Continuous Glucose Monitoring for Type 1 Diabetes

Overseen By Beth Pappenfus

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Minnesota

Must be taking: Insulin

Disqualifiers: Pregnancy, Major medical conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This RCT aims to improve T1D care in East African children and young adults by testing the hypothesis that enabling patients to continuously monitor glucose levels with flash CGM technology will improve glucose time-in-range (glucose level 70-180 mg/dl). A second primary endpoint is to perform a cost analysis on flash glucose monitoring compared to 3x/day SMBG, to determine whether this technology is cost-effective in the setting of a less-resourced nation. After a 2 week assessment with blinded CGM when a potential subject's ability to wear CGM is confirmed, subjects will be enrolled for 12 months in randomized, open label study, with a primary endpoint measurement at 6 months. All subjects will receive monthly diabetes self-management education. For the first six months, months 1-6: * Half of patients (n=90) will be randomized to an unblinded FreeStyle Libre 2 CGM.They and their care providers will be able to continuously see their CGM glucose levels to assist in insulin adjustment. * Half of patients (n=90) will be given sufficient test strips for 3x daily SMBG while wearing blinded CGM (control group). Neither they nor their care providers will be able to see their CGM glucose levels (the blinded CGM is simply for outcome measurement, not an intervention). As per usual clinical practice, only the SMBG glucose levels will be available to assist in insulin adjustment. * The change between baseline to 6 months in CGM-derived glucose percent time-in- range will be compared between groups (first primary study endpoint). For the second six months, months 7-12: * The control group will switch to unblinded CGM months 7-12 (their data months 7-12 months will be compared to their data months 1-6 as part of the primary endpoint assessment). * The patients who wore the unblinded CGM months 1-6 will continue for another 6 months to assess the impact of wearing the CGM for 12 continuous months (a secondary endpoint). Once the clinical portion of the study is complete, study investigators who are health economists from the Uganda Ministry of Health will perform a costs analysis (second primary endpoint).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on using continuous glucose monitoring and does not mention changes to existing medication regimens.

What data supports the effectiveness of the treatment FreeStyle Libre 2 for Type 1 Diabetes?

Research shows that patients with Type 1 Diabetes using the FreeStyle Libre 2 system report high satisfaction and improved metabolic outcomes, which means better control of their blood sugar levels. Additionally, switching from the original FreeStyle Libre to the FreeStyle Libre 2 has been associated with better glucose monitoring results. ^{1 2 3 4 5}

Is the FreeStyle Libre system safe for use in humans?

The FreeStyle Libre system is generally safe for use, but some people may experience skin reactions like allergic contact dermatitis (skin inflammation) due to an ingredient in the adhesive called isobornyl acrylate. ^{2 6 7 8 9}

How is the Libre 2 treatment different from other treatments for type 1 diabetes?

Libre 2 is unique because it allows for continuous glucose monitoring without the need for regular finger pricks, and it can send automatic alerts to a device when blood sugar levels are abnormal, making it more convenient and proactive compared to traditional glucose meters. ^{2 10 11 12 13}

Research Team

Antoinette Moran, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for children and young adults aged 4-26 in Uganda with Type 1 Diabetes (T1D) who have been managing their condition with insulin for at least a year. Participants need to have access to a cell phone, be able to visit the clinic monthly, and not be pregnant or planning pregnancy within a year. They must also not already own a CGM device.

Inclusion Criteria

Access to a cell phone (nearly ubiquitous in Uganda, even in remote areas)

I am under 18 and have a parent or guardian to consent for me, or I am 18-26 and can consent for myself.

I have been diagnosed with Type 1 Diabetes for at least a year.

Exclusion Criteria

Participant deemed unlikely or unable to comply with the protocol

Unwilling or unable to be seen monthly at the pediatric diabetes clinic

The patient already has a continuous glucose monitor (CGM).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment Phase 1

Participants are randomized to either unblinded CGM or 3x daily SMBG with blinded CGM for 6 months

6 months

Monthly diabetes self-management education visits

Treatment Phase 2

Control group switches to unblinded CGM, and the initial CGM group continues for another 6 months

6 months

Monthly diabetes self-management education visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Libre 2
• Libre Pro

Trial Overview The study tests if using flash Continuous Glucose Monitoring (CGM) technology helps maintain blood sugar levels within the target range better than standard monitoring. Half of the participants will use FreeStyle Libre 2 CGM for real-time glucose tracking, while the other half will start with standard blood sugar testing before switching to CGM after six months.

Participant Groups

Group I: Libre 2 Experimental Treatment 1 Intervention

Half of patients will be randomized to wear an unblinded FreeStyle Libre 2 CGM for 12 months. Sensor glucose data will be continuously available to patients and their providers. Primary outcome measurement occurs at 6 months.

