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

13 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Continuous Glucose Monitoring System for Cystic Fibrosis-Related Diabetes?

Research shows that using continuous glucose monitoring systems, like the Tandem t:slim X2 pump with Control IQ technology, can improve blood sugar control in people with cystic fibrosis-related diabetes by increasing the time their blood sugar stays within the target range and reducing high blood sugar levels. ^{1 2 3 4 5}

Is CGM-assisted insulin dosing safe for humans?

Research shows that various types of insulin, including those used with continuous glucose monitoring systems, have been studied for safety in humans. Studies have generally found them to be safe, with no significant differences in safety outcomes between different insulin types when used in systems like the MiniMed 670G. ^{6 7 8 9 10}

How does the drug insulin differ from other treatments for cystic fibrosis-related diabetes?

Insulin is the recommended treatment for cystic fibrosis-related diabetes because it directly helps manage blood sugar levels, even though it may not always provide optimal control. Unlike oral medications, insulin is injected, which can be more invasive, but it offers flexibility in managing the variable food intake and activity levels common in cystic fibrosis patients. ^{1 11 12 13 14}

What is the purpose of this trial?

The aim of this study is to assess the utility of CGMs to determine the optimal method to dose meal-time insulin. The investigators will examine glucose excursions in patients with CF who will dose meal-time rapid-acting insulin by carbohydrate counting versus fixed-dose rapid-acting insulin. The carbohydrate ratio and fixed doses will be determined by existing doses, total daily insulin doses, body weight, and insulin sensitivity along with predisposition to hypoglycemia. Bolus insulin dosing is an important part of CFRD management due to the high nutritional demands of these patients. If dosed incorrectly, this could lead to marked hyperglycemia and could worsen nutritional status due to urinary glucose losses. In this project, the investigators will perform a within-subjects' comparison of the 2 standard methods of meal-time rapid-acting insulin dosing.

Research Team

Jagdeesh Ullal, MD

Principal Investigator

University of Pittsburgh Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Insulin and glucose excursion following premeal insulin lispro or repaglinide in cystic fibrosis-related diabetes. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study. [2021]

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

Sustained Glycemic Control With Ivacaftor in Cystic Fibrosis-Related Diabetes. [2022]

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

The Effect of Control IQ Hybrid Closed Loop Technology on Glycemic Control in Adolescents and Adults with Cystic Fibrosis-Related Diabetes. [2023]

5. Switzerland 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. [2023]

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

Fast-Acting Insulin Aspart Use with the MiniMedTM 670G System. [2022]

7. England 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. [2021]

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

Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetes. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Lispro insulin as premeal therapy in type 1 diabetes: comparison with Humulin R. [2022]

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

Patient and physician satisfaction with the Humulin/Humalog Pen, a new 3.0-mL prefilled pen device for insulin delivery. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study. [2018]

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

Use of sensor-augmented insulin pump in patient with diabetes and cystic fibrosis: evidence for improvement in metabolic control. [2011]

13. Ireland pubmed.ncbi.nlm.nih.gov

Diabetes mellitus in childhood cystic fibrosis. [2009]

14. England pubmed.ncbi.nlm.nih.gov

Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus. [2021]