Acetazolamide for Treatment Resistant Schizophrenia

NCT ID: NCT04887792

Last Updated: 2025-04-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-01

Study Completion Date

2026-12-30

Brief Summary

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This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.

Detailed Description

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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

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Schizophrenia Schizo Affective Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

This study will be a randomized placebo-controlled sequential parallel comparison design (SPCD).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participant, care providers, Investigators and assessors will all be blinded. Study staff responsible for randomization will be unblinded.

Study Groups

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Acetazolamide

acetazolamide capsules

Group Type ACTIVE_COMPARATOR

Acetazolamide

Intervention Type DRUG

ACZ 250 mg/day in gelatin capsules will be administered initially and increased over 7-10 days to 2g/day.

Placebo

Identical gelatin capsules

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Identical gelatin capsules will be prepared by filling with inert excipients.

Interventions

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Acetazolamide

ACZ 250 mg/day in gelatin capsules will be administered initially and increased over 7-10 days to 2g/day.

Intervention Type DRUG

Placebo

Identical gelatin capsules will be prepared by filling with inert excipients.

Intervention Type DRUG

Other Intervention Names

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Diamox

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanley Medical Research Institute

OTHER

Sponsor Role collaborator

Vishwajit Nimgaonkar, MD PhD

OTHER

Sponsor Role lead

Responsible Party

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Vishwajit Nimgaonkar, MD PhD

Professor of Psychiatry and Human Genetics

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

St John's Medical College Hospital

Bangalore, , India

Site Status RECRUITING

Countries

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United States India

Central Contacts

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

Role: CONTACT

412-246-6356

Maribeth A Wesesky, BPS

Role: CONTACT

4122957017

Facility Contacts

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Maribeth A Wesesky, BPS

Role: primary

412-295-7017

Smita N Deshpande, M.D.

Role: primary

(91)- 93126-54702

Triptish Bhatia, Ph.D.

Role: backup

(91)-11-23404363

Other Identifiers

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STUDY20010237

Identifier Type: -

Identifier Source: org_study_id

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