pain, nausea, vomiting, treatment phase 2/42 (4.8%) 2
    Metabolism and nutrition disorders
    Non-severe hyperglycemia, screening/run-in phase 1/45 (2.2%) 1
    Nervous system disorders
    Tingling, disorientation, dizziness, screening/run-in phase 1/45 (2.2%) 1
    Skin and subcutaneous tissue disorders
    Pruritis/itching rash under CGMS site, screening/run-in phase 1/45 (2.2%) 1
    Rash generalized over upper body at CGMS site, treatment phase 1/42 (2.4%) 1
    Surgical and medical procedures
    Cholecystectomy, screening/run-in phase 1/45 (2.2%) 1

    Limitations/Caveats

    Our sample size and treatment durations were somewhat modest to compare severe hypoglycemic episodes and efficacy outcomes before and during treatment.

    More Information

    Certain Agreements

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

    There is NOT 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 Mark Van Natta
    Organization Johns Hopkins Data Coordinating Center
    Phone 410-614-1362
    Email mvannat1@jhu.edu
    Responsible Party:
    Johns Hopkins Bloomberg School of Public Health
    ClinicalTrials.gov Identifier:
    NCT01030341
    Other Study ID Numbers:
    • U01DK074008 GLUMIT-DG
    • U01DK073983
    • U01DK073975
    • U01DK073985
    • U01DK074035
    • U01DK074008
    • U01DK073974
    • U01DK074007
    First Posted:
    Dec 11, 2009
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022