CGM-Assisted Insulin Dosing for Cystic Fibrosis-Related Diabetes

Overseen By Jagdeesh Ullal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Jagdeesh Ullal

Must be taking: Basal bolus insulin

Disqualifiers: Use of CGMs, unable to check sugars

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how two methods of insulin administration can manage blood sugar levels in individuals with cystic fibrosis-related diabetes. It compares a fixed insulin dose before meals with adjusting the dose based on carbohydrate intake. The goal is to determine which method better controls blood sugar spikes, affecting nutrition and overall health. Individuals with cystic fibrosis-related diabetes who already use insulin and have had a lung transplant might be suitable for this trial. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should already be using basal bolus insulin, so you may need to continue with that.

What is the safety track record for the treatments in this trial?

Research has shown that insulin therapy is a recommended and well-known treatment for diabetes related to cystic fibrosis (CFRD). Studies have found that insulin can lower the risk of lung infections and improve overall health in people with CFRD. Importantly, using insulin does not increase the risk of low blood sugar (hypoglycemia) when monitored with a continuous glucose monitor (CGM). This indicates that insulin is generally safe and well-tolerated for managing CFRD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the CGM-assisted insulin dosing approach for cystic fibrosis-related diabetes because it integrates continuous glucose monitoring (CGM) to fine-tune insulin dosing. Unlike the traditional method of fixed insulin doses, this approach allows for adjustments based on real-time glucose levels, potentially improving blood sugar control. By personalizing insulin management with data from CGM, patients may experience fewer glucose fluctuations and better overall health outcomes.

What evidence suggests that CGM-assisted insulin dosing is effective for cystic fibrosis-related diabetes?

In this trial, participants will receive insulin, which previous studies have shown to be the best treatment for diabetes related to cystic fibrosis (CFRD). Research indicates that insulin helps patients with CFRD maintain their weight and control blood sugar levels. While pills have been tested, they do not match insulin's effectiveness for this condition. Insulin is crucial for managing CFRD because it helps the body properly use sugar from food, essential for good nutrition and health in these patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Jagdeesh Ullal, MD

Principal Investigator

University of Pittsburgh Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with cystic fibrosis-related diabetes, including those who've had a lung transplant and are on basal bolus insulin therapy. It's not open to current CGM users or those unable to perform fingerstick blood sugar tests.

Inclusion Criteria

I am older than 18 years.

I am on a basal-bolus insulin regimen.

I have been diagnosed with diabetes due to cystic fibrosis.

Exclusion Criteria

You can't measure your blood sugar using a fingerstick test.

You are using a continuous glucose monitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive meal-time rapid-acting insulin by carbohydrate counting versus fixed-dose rapid-acting insulin

4 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Continuous glucose monitor (CGM)
• Insulin

Trial Overview The study compares two ways of dosing meal-time rapid-acting insulin in cystic fibrosis patients: calculating doses based on carbohydrate intake versus using fixed doses. The effectiveness will be measured using continuous glucose monitors.

How Is the Trial Designed?

Group I: Fixed Dosing, Followed by Carbohydrate Counting Experimental Treatment 2 Interventions

Dosing of premeal insulin with fixed doses

Insulin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Insulin for:

• Diabetes mellitus

Approved in United States as Insulin for:

• Diabetes mellitus

Approved in Canada as Insulin for:

• Diabetes mellitus

Who Is Running the Clinical Trial?

Jagdeesh Ullal

Lead Sponsor

Trials

1

Recruited

10+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

A comprehensive review of 50 studies over the past 20 years revealed significant differences in bioactivity between human insulin and various insulin analogues, affecting metabolism, cell growth, and other cellular functions.

The clinical implications of these differences in bioactivity are still unclear and require further investigation to understand their impact on different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. Werner, H., Chantelau, EA.[2021]

A pilot study on cystic fibrosis-related diabetes (CFRD) showed that using a bionic pancreas, which can deliver both insulin and glucagon, resulted in good glycemic control with average glucose levels below 150 mg/dl and minimal instances of hypoglycemia.

Participants using the bionic pancreas reported higher satisfaction with their treatment and found diabetes management to be less burdensome compared to traditional insulin injections, suggesting a promising alternative for CFRD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study. Sherwood, JS., Jafri, RZ., Balliro, CA., et al.[2021]

In a case study of an adult with long-standing cystic fibrosis-related diabetes (CFRD), treatment with ivacaftor led to sustained improvements in glycemic control, suggesting potential benefits beyond insulin therapy.