Group II: SMBG levels 3x/daily (standard diabetes management) Placebo Group 1 Intervention

Half of subjects will be given sufficient test strips to test 3x per day for the first 6 months of the study, as is usual clinical practice. They wear a blinded FreeStyle Libre Pro CGM monthly during this time-the blinded device is simply to collect study data, the data will not be available to the patient or their provider for clinical use. They will use the 3x daily SMBG data for insulin adjustment, as per usual standard of care. For the final 6 months (7-12), this group will switch to unblinded CGM patients and providers will have full access to CGM data.

Libre 2 is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as FreeStyle Libre 2 for:

• Type 1 diabetes
• Type 2 diabetes

Approved in United States as FreeStyle Libre 2 for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Canada as FreeStyle Libre 2 for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Japan as FreeStyle Libre 2 for:

• Type 1 diabetes
• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a study of 86 patients with type 1 diabetes using the Freestyle Libre 2 (FSL2) system for 12 weeks, significant improvements were observed in glucose metrics, including a reduction in low glucose events and an increase in time spent within the target glucose range.

Patients reported high satisfaction with the FSL2 system, indicating it provided benefits with minimal discomfort, suggesting that it is a favorable option for continuous glucose monitoring in managing type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Patient-reported Satisfaction and Metabolic Outcomes Following Initiation of the Second Generation of Flash Glucose Monitoring in Patients with Type 1 Diabetes Al Hayek, A., Robert, AA., Alzahrani, WM., et al.[2023]

The FreeStyle Libre Flash continuous glucose monitoring (FSL-CGM) system showed that 85.5% of its readings from the arm fell within the clinically acceptable range when compared to a standard blood glucose measurement, indicating good efficacy for monitoring glucose levels in patients with diabetes.

However, the FSL-CGM system tended to underestimate glucose levels at lower ranges and overestimate them at higher ranges, particularly after meals, suggesting that users should be cautious and follow optimized instructions for accurate daily management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of the FreeStyle Libre Flash glucose monitoring system in patients with type 1 and 2 diabetes mellitus. Fokkert, MJ., van Dijk, PR., Edens, MA., et al.[2022]

The first-generation FreeStyle Libre isCGM device showed a mean average relative difference (MARD) of 15.6% in sensor glucose levels compared to capillary blood glucose, indicating a moderate level of accuracy in monitoring glucose levels among 91 participants.

Participants with contact dermatitis experienced a significantly higher MARD of 27.4%, suggesting that skin complications may negatively impact the accuracy of glucose readings from the isCGM device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study. Toyoda, M., Murata, T., Hirota, Y., et al.[2023]

In a study involving 148 insulin-treated type 2 diabetes patients, the use of the FreeStyle Libre Pro™ glucose monitoring system significantly reduced HbA1c levels by 4.9 mmol/mol (0.44%) without increasing the risk of hypoglycemia.

Patients using the Libre Pro system reported higher treatment satisfaction compared to those who only self-monitored blood glucose, indicating that this monitoring system can enhance the overall management experience for diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in HbA1c using professional flash glucose monitoring in insulin-treated type 2 diabetes patients managed in primary and secondary care settings: A pilot, multicentre, randomised controlled trial. Ajjan, RA., Jackson, N., Thomson, SA.[2022]

In a study of 672 adults with type 1 diabetes, switching to Freestyle Libre 2 led to a significant reduction in time below range (TBR) by a median of 1.0% after 12 months, indicating better management of low glucose levels.

Users of high glucose alerts experienced significant improvements in time in range (TIR) and overall glucose metrics, suggesting that utilizing alert functions can enhance glucose control in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in continuous glucose monitoring metrics and predictors of improvement 12 months after conversion from Freestyle Libre to Freestyle Libre 2. Stimson, RH., Dover, AR., Strachan, MWJ., et al.[2023]

An 8-year-old girl with type 1 diabetes developed severe allergic contact dermatitis from the adhesive of the FreeStyle® Libre continuous glucose monitoring device, highlighting a potential safety concern.

Patch testing confirmed that she was allergic to isobornyl acrylate, a component in the adhesive, indicating that while the FreeStyle® Libre is a useful tool for glucose monitoring, it can cause adverse skin reactions in some users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic contact dermatitis caused by isobornyl acrylate when using the FreeStyle&#174; Libre. Mine, Y., Urakami, T., Matsuura, D.[2023]

The FreeStyle Navigator Continuous Glucose Monitoring System was found to be safe and effective for adults with type 1 or 2 diabetes, significantly reducing time spent in hypoglycemia by 55% during the unmasked period of the study.

Participants reported high satisfaction with the system, and the accuracy of glucose readings was validated, with 77.2% of results falling in the clinically acceptable Clarke error grid zone A, indicating reliable monitoring for better glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a continuous glucose monitoring system for home-use conditions. Bode, B., Silver, M., Weiss, R., et al.[2019]

Five patients with allergic contact dermatitis (ACD) from the Freestyle Libre glucose monitoring system were identified as sensitized to isobornyl acrylate (IBOA), the allergen responsible for their reactions.

