Effects of Metformin on Airway Ion Channel Dysfunction in Cystic Fibrosis-related Diabetes
- Conditions
- Cystic FibrosisCystic Fibrosis-related Diabetes
- Interventions
- Registration Number
- NCT04530383
- Lead Sponsor
- University of Kansas Medical Center
- Brief Summary
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)
- Detailed Description
Up to 30 patients with CFRD on highly effective CFTR modulator therapy who meet criteria and agree to participation in the study will be placed on metformin 500mg twice daily (low) and 1000mg twice daily (normal) in a randomized order (simple randomization). There will be a dose-escalation with each dosing regimen starting with 500mg twice daily for a week, followed by 500mg in the AM and 1000mg in the PM for another week and finally followed by 1000mg twice daily until the end of normal dose cycle (in those in the normal dose portion of the crossover trial). A matching placebo pill will be utilized so participants do not know which dosing regimen, low or normal, they are on during each 14-week period. Participants will continue each dosing regimen of metformin for 14 weeks with a washout period of 2 weeks between dose changes. To minimize risk of B12 deficiency, a known side effect of long-term metformin use, we will also provide a supplement of 1000 µg oral cyanocobalamin daily for the duration of the trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Metformin dose regimen A Metformin Hydrochloride Participants with CFRD on elexacaftor/tezacaftor/ivacaftor who meet criteria and agree to participation in the study will be placed on metformin 500 mg twice daily on study week 0 after undergoing study procedures through week 14. They will then undergo a two week washout period. For the second half of the study metformin will be resumed and, if tolerated, dose will be increased by 500mg on weeks 17 and 18 to a final dose of 1000 mg twice daily through end of study (week 30). Metformin dose regimen B Metformin Hydrochloride Participants with CFRD on elexacaftor/tezacaftor/ivafactor who meet criteria and agree to participation in the study will be placed on metformin 500 mg twice daily on study week 0 after undergoing study procedures. If tolerated, dose will be increased by 500mg on weeks 1 and 2 to a final dose of 1000 mg twice daily through week 14.They will then undergo a two week washout period. For the second half of the study metformin will be resumed at a dose of 500 mg twice daily through the end of study (week 30).
- Primary Outcome Measures
Name Time Method Change in BK channel gene expression Baseline through week 14 and week 16 through week 30 of metformin treatment Levels of LRRC26 (big potassium channel regulatory subunit) mRNA will be measured by polymerase chain reaction from nasal cells acquired via brushing
- Secondary Outcome Measures
Name Time Method Change in sweat chloride Baseline through week 14 and week 16 through week 30 of metformin treatment Measured as a secondary marker of CFTR function, with lower levels indicating greater CFTR function
Change in lung function Baseline through week 14 and week 16 through week 30 of metformin treatment Measured by percent predicted forced expiatory volume in one second captured on spirometry (FEV1)
Change in airway inflammatory markers Baseline through week 14 and week 16 through week 30 of metformin treatment 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)
Pharmacokinetics of metformin Week 14 and week 30 of metformin treatment Plasma levels of metformin will be quantified by liquid chromatography-mass spectrometry
Change in advanced glycation end products (AGE) Baseline through week 14 and week 16 through week 30 of metformin treatment Plasma levels of AGE, receptor for AGE (RAGE), soluble RAGE and S100A12 will be quantified by ELISA
Change in BK function, as measured by nasal potential difference testing Baseline through week 14 and week 16 through week 30 of metformin treatment Nasal potential difference testing measures direct BK current in the nasal epithelium, with greater current indicating greater BK function
Change in receptor for receptor for advanced glycation end products (RAGE) gene expression Baseline through week 14 and week 16 through week 30 of metformin treatment Levels of RAGE mRNA will be measured by polymerase chain reaction from nasal cells acquired via brushing
Change in Quality of Life (CFQ-R) Baseline through week 14 and week 16 through week 30 of metformin treatment Measured by Patient Reported Outcome measurement tool called CFQ-R (validated)
Safety of metformin Baseline through week 30 of metformin treatment Number of adverse events during study period
Trial Locations
- Locations (1)
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States