End-Stage Renal Disease, Type 2 Diabetes
Conditions
Keywords
ESRD, Continuous Glucose Monitoring, Diabetes
Brief summary
The study is conducted to assess the efficacy of real-time CGM data in preventing hypoglycemia in patients with type 2 diabetes and end-stage kidney disease (ESKD), treated with insulin therapy and receiving hemodialysis.
Detailed description
The study is conducted to assess the efficacy of real-time CGM data in preventing hypoglycemia among patients with type 2 diabetes (DM2), treated with insulin and receiving hemodialysis. The study will provide novel insights into the glycemic exposure patterns among dialysis patients and will provide preliminary data for future outcomes-based studies determining the best glycemic targets for this group.
Interventions
DEVICEDexcom Real-time G6 Continuous Glucose Monitoring System (CGM)
Dexcom G6, a factory-calibrated CGM system, is innovative in many aspects: 1) it does not require finger stick POC BG for calibration, 2) the sensor is small, compact, light-weight, 3) has no interference with several substance and drugs, and 4) protective urgent low soon alarm, with proven prediction of hypoglycemia within 20 minutes in advance. Dexcom G6 monitors glucose continuously (24 hrs) and displays real-time glucose values, glucose trends/arrows and alarms, including the urgent low soon alarm (predictive of hypoglycemia \< 55 mg/dL within the preceding 20 minutes). Diagnostic Test: Real-time CGM will be used to collect outcomes variables
DEVICEPOC Glucose Testing
POC BG (standard of care) uses commercially-available glucose meters for blood glucose monitoring. It is approved to be used in dialysis populations. Diagnostic Test: Professional CGM will be used to collect outcomes variables (including during the POC BG testing).
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Patients with type 2 DM treated with insulin and receiving hemodialysis will use a real-time/personal CGM for 4 weeks (Intervention-Control Group), then 2 weeks of wash-out period, and cross over to use POC BG for 4 weeks; and vice versa (Control-Intervention Group).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* adult subjects with type 2 diabetes * receiving hemodialysis (for at least 90 days) * treated with insulin therapy \[basal insulin alone (glargine U100, glargine U300, detemir, degludec, NPH)\], or in combination with bolus insulin (at least one or more injections of aspart, lispro, glulisine, regular insulin) or in combination with incretin therapy (DPPIV or GLP1) * willingness to wear the CGM * currently performing self-monitored blood glucose (at least 2 times daily).
Exclusion criteria
* use of sulfonylureas or thiazolidinediones alone or in combination with insulin * use of personal/real-time CGM 3 months prior to study entry (blinded CGM is allowed) * prior use of insulin pumps or hybrid close loop systems (for at least the prior 28 days) * current or anticipated use of stress steroids doses (prednisone ≤5mg or its equivalent is allowed) * subjects who are sensitive or allergic to adhesive * extensive skin changes/diseases that preclude wearing the required number of devices on normal skin (e.g., extensive psoriasis, recent burns or severe sunburn, extensive eczema, extensive scarring, extensive tattoos, dermatitis herpetiformis) at the proposed wear sites * any condition that, in the opinion of the Investigator, would interfere with their participation in the trial (e.g., marked visual or hearing impairment, active alcohol or drug abuse, mental illness) or pose excessive risk to study staff handling venous blood samples * situations that will limit the subject's ability to comply with the protocol (per investigator discretion) * active malignancy * unable to give informed consent * at least 10% of time spent in clinical relevant hypoglycemia (\<54 mg/dl) during blinded CGM period * significant hypoglycemia (\< 40 mg/dL) * severe hyperglycemia (BG\> 400 mg/dL) * extensive skin abnormalities at insertion sites * pregnancy or breastfeeding * severe anemia (Hemoglobin \< 5 mg/dl) * polycythemia (Hemoglobin \>17 mg/dl) * subjects taking acetaminophen (more than 1 gr every six hours) * hydroxyurea (may cause interference with the sensor membrane).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in Mean Percentage Time-in-hypoglycemia (< 70 mg/dL) | 8 weeks (after completion of both phases) | Differences in mean percentage time-in-hypoglycemia (\< 70 mg/dL) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. Participants will use either CGM or POC BG testing (during each assignment phase) for insulin adjustment. CGM will be used to collect outcomes variables during each phase (including during the POC BG testing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Time in Target Range (70-180 mg/dl) | 8 weeks (after completion of both phases) | % time in target range (70-180 mg/dl) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. Participants will use either CGM or POC BG testing (during each assignment phase) for insulin adjustment. CGM will be used to collect outcomes variables during each phase (including during the POC BG testing). |
