Acetazolamide for Schizophrenia
(APTS Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen ByVishwajit L Nimgaonkar, M.D., Ph.D.
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Vishwajit Nimgaonkar, MD PhD
Must be taking: Antipsychotics
Disqualifiers: Substance abuse, Epilepsy, Pregnancy, others
Stay on your current meds
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.
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.
What data supports the effectiveness of the drug acetazolamide for schizophrenia?
Research shows that acetazolamide can increase blood flow in certain areas of the brain, which might help with conditions involving brain function. However, there is no direct evidence from the provided studies that it is effective for treating schizophrenia.
12345Is acetazolamide generally safe for humans?
Acetazolamide is generally safe for humans, but it can cause serious allergic reactions in people with sulfonamide allergies, leading to potentially life-threatening conditions like anaphylactic shock (a severe allergic reaction). It's important to inform your doctor about any sulfonamide allergies before taking acetazolamide.
678910How does the drug acetazolamide differ from other treatments for schizophrenia?
Acetazolamide is unique because it is primarily known as a diuretic and a respiratory stimulant, often used for conditions like high altitude sickness and sleep apnea, rather than for schizophrenia. Its use in schizophrenia is novel and may involve different mechanisms compared to standard antipsychotic medications.
1112131415Eligibility Criteria
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).
+2 more
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.
+3 more
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Active Control
Group I: AcetazolamideActive Control1 Intervention
acetazolamide capsules
Group II: PlaceboActive Control1 Intervention
Identical gelatin capsules
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PittsburghPittsburgh, PA
Loading ...
Who Is Running the Clinical Trial?
Vishwajit Nimgaonkar, MD PhDLead Sponsor
Stanley Medical Research InstituteCollaborator
References
Acetazolamide effect on vascular response in areas with diaschisis as measured by Tc-99m HMPAO brain SPECT. [2019]The effects of acetazolamide (Diamox) on vascular response were investigated in areas with intrahemispheric thalamic diaschisis and crossed cerebellar diaschisis using consecutive Tc-99m HMPAO brain SPECT studies before and after Diamox administration. All six patients with thalamic diaschisis and five of eight patients with crossed cerebellar diaschisis at baseline showed significantly augmented perfusion after Diamox administration in the affected thalamus and cerebellum compared with that in the contralateral unaffected areas. These results suggest more dilatation of the arterioles in areas with diaschisis after Diamox administration than in areas without diaschisis. Diamox may produce relative luxury perfusion in areas with diaschisis.
A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP). [2019]Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for 123I(IMP), which could have diagnostic implications.
A single-blind, crossover comparison of the pharmacokinetics and cognitive effects of a new diazepam rectal gel with intravenous diazepam. [2019]The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat) with intravenously administered DZP.
[133Xe-DSPECT: normal values of resting cerebral blood flow and reserve capacity]. [2015]Using the 133Xe-DSPECT technique, quantitative measurements of regional cerebral blood flow (rCBF) were performed before and after provocation with acetazolamide (Diamox) i.v. in 32 patients without evidence of brain disease (normals). In 6 cases, additional studies were carried out to establish the time of maximal rCBF increase which was found to be approximately 15 min p.i. 1 g of Diamox increases the rCBF from 58 +/- 8 at rest to 73 +/- 5 ml/100 g/min. A Diamox dose of 2 g (9 cases) causes no further rCBF increase. After plotting the rCBF before provocation (rCBFR) and the Diamox-induced rCBF increase (reserve capacity, delta rCBF) the regression line was delta rCBF = -0,6XrCBFR + 50 (correlation coefficient: r = -0,77). In normals with relatively low rCBF values at rest, Diamox increases the reserve capacity much more than in normals with high rCBF values before provocation. It can be expected that this concept of measuring rCBF at rest and the reserve capacity will increase the sensitivity of distinguishing patients with reversible cerebrovascular disease (even bilateral) from normals.