This finding aligns with previous small studies indicating that ivacaftor may enhance endogenous insulin secretion in patients with specific cystic fibrosis mutations, highlighting its possible role in managing CFRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained Glycemic Control With Ivacaftor in Cystic Fibrosis-Related Diabetes. Christian, F., Thierman, A., Shirley, E., et al.[2022]

In a case series of seven children with cystic fibrosis-related diabetes (CFRD) treated with the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), four children were able to stop insulin completely, and two required significantly lower doses, indicating improved glycaemic control.

The treatment led to similar glycaemic control even with reduced or no insulin, but close monitoring for hypoglycaemia is essential, as some children experienced low blood sugar levels despite not needing insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvements in glucose regulation in children and young people with cystic fibrosis related diabetes following initiation of Elexacaftor/Tezacaftor/Ivacaftor. Park, J., Walsh, A., Kerr, S., et al.[2023]

In a pilot study involving 19 adults using the MiniMed™ 670G system, both Novolog® and Fiasp® insulin showed similar effectiveness in managing blood sugar levels, with no significant differences in time spent within the target glucose range or hypoglycemia rates.

Fiasp® required a slightly higher daily insulin dose compared to Novolog®, but both insulins resulted in comparable glycemic outcomes, indicating that either can be effectively used in a hybrid closed-loop system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast-Acting Insulin Aspart Use with the MiniMedTM 670G System. Hsu, L., Buckingham, B., Basina, M., et al.[2022]

In a study involving 1008 patients, short-acting insulin lispro and regular insulin Humulin R showed similar effectiveness in controlling blood sugar levels and had comparable safety profiles, with no significant differences in hypoglycemia incidents.

After a year of continued lispro therapy, glycosylated hemoglobin (HbA1C) levels returned to baseline, indicating that while lispro was well tolerated in the short term, long-term efficacy may need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lispro insulin as premeal therapy in type 1 diabetes: comparison with Humulin R. Daniels, AR., Bruce, R., McGregor, L.[2022]

Dasiglucagon is a safe and effective treatment for severe hypoglycemia in type 1 diabetes, showing a similar safety profile to reconstituted glucagon with no serious adverse events reported in trials involving adults.

In terms of efficacy, dasiglucagon provided a rapid recovery from insulin-induced hypoglycemia, with a median recovery time of 10 minutes, significantly faster than the 40 minutes observed with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetes. Heller, S., Battelino, T., Bailey, TS., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10915598/

The Changing Landscape of Treatment for Cystic Fibrosis ... Patients with Cystic Fibrosis related diabetes [CFRD] are treated with insulin and high calorie diets to maintain body mass.

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15844

Cystic fibrosis‐related diabetes develops from a combination ... Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period. 1 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1569199319308355

Cystic fibrosis related diabetes: Medical management Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance. J Endocrinol Investig, 29 (3) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1513574/

Insulin versus oral agents in the management of Cystic ... Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin.

5. diabetesjournals.org diabetesjournals.org/care/article/33/12/2697/39264/Clinical-Care-Guidelines-for-Cystic-Fibrosis

Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes The available data suggest that oral agents are not as effective as insulin in CFRD. Four studies (with a total of 153 participants) compared ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12574440/

Assessing the efficacy, safety and utility of hybrid closed-loop ... The recommended management of CFRD is insulin therapy, which is associated with reduced risk of pulmonary infections and improvements in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2214623724000036

The Changing Landscape of Treatment for Cystic Fibrosis ... There were no changes in A1c or random blood glucose levels in CFRD patients after one year of treatment with ETI, which is consistent with our findings. It is ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8094754/

Drug treatments for managing cystic fibrosis‐related diabetes The Cystic Fibrosis Foundation recommends both short‐term and long‐acting insulin therapy when cystic fibrosis‐related diabetes (CFRD) has been diagnosed.

9. diabetesjournals.org diabetesjournals.org/care/article/47/1/101/153790/Randomized-Trial-of-the-Insulin-Only-iLet-Bionic

Randomized Trial of the Insulin-Only iLet Bionic Pancreas for ... Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting ...

10. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1228153/full

Effects of insulin therapy optimization with sensor ... Continuous glucose monitoring guided insulin therapy is associated with improved clinical outcomes in cystic fibrosis-related diabetes. J ...