| Mean % Time in Hypoglycemia (< 54 mg/dL) | 8 weeks (after completion of both phases) | % time in hypoglycemia (\<54 mg/dL) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. |
| % Time in Hyperglycemia (>180 mg/dL) | 8 weeks (after completion of both phases) | % time in hyperglycemia (\>180 mg/dL) during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. |
| % Time in Hyperglycemia (>250 mg/dl) | 8 weeks (after completion of both phases) | % time in hyperglycemia (\>250 mg/dL) during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. |
| HbA1C at 3 Months Follow up | Baseline, 3 months post-intervention | HbA1C at 3 months follow up from baseline. Data will be exported from the electronic medical records. |
| Mean Amplitude of Glucose Excursions (MAGE) | 8 weeks (after completion of both phases) | Mean amplitude of glucose excursions (MAGE) will be measured during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. |
| Number of Hospitalization or Emergency Room Visits for Hypoglycemia | Baseline, 3 months post-intervention | Rate of hospitalization or emergency room (ER) visits for hypoglycemia will be recorded at baseline (including 1 year prior to the start of the study) and at 3 months post study intervention. |
| Number of Hospitalization or Emergency Room Visits for Diabetes Ketoacidosis (DKA) | Baseline, 3 months post-intervention | Rate of hospitalization or emergency room visits for diabetes ketoacidosis will be recorded at baseline (including 1 year prior to the start of the study) and at 3 months post study intervention. |
| Glycemic Variability [% Coefficient of Variation (%CV) | 8 weeks (after completion of both phases) | % coefficient of variation will be measured during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. |
Countries
United States
Participant flow
Pre-assignment details
Of the 66 individuals who signed the informed consent form (ICF), 53 took part in the study. The remaining 13 individuals did not proceed to the study due to screening failure. Therefore, the following tables include data only from the 53 participants who began the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received either Real-time Dexcom CGM Intervention or POC-BG Intervention first, and then switch to the remaining intervention after a 2 week wash out period.
Participants will use either CGM or POC BG testing (during each assignment phase) for insulin adjustment. CGM will be used to collect outcomes variables during each phase (including during the POC BG testing). | 53 |
| Total | 53 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 57.36 years STANDARD_DEVIATION 10.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Region of Enrollment United States | 53 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 39 |
| other Total, other adverse events | 4 / 39 | 4 / 39 |
| serious Total, serious adverse events | 0 / 39 | 0 / 39 |
Outcome results
Primary
Differences in Mean Percentage Time-in-hypoglycemia (< 70 mg/dL)
Differences in mean percentage time-in-hypoglycemia (\< 70 mg/dL) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. Participants will use either CGM or POC BG testing (during each assignment phase) for insulin adjustment. CGM will be used to collect outcomes variables during each phase (including during the POC BG testing).
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | Differences in Mean Percentage Time-in-hypoglycemia (< 70 mg/dL) | 1.24 percentage of time in hypoglycemia | Standard Deviation 1.82 |
| Professional Dexcom CGM (Blinded) | Differences in Mean Percentage Time-in-hypoglycemia (< 70 mg/dL) | 1.19 percentage of time in hypoglycemia | Standard Deviation 2.79 |
Secondary
Glycemic Variability [% Coefficient of Variation (%CV)
% coefficient of variation will be measured during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM.
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | Glycemic Variability [% Coefficient of Variation (%CV) | 0.30 percentage of coefficient of variation | Standard Deviation 0.05 |
| Professional Dexcom CGM (Blinded) | Glycemic Variability [% Coefficient of Variation (%CV) | 0.31 percentage of coefficient of variation | Standard Deviation 0.05 |
Secondary
HbA1C at 3 Months Follow up
HbA1C at 3 months follow up from baseline. Data will be exported from the electronic medical records.