Dixyrazine premedication for cataract surgery. A comparison with diazepam. [2019]Peroral dixyrazine (15-30 mg, n = 50) and diazepam (4-10 mg, n = 50) were used as premedicants for geriatric patients having cataract surgery under regional block. Compared to the diazepam patients, a larger number of the dixyrazine medicated patients appeared anxious, and there was a statistically significant difference between the groups, when summing up changes in anxiety throughout the study period. The dixyrazine patients needed more frequent supplementation with intravenous sedative drugs, compared with their diazepam counterparts. Peroral dixyrazine is an applicable choice for calm patients, when only slight sedation, or avoidance of somnolence are required.
Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma. [2019]Our purpose was to compare, in a crossover design,the hypotensive effect of oral acetazolamide (Diamox) and topical dorzolamide (Trusopt) in patients with pediatric glaucoma.
Effect of acetazolamide (Diamox) on tear secretion. [2019]The side effects of acetazolamide (Diamox) on lacrimation were measured in rats by means of the cotton-thread tear test. After a daily oral 1-mg dose (administered for five days), comparable to the dose used for adult humans on a drug-to-bodyweight basis, tear production remained unaffected but the lacrimal peroxidase secretion decreased by 60% of the baseline level. After withdrawal of acetazolamide the peroxidase secretion returned to the baseline level.
Short-term dose response characteristics of acetazolamide in man. [2019]Nine patients with ocular hypertension each randomly received on separate days 0, 63, 125, 250, and 500 mg of acetazolamide (Diamox). In a double masked manner, acetazolamide plasma levels and intraocular pressure were monitored for seven hours following administration. Plasma levels increased linearly with dose, reaching 30 microgram/ml with the 500-mg dose. Maximum plasma levels occurred at one hour, and the minimum IOP was at two hours. The maximum IOP effect was a 30% to 35% fall. The IOP response was related to dose and plasma level, up to a 63-mg dose, which produced an average fall of 8.2 mm Hg. Little further average effect was documented at higher doses or plasma levels. The duration of response was slightly prolonged by 250 mg, but 500 mg showed no greater response. Thus, a 63-mg dose or a plasma level of 4 to 5 microgram/ml was as effective in lowering IOP as higher doses that produced plasma levels of 10 microgram/ml or more.
Effectiveness of generic acetazolamide. [2019]Comparisons were made between the ocular hypotensive effects and blood levels achieved with the single-dose administration of either generic acetazolamide or brand-name acetazolamide (Diamox). The relative cost of the two products was surveyed. The effect of food on the absorption of acetazolamide was also evaluated. The generic and brand-name acetazolamide were equivalent in their effects on intraocular pressure. Comparable blood levels of acetazolamide were obtained with the two products. The cost of generic acetazolamide was 37% less than brand-name acetazolamide, when available. Food intake did not appear to influence the absorption of acetazolamide.
[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. [2017]A woman aged 66 was prescribed acetazolamide (Diamox) in the outpatient clinic because of glaucoma. She went into irreversible anaphylactic shock with massive pulmonary oedema, probably due to a cross reaction in sulphonamide allergy. Before prescribing acetazolamide, the physician should inquire about sulphonamide allergy because of the related chemical structure of the substances. Such an allergy should be regarded as a contraindication.
Assay for acetazolamide in plasma. [2019]A method for the analysis of acetazolamide, 5-acetamido-1,3,4-thiadiazole-2-sulfonamide, sensitive to 25 ng/ml in plasma, was developed. After extraction of acetazolamide and its propionyl analog, 5-propionamido-1,3,4-thiadiazole-2-sulfonamide, the internal standard, from plasma with ethyl acetate and removal of lipids from the residue of the ethyl acetate extract with methylene chloride, the sulfonamides were chromatographed on an octadecyl trichlorosilane bonded phase using high-pressure liquid chromatography. The method was developed to study plasma level profiles of different dosage forms of acetazolamide.
Acetazolamide and high altitude diseases. [2013]Acetazolamide is a useful prophylactic for acute mountain sickness causing marked reduction in headache, nausea, vomiting, weakness, etc. Improvements correlate with increased arterial oxygen concentrations, reduction in proteinuria and peripheral oedema and other objective measures of acute mountain sickness. Evidence that Acetazolamide is beneficial for pulmonary oedema or cerebral oedema is scanty because of the lower frequency of these severe forms of mountain sickness. Dexamethasone, used prophylactically, also reduces the symptoms of acute mountain sickness partly due to its euphoric effect. Use of Acetazolamide as a treatment for established acute mountain sickness has been investigated. Large doses of Acetazolamide increase arterial oxygen levels over a few hours and this leads to a reduction of symptoms but data is limited and faster acting carbonic anhydrides inhibitors such as Methazolamide may be preferable in an emergency situation. There is no comparison of the effectiveness of Acetazolamide with other drugs used for treating acute mountain sickness such as steroids and calcium channel blocking drugs. Also, there is no data on drug combinations which could have additive effects and thereby be more beneficial than individual drugs.
Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. [2022]Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude.
Determination of acetazolamide in dosage forms by high performance liquid chromatography. [2013]A high performance liquid chromatographic assay for the quantitation of acetazolamide in both tablet and injection form is described. Acetazolamide is extracted with 0.005 M NaOH solution containing 0.3 mg/mL sulphadiazine (internal standard). A commercially available mu-Bondapak C18 cartridge column was used for the separation together with a mobile phase made of acetonitrile, methanol and sodium acetate buffer mixture (10:2:88) (pH 4) at a flow-rate of 4 mL/min. Retention times of about 2.50 and 3.36 min were obtained for the drug and the internal standard, respectively.
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. [2022]Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO2-NH2) and is one of the strongest pharmacological inhibitors of carbonic anhydrase activity. Acetazolamide is excreted unchanged in the urine. Here, we report on the development, validation and biomedical application of a stable-isotope dilution GC-MS method for the reliable quantitative determination of acetazolamide in human urine. The method is based on evaporation to dryness of 50 μL urine aliquots, base-catalyzed derivatization of acetazolamide (d0-AZM) and its internal standard [acetylo-2H3]acetazolamide (d3-AZM) in 30 vol% pentafluorobenzyl (PFB) bromide in acetonitrile (60 min, 30 °C), reconstitution in toluene (200 μL) and injection of 1-μL aliquots. The negative-ion chemical ionization (NICI) mass spectra (methane) of the PFB derivatives contained several intense ions including [M]‒ at m/z 581 for d0-AZM and m/z 584 for d3-AZM, suggesting derivatization of their sulfonamide groups to form N,N-dipentafluorobenzyl derivatives (R-SO2-N(PFB)2), i.e., d0-AZM-(PFB)2 and d3-AZM-(PFB)2, respectively. Quantification was performed by selected-ion monitoring of m/z 581 and 83 for d0-AZM-(PFB)2 and m/z 584 and 86 for d3-AZM-(PFB)2. The limits of detection and quantitation of the method were determined to be 300 fmol (67 pg) and 1 μM of acetazolamide, respectively. Intra- and inter-assay precision and accuracy for acetazolamide in human urine samples in pharmacologically relevant concentration ranges were determined to be 0.3%-4.2% and 95.3%-109%, respectively. The method was applied to measure urinary acetazolamide excretion after ingestion of a 250 mg acetazolamide-containing tablet (Acemit®) by a healthy volunteer. Among other tested sulfonamide drugs, methazolamide (MM, 236) was also found to form a N,N-dipentafluorobenzyl derivative, whereas dorzolamide (MM, 324) was hardly detectable. No GC-MS peaks were obtained from the PFB bromide derivatization of hydrochlorothiazide (MM, 298), xipamide (MM, 355), indapamide and metholazone (MM, 366 each) or brinzolamide (MM, 384). We demonstrate for the first time that sulfonamide drugs can be derivatized with PFB bromide and quantitated by GC-MS. Sulfonamides with MM larger than 236 are likely to be derivatized by PFB bromide but to lack thermal stability.