Cystic Fibrosis Clinical Trial
Official title:
A Randomized, Double-blind, Crossover Clinical Trial of Metformin in Those With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function
The purpose of this study is to assess the efficacy of metformin to improve airway ion channel function in those with CF-related diabetes (CFRD)
Status | Recruiting |
Enrollment | 36 |
Est. completion date | October 1, 2025 |
Est. primary completion date | May 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion criteria: 1. Age >18 years with a prior diagnosis of CF. 2. Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor for 30 days prior to day 0 3. 3. Diagnosis of CFRD with evidence of continued glucose intolerance at least 6 months after starting elexacaftor/tezacaftor/ivacaftor 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 |
Country | Name | City | State |
---|---|---|---|
United States | University of Kansas Medical Center | Kansas City | Kansas |
Lead Sponsor | Collaborator |
---|---|
University of Kansas Medical Center |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in BK channel gene expression | Levels of LRRC26 (big potassium channel regulatory subunit) mRNA will be measured by polymerase chain reaction from nasal cells acquired via brushing | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in BK function, as measured by nasal potential difference testing | Nasal potential difference testing measures direct BK current in the nasal epithelium, with greater current indicating greater BK function | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in receptor for receptor for advanced glycation end products (RAGE) gene expression | Levels of RAGE mRNA will be measured by polymerase chain reaction from nasal cells acquired via brushing | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in advanced glycation end products (AGE) | Plasma levels of AGE, receptor for AGE (RAGE), soluble RAGE and S100A12 will be quantified by ELISA | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in sweat chloride | Measured as a secondary marker of CFTR function, with lower levels indicating greater CFTR function | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in lung function | Measured by percent predicted forced expiatory volume in one second captured on spirometry (FEV1) | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in Quality of Life (CFQ-R) | Measured by Patient Reported Outcome measurement tool called CFQ-R (validated) | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Change in airway inflammatory markers | Inflammatory markers (interleukin-1beta, interleukin-6, interleukin-8, transforming growth factor beta1, tissue necrosis factor-alpha, matrix metalloproteinase-9 and cyclooxygenase-2) collected from nasal fluid will be measured by enzyme linked immunosorbent assay (ELISA) | Baseline through week 14 and week 16 through week 30 of metformin treatment | |
Secondary | Safety of metformin | Number of adverse events during study period | Baseline through week 30 of metformin treatment | |
Secondary | Pharmacokinetics of metformin | Plasma levels of metformin will be quantified by liquid chromatography-mass spectrometry | Week 14 and week 30 of metformin treatment |
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