Time frame: Baseline, 3 months post-intervention
Population: Per standard of care, HbA1c was not repeated during the RCT before the three-month follow-up of the study (it was not collected by the dialysis center).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real-time Dexcom CGM | HbA1C at 3 Months Follow up | Baseline | 7.21 percent of RBCs with glycated hemoglobin | Standard Deviation 1.66 |
Secondary
Mean Amplitude of Glucose Excursions (MAGE)
Mean amplitude of glucose excursions (MAGE) will be measured during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM.
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | Mean Amplitude of Glucose Excursions (MAGE) | 71.45 mg/dL | Standard Deviation 19.71 |
| Professional Dexcom CGM (Blinded) | Mean Amplitude of Glucose Excursions (MAGE) | 72.24 mg/dL | Standard Deviation 18.63 |
Secondary
Mean % Time in Hypoglycemia (< 54 mg/dL)
% time in hypoglycemia (\<54 mg/dL) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM.
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | Mean % Time in Hypoglycemia (< 54 mg/dL) | 0.46 percentage of time in hypoglycemia | Standard Deviation 1.26 |
| Professional Dexcom CGM (Blinded) | Mean % Time in Hypoglycemia (< 54 mg/dL) | 0.55 percentage of time in hypoglycemia | Standard Deviation 2.1 |
Secondary
Number of Hospitalization or Emergency Room Visits for Diabetes Ketoacidosis (DKA)
Rate of hospitalization or emergency room visits for diabetes ketoacidosis will be recorded at baseline (including 1 year prior to the start of the study) and at 3 months post study intervention.
Time frame: Baseline, 3 months post-intervention
Population: Participants did not stay in the study for 3 months. Hence, data at 3 months was not possible to be collected by the dialysis center.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Real-time Dexcom CGM | Number of Hospitalization or Emergency Room Visits for Diabetes Ketoacidosis (DKA) | Number of hospitalization or emergency room visits for DKA at Baseline | 4 events |
Secondary
Number of Hospitalization or Emergency Room Visits for Hypoglycemia
Rate of hospitalization or emergency room (ER) visits for hypoglycemia will be recorded at baseline (including 1 year prior to the start of the study) and at 3 months post study intervention.
Time frame: Baseline, 3 months post-intervention
Population: Participants did not stay in the study for 3 months. Hence, data at 3 months was not possible to be collected by the dialysis center.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Real-time Dexcom CGM | Number of Hospitalization or Emergency Room Visits for Hypoglycemia | Number of hospitalization and emergency room visits for hypoglycemia at baseline | 21 number of events |
Secondary
% Time in Hyperglycemia (>180 mg/dL)
% time in hyperglycemia (\>180 mg/dL) during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM.
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | % Time in Hyperglycemia (>180 mg/dL) | 35.07 percentage of time in hyperglycemia | Standard Deviation 23.94 |
| Professional Dexcom CGM (Blinded) | % Time in Hyperglycemia (>180 mg/dL) | 44.57 percentage of time in hyperglycemia | Standard Deviation 22.9 |
Secondary
% Time in Hyperglycemia (>250 mg/dl)
% time in hyperglycemia (\>250 mg/dL) during the intervention phase in both groups.(i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM.
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | % Time in Hyperglycemia (>250 mg/dl) | 13.18 percentage of time in hyperglycemia | Standard Deviation 14.72 |
| Professional Dexcom CGM (Blinded) | % Time in Hyperglycemia (>250 mg/dl) | 18.91 percentage of time in hyperglycemia | Standard Deviation 18.76 |
Secondary
% Time in Target Range (70-180 mg/dl)
% time in target range (70-180 mg/dl) during the intervention phase in both groups (i.e. Real-time Dexcom CGM During CGM Intervention vs. Professional Dexcom CGM During Point-of-Care Glucose Intervention), as measured by CGM. Participants will use either CGM or POC BG testing (during each assignment phase) for insulin adjustment. CGM will be used to collect outcomes variables during each phase (including during the POC BG testing).
Time frame: 8 weeks (after completion of both phases)
Population: Population analyzed per group included patients with usable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real-time Dexcom CGM | % Time in Target Range (70-180 mg/dl) | 63.69 percentage of time in target range | Standard Deviation 23.58 |
| Professional Dexcom CGM (Blinded) | % Time in Target Range (70-180 mg/dl) | 54.24 percentage of time in target range | Standard Deviation 22.25 |