Verapamil Effect in Cystic Fibrosis-related Dysglycemia

Prior treatment

• Treatment with IV antibiotics for a CF exacerbation within 1 month
• History of previously diagnosed vasovagal syncopal episodes related to hypotension
• Need for the use of any pertinent medications (beta blockers, carbamazepine, phenobarbital, phenytoin, HMG-CoA reductase inhibitors, lithium, theophylline, clonidine).

Other illness

• Severe lung disease indicated by forced expiratory volume in 1 second (FEV1) \<50% predicted on most recent spirometry testing
• Known hypersensitivity to verapamil
• History of significant cardiac disease (e.g. severe ventricular dysfunction, hypertrophic cardiomyopathy)
• History of certain arrhythmias (e.g. AV block, accessory pathway such as Wolff-Parkinson-White or Lown-Ganong-Levine syndromes)
• End stage renal disease on dialysis
• History of Duchenne's muscular dystrophy
• Allergy to any of the components of the MMTT standardized meal

Lab values

• Most recent HbA1c \>7%
• Abnormal liver function tests defined as AST or ALT \>1.5 upper limit of normal \[ULN\] at the time of screening, or end stage cirrhosis

Age

• Blood pressure (BP) \<90/60 (adults) or \<5th centile for age and gender (youth) in 2 out of 3 measurements
• Heart rate (HR) \<60 bpm (adults) or \<2nd centile for age and gender (youth) in 2 out of 3 measurements

Other

• Body mass index (BMI) \<18 kg/m2
• Weight \<50 kg
• Current or planned pregnancy within the next 6 months
• Systemic supraphysiologic glucocorticoid use within 1 month
• Initiation or discontinuation of a CFTR modulator within 3 months (i.e. recent change in CFTR modulator formulation/usage)
• Current use of insulin, a GLP-1 receptor agonist, or oral anti-diabetic agent
• Not taking a CFTR modulator due to genotype-ineligibility
• Current use of vanzacaftor/tezacaftor/deutivcaftor

• Age 14 years and older
• Genetically-confirmed diagnosis of cystic fibrosis
• Clinical diagnosis of pancreatic insufficiency, defined as requiring pancreatic enzyme replacement therapy (PERT)
• Diagnosis of AGT or CFRD within 3-months of study enrollment
  • AGT is defined as having either a OGTT 2-hour glucose \>140 mg/dL and \<200 mg/dL or OGTT 1-hour glucose \>200 mg/dL
  • CFRD is defined as having a fasting glucose \>126 mg/dL and/or OGTT 2-hour glucose \>200 mg/dL
• Willing to attempt to maximize verapamil to the goal study dosage of 360 mg PO daily
• If taking elexacaftor/tezacaftor/ivacaftor (ETI), willing to adjust dosing