Acetazolamide in Persons With Type 1 Diabetes - Dose Finding

NCT05473364 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: UC-MEDJP-05
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Keywords

acetazolamide

Outcome Measures

Primary Outcomes (3)

• Change in mGFR percent

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

  2 Weeks

• Preservation of Serum Bicarbonate

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

  2 Weeks

• Preservation of Serum Potassium

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

  2 Weeks

Study Arms (3)

Acetazolamide - 62.5mg Dose

EXPERIMENTAL

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

Drug: Acetazolamide

Acetazolamide - 125mg Dose

EXPERIMENTAL

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

Drug: Acetazolamide

Acetazolamide - 250mg Dose

EXPERIMENTAL

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

Drug: Acetazolamide

Interventions

Acetazolamide DRUG

Diuretic and carbonic anhydrase inhibitor medication

Acetazolamide - 125mg Dose; Acetazolamide - 250mg Dose; Acetazolamide - 62.5mg Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

UC San Diego Altman Clinical & Translational Research Institute

La Jolla, California, 92037, United States

Location

Related Publications (1)

• Ginsberg C, Seegmiller JC, Vallon V, SeungMi Jin S, Thomas RL, Boeder SC, Pettus J, Ix JH. Acetazolamide Therapy and Kidney Function in Persons with Nonalbuminuric Diabetes Mellitus Type 1. J Am Soc Nephrol. 2025 Mar 1;36(3):463-470. doi: 10.1681/ASN.0000000515. Epub 2024 Oct 8.

  PMID: 39466253 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Escalating dose finding trial.

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: July 25, 2022
• Study Start: March 20, 2023
• Primary Completion: February 23, 2024
• Study Completion: July 31, 2024
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)