SchizophreniaPhase 1/2APTSNCT04887792
Acetazolamide for Treatment Resistant Schizophrenia
A Phase 1/2 study testing Acetazolamide in people with Schizophrenia and Schizo Affective Disorder, run by Vishwajit Nimgaonkar, MD PhD at 2 sites in 2 countries.
Trial summary
This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizo Affective Disorder
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Feb 2022to 30 Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Written informed consent.
- Both genders, ages 18-55 years (older patients may not tolerate high ACZ dose).
- PANSS total score > 60 and Score > 4 on one or more items of the 'positive' syndrome items (P1-P7), following treatment at therapeutic doses for 6 weeks with different APDs on 2 occasions.
- Stable dose of antipsychotic drug (APD) for > 1 month, continued throughout the study.
- Not participating in another randomized controlled clinical trial (RCT).
Who cannot join
- Substance abuse in the past month/dependence past 6 months with the exception of methadone prescribed for opiate withdrawal.
- History or current medical/neurological illnesses that may lead to unstable course, e.g., epilepsy.
- Pregnancy.
- Acetazolamide (ACZ) contraindications: hypersensitivity to ACZ; history of renal hyperchloremic acidosis; Addison's disease/adrenal failure; chronic closed angle-closure glaucoma.
- Current or prior treatment with ACZ or history of hypersensitivity to ACZ.
- Intellectual disability as defined in DSM 5.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Maribeth A Wesesky, BPS, 412-295-7017, weseskyma@upmc.edu
Satish Iyengar, Ph.D.
India1 site, 1 recruiting
- Recruiting
St John's Medical College Hospital
Bangalore
Smita N Deshpande, M.D., (91)- 93126-54702, smitadeshp@gmail.com
Triptish Bhatia, Ph.D., (91)-11-23404363, bhatiatriptish@yahoo.co.in
About this study
Official title: A Randomized Controlled Trial of Acetazolamide for Patients With Treatment Resistant Schizophrenia
This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.
Read the detailed description
Schizophrenia (SZ) afflicts over 21 million people worldwide. Persons with SZ have a 10% suicide rate and their lifespan is curtailed by over 25 years. There is an urgent need for efficacious antipsychotic drugs (APDs), particularly, second line drugs, because only 30-40% of APD-treated patients attain remission and 30% of patients show little or no response. Currently, Clozapine is the only reliable second line APD, but it can cause serious blood dyscrasias. To fill the void, the investigators have conducted systematic reviews of prior data and in silico searches. In a prior double-blind crossover randomized placebo-controlled trial (RCT), adjunctive Acetazolamide (ACZ) caused ~20% improvement in positive and negative symptom scores when added to APDs among partially-responsive patients with SZ (ACZ 2G/day). No patients dropped out. The RCT is supported by several other open trials. ACZ also reduces weight, thus it could combat weight gain, a common APD side effect. Independently, our systematic in silico strategy based on protein networks and gene expression profiles also identified Acetazolamide (ACZ) as a repurposable drug for SZ.
ACZ crosses the blood-brain barrier. It is used to treat CNS diseases such as refractory seizures and idiopathic intracranial hypertension. Used for over 50 years, its side effects (SE) and adverse effects (AE) are well known and are manageable. It is a potent, specific inhibitor of carbonic anhydrase (CA), which catalyzes the conversion of CO2 to HCO3- and H+. CA is localized to pre-synaptic terminals and glial cells. It modulates GABAergic excitation, long-term synaptic transformation, attentional gating of memory storage and cerebrospinal fluid formation. Post-mortem brain and serological studies show raised CA levels in patients with psychotic/mood disorders. Several APDs also inhibit CA. The investigators thus postulate brain CA inhibition as the therapeutic target for ACZ in SZ.
The investigators propose a double-blind, crossover RCT for SZ using adjunctive ACZ. To maximize the risk/benefit ratio, the investigators will enroll inpatients and outpatients with treatment resistant SZ (trSZ) who meet defined criteria (N=60 RCT completers). ACZ or placebo will be added to prescribed APDs for 8 weeks utilizing the Sequential Parallel Comparison Design to maximize power. The investigators have extensive experience with RCTs. The investigators will ensure timely recruitment by approaching a large group of patients we serve, across 2 sites. If ACZ is beneficial, in future studies the investigators will pursue its implementation for trSZ, and seek variables associated with treatment response.
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Being tested
- Acetazolamide, Placebo
- Keywords
- Schizophrenia, Schizo Affective Disorder, acetazolamide
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Diamox
ACZ 250 mg/day in gelatin capsules will be administered initially and increased over 7-10 days to 2g/day.
