학술논문
Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience.
Document Type
Academic Journal
Author
Ekhlaspour L; University of California, San Francisco, San Francisco, CA, USA.; Buckingham B; Stanford University, Palo Alto, CA, USA.; Bauza C; Jaeb Center for Health Research, Tampa, FL, USA.; Clements M; Children's Mercy Hospital-Kansas City, Kansas City, MO, USA.; Forlenza GP; Barbara Davis Center, University of Colorado Anschutz Medical Campus, Denver, CO, USA.; Neyman A; Indiana University School of Medicine, Indianapolis, IN, USA.; Norlander L; Stanford University, Palo Alto, CA, USA.; Schamberger M; Indiana University School of Medicine, Indianapolis, IN, USA.; Sherr JL; Yale School of Medicine, New Haven, CT, USA.; Bailey R; Jaeb Center for Health Research, Tampa, FL, USA.; Beck RW; Jaeb Center for Health Research, Tampa, FL, USA.; Kollman C; Jaeb Center for Health Research, Tampa, FL, USA.; Beasley S; University of Minnesota, Minneapolis, MN, USA.; Cobry E; Barbara Davis Center, University of Colorado Anschutz Medical Campus, Denver, CO, USA.; DiMeglio LA; Indiana University School of Medicine, Indianapolis, IN, USA.; Paprocki E; Children's Mercy Hospital-Kansas City, Kansas City, MO, USA.; Van Name M; Yale School of Medicine, New Haven, CT, USA.; Moran A; University of Minnesota, Minneapolis, MN, USA.
Source
Publisher: Elsevier Inc Country of Publication: Netherlands NLM ID: 101629335 Publication Model: eCollection Cited Medium: Internet ISSN: 2214-6237 (Electronic) Linking ISSN: 22146237 NLM ISO Abbreviation: J Clin Transl Endocrinol Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D.
Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team.
Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event.
Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ekhlaspour receives salary support from NIH and research support from JDRF. She reports receiving consulting fees from Medtronic, Tandem Diabetes Care and Ypsomed; receiving speaking fees from Insulet; and receiving research support from Medtronic, MannKind and Abbot through her institution. Her prior institution has received research support from Medtronic, Tandem Diabetes Care, Insulet, Dexcom and Beta Bionics. Dr. Buckingham reports receiving grants, personal fees, and/or nonfinancial support from Medtronic, Tandem Diabetes Care, Insulet, NovoNordisk, and Lilly and reports his institution has received research funding from Medtronic, Tandem Diabetes Care, Beta Bionics, and Insulet. Dr. Bauza reports no disclosures. Dr. Clements reports receiving personal fees from Glooko Inc and nonfinancial support from Dexcom and Abbott Diabetes Care. Dr. Forlenza reports serving as a consultant, speaker or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics and reports his institution has received funding on his behalf for research grants from Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics. Dr. Neyman reports no disclosures. Dr. Norlander reports no disclosures. Dr. Schamberger reports no disclosures. Dr. Sherr reported receiving speaking honoraria from Lilly, Insulet, Medtronic, and Zealand Pharma; serving on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, JDRF (formally the Juvenile Diabetes Research Foundation) T1D Fund, StartUp Health T1D Moonshot, and Vertex Pharmaceuticals; receiving consultant fees from Insulet and Medtronic; and reported that her institution has received research grant support from Medtronic and Insulet. Mr. Bailey reports no disclosures. Dr. Beck reports his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; grant funding from Bigfoot Biomedical; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Lilly and NovoNordisk; and consulting fees from Insulet and Zucara Therapeutics. Dr. Kollman reports receiving grants from Dexcom and Tandem Diabetes Care. Ms. Beasley reports no disclosures. Dr. Cobry reports no disclosures. Dr. DiMeglio reports receiving consulting or advisory fees from Abata Therapeutics, MannKind, Provention Bio, and Zealand Pharma and study supplies from Dexcom. Dr. Paprocki reports no disclosures. Dr. Van Name reports receiving research support from ProventionBio. Dr. Moran reports serving on advisory boards from Dompé Farmaceutici SpA, ProventionBio, and Abata Therapeutics; serving on a data and safety monitoring board for NovoNordisk; and reported that her institution has received grant funding on her behalf from Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences and study supplies from NovoNordisk, Medtronic, and Abbott Diabetes.
(© 2024 The Authors.)
Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team.
Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event.
Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ekhlaspour receives salary support from NIH and research support from JDRF. She reports receiving consulting fees from Medtronic, Tandem Diabetes Care and Ypsomed; receiving speaking fees from Insulet; and receiving research support from Medtronic, MannKind and Abbot through her institution. Her prior institution has received research support from Medtronic, Tandem Diabetes Care, Insulet, Dexcom and Beta Bionics. Dr. Buckingham reports receiving grants, personal fees, and/or nonfinancial support from Medtronic, Tandem Diabetes Care, Insulet, NovoNordisk, and Lilly and reports his institution has received research funding from Medtronic, Tandem Diabetes Care, Beta Bionics, and Insulet. Dr. Bauza reports no disclosures. Dr. Clements reports receiving personal fees from Glooko Inc and nonfinancial support from Dexcom and Abbott Diabetes Care. Dr. Forlenza reports serving as a consultant, speaker or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics and reports his institution has received funding on his behalf for research grants from Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics. Dr. Neyman reports no disclosures. Dr. Norlander reports no disclosures. Dr. Schamberger reports no disclosures. Dr. Sherr reported receiving speaking honoraria from Lilly, Insulet, Medtronic, and Zealand Pharma; serving on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, JDRF (formally the Juvenile Diabetes Research Foundation) T1D Fund, StartUp Health T1D Moonshot, and Vertex Pharmaceuticals; receiving consultant fees from Insulet and Medtronic; and reported that her institution has received research grant support from Medtronic and Insulet. Mr. Bailey reports no disclosures. Dr. Beck reports his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; grant funding from Bigfoot Biomedical; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Lilly and NovoNordisk; and consulting fees from Insulet and Zucara Therapeutics. Dr. Kollman reports receiving grants from Dexcom and Tandem Diabetes Care. Ms. Beasley reports no disclosures. Dr. Cobry reports no disclosures. Dr. DiMeglio reports receiving consulting or advisory fees from Abata Therapeutics, MannKind, Provention Bio, and Zealand Pharma and study supplies from Dexcom. Dr. Paprocki reports no disclosures. Dr. Van Name reports receiving research support from ProventionBio. Dr. Moran reports serving on advisory boards from Dompé Farmaceutici SpA, ProventionBio, and Abata Therapeutics; serving on a data and safety monitoring board for NovoNordisk; and reported that her institution has received grant funding on her behalf from Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences and study supplies from NovoNordisk, Medtronic, and Abbott Diabetes.
(© 2024 The Authors.)