Acetazolamide for Schizophrenia

(APTS Trial)

Recruiting at 2 trial locations

Overseen By Vinayak Sant, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vishwajit Nimgaonkar, MD PhD

Must be taking: Antipsychotics

Disqualifiers: Substance abuse, Epilepsy, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether acetazolamide, a medication, can improve symptoms in people with schizophrenia when added to their usual treatment. Schizophrenia often includes symptoms like hearing voices or having unusual thoughts, and the trial aims to determine if acetazolamide can alleviate these. Participants will receive either acetazolamide or a placebo (a pill with no active medicine) to compare effects. Individuals who have been on a stable dose of antipsychotic medication for over a month and still experience strong symptoms might be suitable candidates. As a Phase 1, Phase 2 trial, this 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?

No, you will not have to stop taking your current antipsychotic medication. The trial requires that you continue your stable dose of antipsychotic drugs throughout the study.

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

Research has shown that acetazolamide has been tested for safety in various situations. In past studies involving individuals with psychosis, acetazolamide was generally well-tolerated, with most participants not experiencing serious side effects.

In another study involving 50 patients with bipolar disorder, many of whom faced severe mood issues like mania or depression, most tolerated the treatment well without serious problems.

Although acetazolamide is not yet approved specifically for schizophrenia, its use in other conditions suggests it might be safe. However, treatments can affect people differently. It is important to consult a healthcare professional before starting a new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Researchers are excited about acetazolamide for schizophrenia because it offers a novel approach compared to current antipsychotic treatments. While most treatments for schizophrenia target dopamine receptors to manage symptoms, acetazolamide works differently by influencing carbonic anhydrase enzymes. This unique mechanism could provide an alternative for individuals who do not respond well to traditional antipsychotics. Additionally, acetazolamide's potential role in modulating brain chemistry might lead to benefits beyond symptom control, such as improving cognitive function.

What evidence suggests that acetazolamide might be an effective treatment for schizophrenia?

Research suggests that acetazolamide, which participants in this trial may receive, might help people with schizophrenia. One study found it worked well, especially for certain types of schizophrenia, but it was less effective for unusual cases. Another source highlights its use in adults whose schizophrenia doesn't respond to standard treatments, noting it can be added to help when regular medications aren't enough. The main goal is to manage symptoms like seeing or hearing things that aren't there. While more research is needed, these early findings are promising for acetazolamide as a supportive treatment option. ^{1 2 3 6 7}

Who Is on the Research Team?

Vishwajit L Nimgaonkar, M.D., Ph.D.

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with treatment-resistant schizophrenia, having a PANSS score over 60 and significant positive symptoms despite medication. Participants must not be in another study, have taken acetazolamide before, or have certain medical conditions like epilepsy or substance abuse issues.

Inclusion Criteria

My schizophrenia symptoms remain severe despite treatment.

I have been on a stable dose of my antipsychotic medication for over a month.

Not participating in another randomized controlled clinical trial (RCT).

Exclusion Criteria

You have used illegal drugs or abused prescription drugs within the past month, or have had a drug addiction within the past 6 months (excluding nicotine).

I have a condition like epilepsy that could make my health unstable.

I am not allergic to ACZ and do not have renal acidosis, Addison's disease, or chronic glaucoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjunctive Acetazolamide or placebo added to prescribed antipsychotic drugs for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Placebo

Trial Overview The trial tests if acetazolamide can help people whose schizophrenia doesn't respond to usual drugs. It's a double-blind study, meaning neither the patients nor doctors know who gets the real drug versus a placebo (a harmless pill).

How Is the Trial Designed?

Group I: Acetazolamide Active Control 1 Intervention

acetazolamide capsules

Group II: Placebo Active Control 1 Intervention

Identical gelatin capsules

Who Is Running the Clinical Trial?