PlaceboDrug
Identical gelatin capsules will be prepared by filling with inert excipients.
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Active comparator | acetazolamide capsules Receives: Drug: Acetazolamide |
| Placebo | Active comparator | Identical gelatin capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in positive symptoms
Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 7 Items, (minimum score = 7, maximum score = 49)
Measured: 24 weeks
Secondary outcomes (9)
Clinical Severity
Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 30 Items, (minimum score = 7, maximum score = 210)
Measured: 24 weeks
Clinical Severity
Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 7 Items, (minimum score = 7, maximum score = 49)
Measured: 24 weeks
Cognition
Trail Making Test (TMT) 86: This test estimates attention, working memory and executive function.
Measured: 24 weeks
Clinical Severity
"Clinical Global Impression - Severity" (CGI-S). The CGI-S is a 7-point scale that rates the severity of the patient's illness at the time of assessment. The minimum score is 1 and the maximum score is 100. Scores which are lower in value indicate greater severity of illness. Higher scores indicate less severe illness.
Measured: 24 weeks
Social Function
"Sheehan's Disability Scale" (SDS). The SDS is a self-report is a self-report tool that assesses functional impairment in work/school, social and family life with a 10-point visual analogue scale. The minimum score is 0 and the maximum score is 10. Scores which are lower in value indicate better outcomes with less disability. Higher scores indicate more severe illness with greater disability.
Measured: 24 weeks
Global Assessment of Function
"Global Assessment of Function" (GAF). The GAF is an assessor reporting tool that assesses level of functioning on a 1 to 100 point scale. The minimum score is 1 and the maximum score is 100. Scores which are higher in value indicate better outcomes with less disability. Lower scores indicate more severe illness with greater disability.
Measured: 24 weeks
Measure of satisfaction with one's Quality of Life (Quality of Life Scale/QOLS)
The QOLS was originally a 15-item instrument that measured five conceptual domains of quality of life: material and physical well-being, relationships with other people, social, community and civic activities, personal development and fulfillment, and recreation. After descriptive research that queried persons with chronic illness on their perceptions of quality of life, the instrument was expanded to include one more item: Independence, the ability to do for yourself. Thus, the QOLS in its present format contains 16 items.
The QOLS is scored by adding up the score on each item to yield a total score for the instrument. Scores can range from 16 to 112. The QOLS scores are summed so that a higher score indicates higher quality of life. Average total score for healthy populations is about 90.
Measured: 24 weeks
Socio-Economic Status
We will use a composite measure of educational attainment and pretax family (household) income based on the Hollingshead Redlich 4-factor index.
The Hollingshead Four Factor Index of Socioeconomic Status is a survey designed to measure social status of an individual based on four domains: marital status, retired/employed status, educational attainment, and occupational prestige. The participant's education code is obtained education code is rated on a 7-point scale that lists highest grade completed. The participant's occupational code is rated on a 9-point scale.
SES=0.5X education score+0.3Xincome score+ 0.3X occupation score.
Measured: 24 weeks
Side Effects
We will make a list of side effects for CGY noted in the Drug Formulary. This list will be a comprehensive listing of possible side effects by body system, grading both the frequency and severity of the symptoms.
Frequency (days per week): Severity:
0 = Absent
- = 1-2 days 1 = mild, does not interfere with functioning
- = 3-4 days 2 = moderate, some interference with functioning
- = 5-7 days 3 = severe, functioning is significantly impaired
Frequency scores can range from 0 to 3, with higher scores equaling higher frequency.
Severity scores can range from 1 to 3, with higher scores equaling greater severity.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study start1 Feb 2022
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This study will be a randomized placebo-controlled sequential parallel comparison design (SPCD).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vishwajit Nimgaonkar, MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Sponsor-investigator, Vishwajit Nimgaonkar, MD PhD, University of Pittsburgh
- Investigators
- Vishwajit L Nimgaonkar, M.D., Ph.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04887792
- Sponsor's protocol ID
- STUDY20010237
- Acronym
- APTS
- Status last verified
- Jul 2026
- First submitted
- 15 Dec 2020
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No individual data will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Acetazolamide for Patients With Treatment Resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT04887792
- Acronym / sponsor ID
- APTS / STUDY20010237
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Keywords
- Schizophrenia, Schizo Affective Disorder, acetazolamide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Vishwajit Nimgaonkar, MD PhDUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.
