Metformin's effects on lung function in patients with cystic fibrosis-related diabetes

An Open Label Clinical Trial of Metformin in Those With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function

This study is testing if metformin can help improve lung function in people with cystic fibrosis-related diabetes by giving them different doses of the medication over 14 weeks.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (Academic / other)
• Locations: 1 site (Kansas City, Kansas)
• Trial ID: NCT04530383 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of metformin in improving airway ion channel function in patients diagnosed with cystic fibrosis-related diabetes (CFRD). Up to 30 eligible participants will be randomized to receive either a low or normal dose of metformin, with a crossover design allowing each participant to experience both dosing regimens over a 14-week period. A placebo will be used to ensure that participants are unaware of which treatment they are receiving. Additionally, to mitigate the risk of vitamin B12 deficiency associated with metformin, participants will receive a daily supplement of cyanocobalamin throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years old with a diagnosis of cystic fibrosis and CFRD who have been on specific CFTR modulator therapies.

Not a fit: Patients with prior lung or liver transplants, those requiring supplemental oxygen, or individuals with certain comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved lung function and overall health for patients with cystic fibrosis-related diabetes.

How similar studies have performed: While the use of metformin in this specific context is novel, previous studies have shown potential benefits of metformin in other diabetic conditions.

Eligibility criteria

Inclusion criteria:

1. Age \>18 years with a prior diagnosis of CF.
2. Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor or vanzacaftor/tezacaftor/deutivacaftor for 30 days prior to day 0
3. Diagnosis of CFRD with evidence of continued glucose intolerance at least 6 months after starting qualifying modulator therapy will be based upon one of the following:

   1. Insulin use
   2. Hemoglobin A1C \>6.5%
   3. Fasting glucose \>126 mg/dl
   4. Non-fasting glucose \>200 mg/dl (random or as part of a 2-hr OGTT)

Exclusion criteria:

1. Prior lung or liver transplant
2. Use of supplemental oxygen
3. BMI \<18
4. CF pulmonary exacerbation requiring hospitalization or intravenous antibiotics in the preceding 30 days
5. Systemic corticosteroid or regular non-steroidal anti-inflammatory use in the preceding 30 days
6. Cardiac, renal (creatinine clearance \<45 mL/minute), neurologic, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study
7. Alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase \>1.5X the upper limit of normal; bilirubin \>3 mg/dL
8. Taking medications that interact with metformin.
9. Vitamin B12 deficiency
10. Pregnancy or lactation
11. Inability or unwillingness to comply with an approved contraceptive method during the study period (females of childbearing age)
12. Use of medications known to be strong CYP inducers or moderate to strong CYP inhibitors
13. In the opinion of the investigator any severe or acute or chronic condition or laboratory abnormality that may increase the risk associated with trial participation or make the subject inappropriate for enrollment
14. Participation in another interventional trial that, in the opinion of the investigator, has the potential to affect the primary outcome

Where this trial is running

Kansas City, Kansas

• University of Kansas Medical Center — Kansas City, Kansas, United States (Recruiting)

Study contacts

• Principal investigator: Matthias A Salathe, M.D. — Professor
• Study coordinator: Matthias A Salathe, M.D.

Conditions Cystic Fibrosis-related Diabetes; Cystic Fibrosis; Metformin