Vishwajit Nimgaonkar, MD PhD

Lead Sponsor

Trials

2

Recruited

220+

Stanley Medical Research Institute

Collaborator

Trials

141

Recruited

10,400+

Published Research Related to This Trial

Acetazolamide is effective in preventing acute mountain sickness, significantly reducing symptoms like headache and nausea, and its benefits are linked to increased arterial oxygen levels and reduced fluid retention.

While Acetazolamide can help treat established acute mountain sickness by improving oxygen levels, there is limited data on its effectiveness compared to other treatments like steroids or calcium channel blockers, and faster alternatives like Methazolamide may be more suitable in emergencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide and high altitude diseases. Bradwell, AR., Wright, AD., Winterborn, M., et al.[2013]

Topical dorzolamide significantly reduces intraocular pressure (IOP) in pediatric glaucoma patients, but it is less effective than oral acetazolamide, with an average IOP reduction of 27.4% compared to 35.7% for acetazolamide.

In a study of 11 patients, all experienced an increase in IOP when switched from acetazolamide to dorzolamide, indicating that while dorzolamide is a viable alternative, it may not provide sufficient control for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma. Portellos, M., Buckley, EG., Freedman, SF.[2019]

In a study involving nine patients with ocular hypertension, acetazolamide effectively reduced intraocular pressure (IOP) by 30% to 35%, with the most significant response observed at a 63 mg dose, which lowered IOP by an average of 8.2 mm Hg.

Higher doses of acetazolamide (up to 500 mg) did not produce a proportionally greater reduction in IOP, indicating that a 63 mg dose is sufficient for effective treatment, as it achieves similar results to higher doses without the need for increased plasma levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term dose response characteristics of acetazolamide in man. Friedland, BR., Mallonee, J., Anderson, DR.[2019]

In a study involving 11 patients, acetazolamide (Diamox) significantly increased blood flow in areas affected by thalamic and crossed cerebellar diaschisis, indicating its potential to enhance vascular response in these regions.

The results suggest that Diamox may lead to increased arteriolar dilation and improved perfusion in damaged brain areas, which could be beneficial for recovery or treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide effect on vascular response in areas with diaschisis as measured by Tc-99m HMPAO brain SPECT. Matsuda, H., Tsuji, S., Sumiya, H., et al.[2019]

In a study using baboon models, the two different radio-tracers, 99mTc-HMPAO and 123I-iodoamphetamine (123I(IMP)), showed expected differences in cerebral blood flow measurements without the drug acetazolamide.

Acetazolamide significantly enhanced the uptake of 123I(IMP) compared to 99mTc-HMPAO, suggesting that 123I(IMP) may provide better diagnostic information when assessing cerebrovascular reserve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP). Dormehl, IC., Oliver, DW., Hugo, N., et al.[2019]

The study used the 133Xe-DSPECT technique to measure regional cerebral blood flow (rCBF) in 32 healthy patients before and after administration of acetazolamide (Diamox), finding that a 1 g dose increased rCBF from 58 to 73 ml/100 g/min, indicating its efficacy in enhancing blood flow.

The research suggests that measuring both resting rCBF and the increase in rCBF (reserve capacity) can help differentiate between healthy individuals and those with reversible cerebrovascular disease, especially in patients with lower baseline rCBF values.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[133Xe-DSPECT: normal values of resting cerebral blood flow and reserve capacity]. Kreisig, T., Schmiedek, P., Leinsinger, G., et al.[2015]

In a study of 100 geriatric patients undergoing cataract surgery, those premedicated with dixyrazine experienced higher levels of anxiety compared to those given diazepam, indicating that dixyrazine may not be as effective for anxiety management in this context.

Patients receiving dixyrazine required more frequent intravenous sedatives than those on diazepam, suggesting that while dixyrazine can be used for mild sedation, it may not be suitable for patients needing more significant anxiety control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dixyrazine premedication for cataract surgery. A comparison with diazepam. Oikkonen, M., Heine, H., Salminen, U., et al.[2019]

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]

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 study of 12 male patients with stable systolic heart failure, acetazolamide significantly reduced the number of central apnea episodes from an average of 49 to 23 per hour, indicating its efficacy in treating central sleep apnea.

Acetazolamide also improved overall sleep quality and reduced daytime fatigue and unintentional daytime sleepiness, suggesting it positively impacts both sleep and daily functioning in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Javaheri, S.[2022]

A new high-performance liquid chromatography (HPLC) method has been developed to accurately measure acetazolamide in both tablet and injection forms, ensuring reliable quantification for clinical use.

The method utilizes a specific extraction process and a commercially available C18 cartridge column, achieving quick retention times of approximately 2.50 minutes for acetazolamide, which enhances the efficiency of drug analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of acetazolamide in dosage forms by high performance liquid chromatography. Gomaa, ZS.[2013]

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]

A highly sensitive method for analyzing acetazolamide in plasma was developed, capable of detecting levels as low as 25 ng/ml, which is crucial for monitoring drug levels in patients.

The method allows for the study of plasma level profiles of various dosage forms of acetazolamide, enhancing our understanding of its pharmacokinetics and potential therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assay for acetazolamide in plasma. Bayne, WF., Rogers, G., Crisologo, N.[2019]

A new method using stable-isotope dilution GC-MS has been developed to accurately measure acetazolamide levels in human urine, demonstrating high precision and reliability for pharmacological studies.

The method successfully quantified urinary excretion of acetazolamide after ingestion, indicating its potential for monitoring drug levels and effectiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GC-NICI-MS analysis of acetazolamide and other sulfonamide (R-SO2-NH2) drugs as pentafluorobenzyl derivatives [R-SO2-N(PFB)2] and quantification of pharmacological acetazolamide in human urine. Begou, O., Drabert, K., Theodoridis, G., et al.[2022]

The new diazepam rectal gel (Diastat) showed rapid absorption, reaching peak plasma levels within 70 minutes and demonstrating a high bioavailability of 90.4%, making it an effective alternative to intravenous administration.

Cognitive effects were mild and temporary, with subjects experiencing slight impairments in alertness and performance on neuropsychological tests, but these effects resolved within 4 hours, indicating that Diastat is a safe option for administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-blind, crossover comparison of the pharmacokinetics and cognitive effects of a new diazepam rectal gel with intravenous diazepam. Cloyd, JC., Lalonde, RL., Beniak, TE., et al.[2019]

Citations

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An open-label study of oral acetazolamide for the prevention ... DISCUSSION. In patients with schizophrenia or psychosis, several factors contribute to weight gain. The main contributors are a sedentary ...

2. withpower.com withpower.com/trial/phase-2-psychotic-disorders-9-2021-cbdfb

Acetazolamide for Schizophrenia (APTS Trial) This trial is for adults aged 18-55 with treatment-resistant schizophrenia, having a PANSS score over 60 and significant positive symptoms despite medication.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04887792

Acetazolamide for Treatment Resistant Schizophrenia Study Overview. Brief Summary. This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide. Detailed Description.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/6442984/

Antipsychotic and prophylactic effects of acetazolamide ... The high therapeutic effects were particularly observed in Types I, II and III. It was less effective against atypical schizophrenia. Acetazolamide showed the ...

5. ctv.veeva.com ctv.veeva.com/study/acetazolamide-for-treatment-resistant-schizophrenia

Acetazolamide for Treatment Resistant Schizophrenia (APTS) This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9856781/

Acetazolamide for Bipolar Disorders: A Scoping Review Of the 50 treated patients, almost two thirds were experiencing psychosis or mania, and one third had depression. Most of the latter patients ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/j.1440-1819.1984.tb00791.x

Antipsychotic and Prophylactic Effects of Acetazolamide ... References. · 1 Coppen, A. · 2 Endo, M., Takahashi, S. · 3 Fukuda, T.: Atypical psychosis. · 4 Fukuma, E. · 5 Hatotani, N.: Endocrinological studies on schizophrenia ...