Glucose Metabolism in Cystic Fibrosis Related Diabetes (CFRD)

Glucose Metabolism in CFRD: Exploring the Role of CFTR Modulators in Metabolic Dysfunction

The study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI). CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI) will be the control group.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis Related Diabetes

Detailed Description

This is a mechanistic observational study. A physiological challenge of a single mixed meal tolerance test (MMTT) is administered, which will enable a comprehensive assessment of multiple parameters of glucose turnover, insulin secretion, insulin sensitivity and lipolysis in individuals with CFRD. The MMTT is the gold standard for measuring both insulin action and secretion simultaneously with glucose kinetics. The pilot study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI).

We plan to gather critical preliminary data on the following aspects of CFRD:

1. Abnormalities in specific components (basal vs. static vs. dynamic) of beta-cell function in CFRDF508del+ETI and in CFRD-ETI individuals.
2. Effects of ETI on components of beta cell function.
3. Effects of CFTR mutation and of CFTR modulators (CFRDF508del+ETI) on insulin sensitivity and post prandial glucose turnover in CFRD.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Rita Basu, MD; Phone Number: 205-934-1200; Email: rbasu@uabmc.edu
• Study Contact Backup: Name: Ananda Basu, MD; Phone Number: 205-934-1202; Email: anandabasu@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 352294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Tavares R Donerlson, BA; Phone Number: 2054848306; Email: Tdonerlson@uabmc.edu
      • Contact: John M Mullin, BS; Phone Number: 2672290194; Email: jmmullin@uabmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with Cystic Fibrosis related Diabetes (CFRD)

Description

Inclusion Criteria:

• Individuals who have at least one copy of the F508 deletion and are on ETI medications and individuals who have a different mutation and are not eligible for ETI medications
• Age 21-75 years at time of consent
• BMI 19-50 kg/m2 (In Asians BMI is ~ 2 points lower for comparison so it is 17-48 kg/m2)
• Creatinine ≤ 1.4 mg/dl in women and ≤ 1.5 mg/dl in men
• HbA1c ≤ 11% lifestyle treatment or mono/combination therapy with oral hypoglycemic agents (e.g. metformin or sulphonylurea or SGLT2i) and/or insulin.
• Willing to be at a stable weight for duration of the study.
• An understanding of and willingness to follow the protocol and sign the informed consent

Exclusion Criteria:

• Debilitating chronic disease
• Anemia <10 gm/dL in females and <11.0 gm/dL in males
• Symptoms of undiagnosed illness on history/exam
• Abuse of alcohol or recreational drugs
• Pregnancy
• Active hepatic disease
• Current use of the following drugs and supplements: corticosteroids, benzodiazepines, opiates, barbiturates, anticoagulant therapy
• Any other medication that the investigator believes is a contraindication to the subject's participation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
CFRD F508del +ETI; CFRD with at least one copy of F508del currently on elexacaftor/tezacaftor/ivacaftor (CFRDF508del+ETI),
CFRD-ETI; CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disposition Index in CFRD	Disposition Index (DI - β-cell responsivity appropriate to the degree of insulin resistance) is higher in CFRDF508del+ETI when compared to CFRD with a mutation not eligible to be on ETI (CFRD-ETI).	Day 1 During the Mixed meal test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post prandial glucose turnover	Post prandial glucose turnover is improved in CFRDF508del+ETI when compared to CFRD with a mutation not eligible to be on ETI (CFRD-ETI).	Day 1 During the mixed meal test

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Rita Basu, MD, UAB Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 28, 2028

Study Registration Dates

• First Submitted: June 17, 2025
• First Submitted That Met QC Criteria: August 1, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CFTR modulators; Cystic Fibrosis Related Diabetes; cystic fibrosis transmembrane conductance regulator (CFTR); Elexacaftor/ tezacaftor/ivacaftor or ETI
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: IRB300014949; P30DK072482 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared, however cumulative data from all participants will be made available on completion of study as per NIH data sharing policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No