Glucose Metabolism in Cystic Fibrosis Related Diabetes (CFRD)

The University of Alabama at Birmingham

Status: Begins enrollment in 1 month

Conditions: Cystic Fibrosis Related Diabetes

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT07102043

P30DK072482 (U.S. NIH Grant/Contract)

IRB300014949

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

30 participants in 2 patient groups

CFRD F508del +ETI

Description:

CFRD with at least one copy of F508del currently on elexacaftor/tezacaftor/ivacaftor (CFRDF508del+ETI),

CFRD-ETI

Description:

CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI).