Acetazolamide for Type 1 Diabetes

Overseen By Todd May, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

Must be taking: Insulin

Must not be taking: Diuretics

Disqualifiers: Liver disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of acetazolamide for individuals with Type 1 Diabetes. Participants will test various doses to assess the drug's impact on kidney function. This offers an opportunity to contribute to research that could enhance diabetes treatment. The trial seeks individuals with Type 1 Diabetes who have maintained a stable medication plan for at least three months. As a Phase 1 and Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain types of diuretics (medications that help remove excess water from the body). It's best to discuss your current medications with the study team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that low doses of acetazolamide are generally safe for people with type 1 diabetes. This medication has been used for various health issues, providing some knowledge about its safety. The trial tests doses of 62.5mg, 125mg, and 250mg taken twice a day, which are lower than the usual maximum daily dose of 1 gram used for other purposes.

Although acetazolamide's safety and effectiveness are not fully confirmed for everyone, past studies have found it mostly safe in adults. Common side effects might include a change in taste or mild dizziness, but serious problems are rare. Given its long history of use, the medication's safety record is encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about acetazolamide for type 1 diabetes because it offers a unique approach compared to traditional treatments like insulin therapy. Unlike insulin, which directly regulates blood sugar levels, acetazolamide is known for its ability to reduce blood pressure and has diuretic properties that may impact glucose regulation and insulin sensitivity indirectly. This novel mechanism of action could provide additional benefits in managing diabetes-related complications. Moreover, acetazolamide is administered in varying doses (62.5mg, 125mg, and 250mg), potentially allowing for tailored treatment options to fit individual patient needs better.

What evidence suggests that acetazolamide might be an effective treatment for Type 1 Diabetes?

Research has shown that acetazolamide can lower the glomerular filtration rate (GFR) in people with type 1 diabetes. However, studies have found this decrease in GFR to be temporary and not to affect blood sugar levels. Acetazolamide might help manage kidney function by reducing glomerular hyperfiltration, a condition where the kidneys filter too much blood, common in type 1 diabetes. Early research suggests that different doses of acetazolamide, which participants in this trial may receive, can achieve this without affecting sugar processing. This could potentially help protect kidney function in people with type 1 diabetes. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with Type 1 Diabetes who have been on a stable medication regimen for at least 3 months, have an eGFR of ≥45 ml/min/1.73m2, and are not using certain diuretics or other exclusionary medications. Women must be non-childbearing or use two contraception methods; men need to use contraception too.

Inclusion Criteria

I agree to use two forms of birth control during the study.

I have Type 1 Diabetes and have been on a stable medication plan for over 3 months.

Your kidney function, measured by eGFR, is at least 45ml/min/1.73m2.

Exclusion Criteria

I have liver disease, drink more than 14 alcoholic beverages a week, or have high liver enzyme levels.

I have not been hospitalized in the last 60 days.

I am taking water pills for my health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive escalating doses of acetazolamide, each for a 2-week dosing period followed by a 2-week washout period

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide

Trial Overview

The study tests different doses of acetazolamide (62.5mg, 125mg, and 250mg twice daily) in escalating order with washout periods between each dose. Participants will undergo kidney function tests before and after each dosing period over approximately 16 weeks.

How Is the Trial Designed?

Group I: Acetazolamide - 62.5mg Dose Experimental Treatment 1 Intervention

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

Group II: Acetazolamide - 250mg Dose Experimental Treatment 1 Intervention

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

Group III: Acetazolamide - 125mg Dose Experimental Treatment 1 Intervention

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

Acetazolamide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

Approved in European Union as Diamox for:

• Glaucoma
• Epilepsy
• Edema

Approved in Canada as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

JDRF

Collaborator

Trials

4

Recruited

50,100+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Published Research Related to This Trial

Sulfonylureas remain a relevant option for blood glucose management in type 2 diabetes, despite the rise of newer incretin-based therapies, according to recent international guidelines.

When prescribing sulfonylureas, it's crucial to choose the right medication, such as gliclazide or glimepiride for patients with normal kidney function, and to educate patients on using the lowest effective dose for optimal glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sulfonylureas in today's blood glucose lowering therapy. New data on advantages and potential barriers of an "old" antidiabetic group]. Winkler, G.[2015]

Second-generation sulfonylureas, like glyburide and glipizide, are more potent than first-generation drugs due to their lipophilic properties, allowing for effective hypoglycemic therapy at lower serum concentrations.

