An Open Label Clinical Trial of Metformin in Those With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in BK channel gene expression
研究概览
简要总结
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)
详细描述
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. There will be a dose-escalation 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 for 14 weeks. 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years with a prior diagnosis of CF.
- •Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor or vanzacaftor/tezacaftor/deutivacaftor for 30 days prior to day 0
- •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:
- •Insulin use
- •Hemoglobin A1C >6.5%
- •Fasting glucose >126 mg/dl
- •Non-fasting glucose >200 mg/dl (random or as part of a 2-hr OGTT)
排除标准
- •Prior lung or liver transplant
- •Use of supplemental oxygen
- •CF pulmonary exacerbation requiring hospitalization or intravenous antibiotics in the preceding 30 days
- •Systemic corticosteroid or regular non-steroidal anti-inflammatory use in the preceding 30 days
- •Cardiac, renal (creatinine clearance <45 mL/minute), neurologic, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study
- •Alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase >1.5X the upper limit of normal; bilirubin >3 mg/dL
- •Taking medications that interact with metformin.
- •Vitamin B12 deficiency
- •Pregnancy or lactation
- •Inability or unwillingness to comply with an approved contraceptive method during the study period (females of childbearing age)
- •Use of medications known to be strong CYP inducers or moderate to strong CYP inhibitors
- •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
- •Participation in another interventional trial that, in the opinion of the investigator, has the potential to affect the primary outcome
研究组 & 干预措施
Metformin dose regimen A
patients with CFRD on highly effective CFTR modulator therapy who meet criteria and agree to participation in the study will be placed on metformin. There will be a dose-escalation 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 for 14 weeks.
干预措施: Metformin Hydrochloride (Drug)
结局指标
主要结局
Change in BK channel gene expression
时间窗: Baseline through week 14 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
次要结局
- Change in BK function, as measured by nasal potential difference testing(Baseline through week 14 of metformin treatment)
- Change in receptor for receptor for advanced glycation end products (RAGE) gene expression(Baseline through week 14 of metformin treatment)
- Change in advanced glycation end products (AGE)(Baseline through week 14 of metformin treatment)
- Change in sweat chloride(Baseline through week 14 of metformin treatment)
- Change in lung function(Baseline through week 14 of metformin treatment)
- Change in Quality of Life (CFQ-R)(Baseline through week 14 of metformin treatment)
- Change in airway inflammatory markers(Baseline through week 14 of metformin treatment)
- Safety of metformin(Baseline through week 14 of metformin treatment)
- Pharmacokinetics of metformin(Week 14 of metformin treatment)
研究者
Matthias Salathe, MD
Professor
University of Kansas Medical Center