Open-label acetazolamide will be given to persons with type 1 diabetes to determine the optimal dose to be used in a dose finding trial design. Each dose of acetazolamide will be given for a 2-week period, followed by a 2-week washout period. The three doses examined will be open-label 62.5mg twice daily, 125mg twice daily, and 250mg twice daily of acetazolamide.~To measure mGFR (measured glomerular filtration rate), an Iohexol GFR procedure will be completed at the beginning and end of each treatment period. We will follow a standard protocol for the procedure that has been used in multiple studies. Iohexol (Omnipaque 300®) will be used in order to obtain a precise measure of mGRF throughout the course of the test. Iohexol will be prepared by the UCSD (University of California, San Diego) Investigational Drug Services at the ACTRI (Altman Clinical and Translation Research Institute) by drawing up 5mL into a syringe per standard pharmacy protocol. The iohexol will be dispensed to a nurse or research coordinator who will weigh the syringe prior to infusion and again after infusion to assess exact dosage delivered.~A study nurse will insert 1 IV (intravenous) line in the hand or arm for the infusion of iohexol. They will then insert a second IV in the opposite arm for blood collection. Serial blood draws will occur throughout the procedure relative to the time of iohexol infusion. A study nurse will infuse iohexol over a 1-2 minute period, flush with 10mL of normal saline and remove the IV. Blood samples will be collected at the following time points for mGFR analysis:~-5 minutes (prior to iohexol infusion)~2 hours (120 minutes post infusion)~4 hours (120 minutes post infusion)~6 hours (120 minutes post infusion)~Following completion and analysis of the dose finding trial, the optimal dose of acetazolamide will be chosen for a crossover trial based on the largest mean reduction in mGFR while avoiding a significant median reduction in sodium bicarbonate and/or potassium.
This is a dose finding trial where participants will receive escalating doses of acetazolamide, each for a 2-week dosing period followed by a 2-week washout period. The three doses examined will be open-label 62.5mg twice daily, 125mg twice daily, and 250mg twice daily of acetazolamide. A baseline Iohexol GFR (glomerular filtration rate) measurement will be performed prior to the first administration of each acetazolamide dose and then again following each dosing period. Including a screening visit and a follow-up visit, there will be a total of 8 study visits over approximately 16 weeks.