These newer sulfonylureas not only stimulate insulin secretion but also enhance insulin's effects on muscle, fat, and liver cells, potentially by increasing the number of insulin receptors, making them a safer option when used with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of sulfonylureas. Skillman, TG., Feldman, JM.[2019]

Acetazolamide (AZM) increased insulin release from isolated pancreatic islets at low glucose levels but decreased it at high glucose levels, suggesting a complex role in insulin regulation depending on glucose concentration.

In vivo studies showed that AZM administration led to increased serum insulin levels and transient hyperglycemia in fed mice, while also causing decreased glucose tolerance and providing protection against alloxan toxicity, indicating potential therapeutic effects and mechanisms involving carbonic anhydrase inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on insulin release, serum glucose and insulin, glucose tolerance, and alloxan sensitivity of mice. Boquist, L., Bäckman, AM., Strömberg, C.[2018]

There were three cases where acetohexamide was mistakenly given instead of acetazolamide due to their similar appearance and names, highlighting a significant risk for medication errors.

One patient experienced a severe hypoglycemic reaction leading to head trauma and confusion, which required emergency hospitalization, demonstrating the potential dangers of such medication mix-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inadvertent substitution of acetohexamide for acetozolamide. Hargett, NA., Ritch, R., Mardirossian, J., et al.[2019]

A 66-year-old woman experienced irreversible anaphylactic shock and severe pulmonary edema after being prescribed acetazolamide for glaucoma, likely due to a cross-reaction with her known sulphonamide allergy.

This case highlights the critical importance of screening for sulphonamide allergies before prescribing acetazolamide, as such allergies should be considered a contraindication due to the chemical similarities between the two drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. Gerhards, LJ., van Arnhem, AC., Holman, ND., et al.[2017]

In a pilot study involving 15 patients with cystoid macular edema, acetazolamide demonstrated a significant therapeutic effect, with 14 out of 20 eyes showing reduced edema and improved visual acuity as confirmed by fluorescein angiography.

No serious side effects were reported during the treatment, indicating that acetazolamide is a safe option for managing cystoid macular edema, although the study suggests that earlier intervention may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of cystoid diffuse macular edema after uveitis and cataract surgery with the carbonic anhydrase inhibitor acetazolamide (Diamox)]. Schilling, H., Pauleikhoff, D., Schrenk, M., et al.[2013]

In a study involving rats, a daily oral dose of acetazolamide (1 mg for five days) did not affect tear production but significantly reduced lacrimal peroxidase secretion by 60%.

The decrease in peroxidase secretion was reversible, returning to baseline levels after stopping the medication, indicating a temporary effect on lacrimal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of acetazolamide (Diamox) on tear secretion. van Agtmaal, EJ., Thörig, L., van Haeringen, NJ.[2019]

Generic acetazolamide and brand-name acetazolamide (Diamox) have equivalent effects on lowering intraocular pressure and achieve comparable blood levels after a single dose.

The cost of generic acetazolamide is 37% lower than that of the brand-name version, and food intake does not affect the absorption of acetazolamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of generic acetazolamide. Ellis, PP., Price, PK., Kelmenson, R., et al.[2019]

The newly synthesized hydrazinecarbothioamides, particularly compounds 5a and 5c, demonstrated significant antihyperglycemic effects in diabetic mice, lowering blood glucose levels to around 103.3 and 102 mg/dl, respectively.

These compounds also reduced oxidative stress markers by decreasing malondialdehyde levels and normalizing glutathione levels, suggesting their potential as effective treatments for managing diabetes-related oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and synthesis of hydrazinecarbothioamide sulfones as potential antihyperglycemic agents. Aly, AA., Hassan, AA., Makhlouf, MM., et al.[2021]

(R)-acetoxyhexamide (R-ACX) effectively stimulates insulin release from pancreatic beta-cells and lowers blood glucose levels in fasted rats in a dose-dependent manner, indicating its potential as a hypoglycemic agent.

The hypoglycemic effect of (R)-ACX is rapid and short-lasting, which may be beneficial for controlling postprandial hyperglycemia in patients with non-insulin-dependent diabetes mellitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity. Seri, K., Sanai, K., Kurashima, K., et al.[2019]

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