Gas chromatography-mass spectrometry (GC/MS) confirmed that the Freestyle Libre sensor contains IBOA, while the Dexcom sensor is free of this allergen, making it a safe alternative for these patients without causing skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dexcom glucose monitoring system-An isobornyl acrylate-free alternative for diabetic patients. Oppel, E., Kamann, S., Reichl, FX., et al.[2019]

The Sugar Sleuth mobile app, used alongside the FreeStyle Libre™ glucose sensor, led to a significant average reduction in A1c levels by 0.5% over 14 weeks in adults with type 1 diabetes, indicating improved glycemic control.

Participants also reported a decrease in daily carbohydrate intake by an average of 43 grams, suggesting that the app effectively supported dietary management, although no significant changes were observed in other glycemic metrics or insulin dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating a Glucose-Sensor-Based Tool to Help Clinicians and Adults With Type 1 Diabetes Improve Self-Management Skills. Toschi, E., Fisher, L., Wolpert, H., et al.[2019]

The FreeStyle Libre Flash continuous glucose monitoring system (FSL-CGM) demonstrated high accuracy at alternative sites, with the chest and back sensors showing 98% and 97.9% accuracy compared to the arm sensor in a study involving 20 participants with type 1 diabetes.

Participants preferred the arm and chest sensor sites for their accuracy and usability, although all sensors showed greater variability during rapid glucose changes, highlighting the need for careful interpretation of readings during such conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Where can you wear your Libre? Using the FreeStyle Libre continuous glucose monitor on alternative sites. Hall, RM., Dyhrberg, S., McTavish, A., et al.[2022]

The Abbott FreeStyle Libre continuous glucose monitoring systems (CGM 1, CGM 2, and CGM 3) maintained their functionality and data integrity after exposure to X-ray, CT, and MRI simulations, indicating they are safe to wear during these diagnostic procedures.

The sensors experienced minimal displacement forces during MRI, well below the threshold needed to dislodge them, confirming that patients can safely continue using these sensors during imaging without risk of losing them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Functional Integrity of Continuous Glucose Monitoring Sensors When Used During Radiologic Procedures Under High Exposure Conditions. Matievich, W., Kiaie, N., Dunn, TC.[2023]

A study involving 15 patients revealed that the FreeStyle® Libre glucose sensor can cause allergic contact dermatitis, primarily due to its adhesive component.

Isobornyl acrylate was identified as a significant allergen in these cases, with 12 out of 13 tested patients showing sensitization to it, highlighting the need for awareness of potential allergic reactions to this medical device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor. Herman, A., Aerts, O., Baeck, M., et al.[2022]

The use of additional readers with the FreeStyle Libre flash glucose monitoring system significantly reduced self-reported glycated hemoglobin levels and episodes of hypoglycemia among 132 patients with diabetes, indicating improved metabolic control.

Patients reported enhanced quality of life due to fewer limitations in daily activities and social interactions, suggesting that the combination of flash glucose monitoring and additional readers effectively supports diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Using Additional Readers for Flash Glucose Monitoring System on Metabolic Control, Safety, and the Incidence of Complications in Patients With Diabetes Mellitus. Kublin, O., Stępień, M.[2021]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Assessment of Patient-reported Satisfaction and Metabolic Outcomes Following Initiation of the Second Generation of Flash Glucose Monitoring in Patients with Type 1 Diabetes [2023]

2. England pubmed.ncbi.nlm.nih.gov

Performance of the FreeStyle Libre Flash glucose monitoring system in patients with type 1 and 2 diabetes mellitus. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Reduction in HbA1c using professional flash glucose monitoring in insulin-treated type 2 diabetes patients managed in primary and secondary care settings: A pilot, multicentre, randomised controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Changes in continuous glucose monitoring metrics and predictors of improvement 12 months after conversion from Freestyle Libre to Freestyle Libre 2. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

Allergic contact dermatitis caused by isobornyl acrylate when using the FreeStyle&#174; Libre. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of a continuous glucose monitoring system for home-use conditions. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The Dexcom glucose monitoring system-An isobornyl acrylate-free alternative for diabetic patients. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluating a Glucose-Sensor-Based Tool to Help Clinicians and Adults With Type 1 Diabetes Improve Self-Management Skills. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Where can you wear your Libre? Using the FreeStyle Libre continuous glucose monitor on alternative sites. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Safety and Functional Integrity of Continuous Glucose Monitoring Sensors When Used During Radiologic Procedures Under High Exposure Conditions. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Effect of Using Additional Readers for Flash Glucose Monitoring System on Metabolic Control, Safety, and the Incidence of Complications in Patients With Diabetes Mellitus. [2021]