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Acetazolamide in Persons With Type 1 Diabetes

Primary Purpose

Type 1 Diabetes

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Acetazolamide

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring acetazolamide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and Females ≥ 18 years at the time of consent.
Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study.
Male subjects must be willing to use clinically acceptable method of contraception during the entire study.
Have a clinical diagnosis of Type 1 Diabetes on a stable medication regimen for at least 3 months.
eGFR (estimated glomerular filtration rate) ≥ 45ml/min/1.73m2
Serum bicarbonate ≥ 24 meq/L
Negative urine toxicology screen.
Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria:

History of allergic reaction to acetazolamide, another carbonic anhydrase inhibitor, or any of the inactive ingredients in the acetazolamide tablets.
Liver disease (clinical diagnosis of cirrhosis by imaging of physician; > 14 drinks/week; AST (aspartate aminotransferase), ALT (alanine aminotransferase), or total bilirubin > 2 times the upper limit of normal).
Serum hemoglobin A1c > 10.0%
Serum hemoglobin concentration of <8 g/dL.
Use of > 4 anti-hypertensives, or systolic blood pressure >160mm Hg at the screening visit.
Use of loop, thiazide or potassium sparing diuretics.
A medical condition requiring active surgical or medical intervention whose urgency would preclude participation in this study at the discretion of the site investigator {active cardiac or pulmonary conditions, ongoing ischemia or cardiac symptoms, uncorrected CAD (coronary artery disease) or decompensated CHF(congestive heart failure)}.
Institutionalized individual (prisoners, patients with signification mental illness, or nursing home residents).
Active pregnancy, breastfeeding, or planning to become pregnant during the study period.
Current participation in another clinical trial (observational studies are exempted).
In the opinion of the investigators, inability to adhere to the study medical regimen or comply with recommendations.
Inability or unwillingness to travel to study visits.
Life expectancy < 1 year.
Hospitalization within 60 days prior to screening.
A plan to leave the geographical area within 6 months.

Sites / Locations

UC San Diego Altman Clinical & Translational Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Acetazolamide - 62.5mg Dose

Acetazolamide - 125mg Dose

Acetazolamide - 250mg Dose

Arm Description

2-week treatment period with 62.5mg dose of acetazolamide taken twice daily.

2-week treatment period with 125mg dose of acetazolamide taken twice daily.

2-week treatment period with 250mg dose of acetazolamide taken twice daily.

Outcomes

Primary Outcome Measures

Change in mGFR percent

The change in mGFR percent from pre-dosing to post-treatment as measured by the iohexol procedure.

Preservation of Serum Bicarbonate

The preservation of serum bicarbonate concentrations at ≥ 22 meq/L from pre-dosing to post treatment.

Preservation of Serum Potassium

The preservation of serum potassium concentrations at ≥ 3.2 meq/L from pre-dosing to post treatment.

Secondary Outcome Measures

Full Information

NCT ID

NCT05473364

First Posted

July 22, 2022

Last Updated

March 21, 2023

Sponsor

University of California, San Diego

Collaborators

Juvenile Diabetes Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT05473364

Brief Title

Acetazolamide in Persons With Type 1 Diabetes

Official Title

Acetazolamide and Tubuloglomerular Feedback in Persons With Type 1 Diabetes: A Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 20, 2023 (Actual)

Primary Completion Date

November 30, 2025 (Anticipated)

Study Completion Date

May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Diego

Collaborators

Juvenile Diabetes Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

Keywords

acetazolamide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Model Description

Escalating dose finding trial.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Acetazolamide - 62.5mg Dose

Arm Type

Experimental

Arm Description

2-week treatment period with 62.5mg dose of acetazolamide taken twice daily.

Arm Title

Acetazolamide - 125mg Dose

Arm Type

Experimental

Arm Description

2-week treatment period with 125mg dose of acetazolamide taken twice daily.

Arm Title

Acetazolamide - 250mg Dose

Arm Type

Experimental

Arm Description

2-week treatment period with 250mg dose of acetazolamide taken twice daily.

Intervention Type

Drug

Intervention Name(s)

Acetazolamide

Intervention Description

Diuretic and carbonic anhydrase inhibitor medication

Primary Outcome Measure Information:

Title

Change in mGFR percent

Description

The change in mGFR percent from pre-dosing to post-treatment as measured by the iohexol procedure.

Time Frame

2 Weeks

Title

Preservation of Serum Bicarbonate

Description

The preservation of serum bicarbonate concentrations at ≥ 22 meq/L from pre-dosing to post treatment.

Time Frame

2 Weeks

Title

Preservation of Serum Potassium

Description

The preservation of serum potassium concentrations at ≥ 3.2 meq/L from pre-dosing to post treatment.

Time Frame

2 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and Females ≥ 18 years at the time of consent. Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study. Male subjects must be willing to use clinically acceptable method of contraception during the entire study. Have a clinical diagnosis of Type 1 Diabetes on a stable medication regimen for at least 3 months. eGFR (estimated glomerular filtration rate) ≥ 45ml/min/1.73m2 Serum bicarbonate ≥ 24 meq/L Negative urine toxicology screen. Able to provide written informed consent approved by an Institutional Review Board (IRB). Exclusion Criteria: History of allergic reaction to acetazolamide, another carbonic anhydrase inhibitor, or any of the inactive ingredients in the acetazolamide tablets. Liver disease (clinical diagnosis of cirrhosis by imaging of physician; > 14 drinks/week; AST (aspartate aminotransferase), ALT (alanine aminotransferase), or total bilirubin > 2 times the upper limit of normal). Serum hemoglobin A1c > 10.0% Serum hemoglobin concentration of <8 g/dL. Use of > 4 anti-hypertensives, or systolic blood pressure >160mm Hg at the screening visit. Use of loop, thiazide or potassium sparing diuretics. A medical condition requiring active surgical or medical intervention whose urgency would preclude participation in this study at the discretion of the site investigator {active cardiac or pulmonary conditions, ongoing ischemia or cardiac symptoms, uncorrected CAD (coronary artery disease) or decompensated CHF(congestive heart failure)}. Institutionalized individual (prisoners, patients with signification mental illness, or nursing home residents). Active pregnancy, breastfeeding, or planning to become pregnant during the study period. Current participation in another clinical trial (observational studies are exempted). In the opinion of the investigators, inability to adhere to the study medical regimen or comply with recommendations. Inability or unwillingness to travel to study visits. Life expectancy < 1 year. Hospitalization within 60 days prior to screening. A plan to leave the geographical area within 6 months.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Todd May, MS

Phone

858-246-2169

tmay@ucsd.edu

Facility Information:

Facility Name

UC San Diego Altman Clinical & Translational Research Institute

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Todd May, MS

tmay@ucsd.edu

12. IPD Sharing Statement

Plan to Share IPD

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Acetazolamide in Persons With Type 1 Diabetes

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