Detailed description
Schizophrenia (SZ) afflicts over 21 million people worldwide. Persons with SZ have a 10% suicide rate and their lifespan is curtailed by over 25 years. There is an urgent need for efficacious antipsychotic drugs (APDs), particularly, second line drugs, because only 30-40% of APD-treated patients attain remission and 30% of patients show little or no response. Currently, Clozapine is the only reliable second line APD, but it can cause serious blood dyscrasias. To fill the void, the investigators have conducted systematic reviews of prior data and in silico searches. In a prior double-blind crossover randomized placebo-controlled trial (RCT), adjunctive Acetazolamide (ACZ) caused ~20% improvement in positive and negative symptom scores when added to APDs among partially-responsive patients with SZ (ACZ 2G/day). No patients dropped out. The RCT is supported by several other open trials. ACZ also reduces weight, thus it could combat weight gain, a common APD side effect. Independently, our systematic in silico strategy based on protein networks and gene expression profiles also identified Acetazolamide (ACZ) as a repurposable drug for SZ.
ACZ crosses the blood-brain barrier. It is used to treat CNS diseases such as refractory seizures and idiopathic intracranial hypertension. Used for over 50 years, its side effects (SE) and adverse effects (AE) are well known and are manageable. It is a potent, specific inhibitor of carbonic anhydrase (CA), which catalyzes the conversion of CO2 to HCO3- and H+. CA is localized to pre-synaptic terminals and glial cells. It modulates GABAergic excitation, long-term synaptic transformation, attentional gating of memory storage and cerebrospinal fluid formation. Post-mortem brain and serological studies show raised CA levels in patients with psychotic/mood disorders. Several APDs also inhibit CA. The investigators thus postulate brain CA inhibition as the therapeutic target for ACZ in SZ.
The investigators propose a double-blind, crossover RCT for SZ using adjunctive ACZ. To maximize the risk/benefit ratio, the investigators will enroll inpatients and outpatients with treatment resistant SZ (trSZ) who meet defined criteria (N=60 RCT completers). ACZ or placebo will be added to prescribed APDs for 8 weeks utilizing the Sequential Parallel Comparison Design to maximize power. The investigators have extensive experience with RCTs. The investigators will ensure timely recruitment by approaching a large group of patients we serve, across 2 sites. If ACZ is beneficial, in future studies the investigators will pursue its implementation for trSZ, and seek variables associated with treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will be a randomized placebo-controlled sequential parallel comparison design (SPCD).
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Active comparator | Drug: Acetazolamideacetazolamide capsules |
| Placebo | Active comparator | Drug: PlaceboIdentical gelatin capsules |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Written informed consent.
- Both genders, ages 18-55 years (older patients may not tolerate high ACZ dose).
- PANSS total score > 60 and Score > 4 on one or more items of the 'positive' syndrome items (P1-P7), following treatment at therapeutic doses for 6 weeks with different APDs on 2 occasions.
- Stable dose of antipsychotic drug (APD) for > 1 month, continued throughout the study.
- Not participating in another randomized controlled clinical trial (RCT).
Key exclusion criteria (6 listed)
- Substance abuse in the past month/dependence past 6 months with the exception of methadone prescribed for opiate withdrawal.
- History or current medical/neurological illnesses that may lead to unstable course, e.g., epilepsy.
- Pregnancy.
- Acetazolamide (ACZ) contraindications: hypersensitivity to ACZ; history of renal hyperchloremic acidosis; Addison's disease/adrenal failure; chronic closed angle-closure glaucoma.
- Current or prior treatment with ACZ or history of hypersensitivity to ACZ.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetazolamideAlso: DiamoxACZ 250 mg/day in gelatin capsules will be administered initially and increased over 7-10 days to 2g/day. | Drug | Acetazolamide |
| PlaceboIdentical gelatin capsules will be prepared by filling with inert excipients. | Drug | Placebo |
Primary outcome
Change in positive symptoms
Time frame: 24 weeks
Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 7 Items, (minimum score = 7, maximum score = 49)
9 secondary outcomes
Clinical Severity
Time frame: 24 weeks
Clinical Severity
Time frame: 24 weeks
Cognition
Time frame: 24 weeks
Clinical Severity
Time frame: 24 weeks
Social Function
Time frame: 24 weeks
Global Assessment of Function
Time frame: 24 weeks
Measure of satisfaction with one's Quality of Life (Quality of Life Scale/QOLS)
Time frame: 24 weeks
Socio-Economic Status
Time frame: 24 weeks
Side Effects
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Individual participant dataSharing planned: No. No individual data will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vishwajit L Nimgaonkar, M.D., Ph.D. principal investigator
University of Pittsburgh
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Acetazolamide in people with Schizophrenia and Schizo Affective Disorder, run by Vishwajit Nimgaonkar, MD PhD at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vishwajit L Nimgaonkar, M.D., Ph.D. (412-246-6356, vishwajitNL@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in positive symptoms (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.