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AzTrials

SchizophreniaPhase 4NCT06236451

Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

A Phase 4 study testing Aripiprazole and Risperidone in people with Schizophrenia, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Schizophrenia is a serious mental disorder with a global prevalence of 1%. The main cause of this condition is dysfunction in the signaling of neurotransmitters dopamine, serotonin, glutamate and Gamma-aminobutyric acid .According to recent research, a disturbed cellular energy state caused by mitochondrial… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Schizophrenia
What is being tested?
Aripiprazole and Risperidone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteIndia
Study dates
5 Apr 2024to 12 Nov 2025
Phase
Phase 4
Are there results?
None posted in the registry

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 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients meeting the DSM-5 criteria for diagnosis of schizophrenia.
  • Treatment naıv̈ e patients or patients who had not taken any antipsychotic drugs for at least 4 weeks before recruitment.
  • Patients of either sex between the ages of 18 and 60 years.
  • Legally authorized representative (LAR) of patients consenting to participate in the study by signing the informed consent form.

Who cannot join

  • Patients diagnosed with other psychiatric disorders including schizoaffective disorder or schizophrenia with somatoform disorders.
  • Highly agitated patients who need immediate indoor-based treatment.
  • Patients with known mitochondrial disorders (MELAS, LHON, Leigh syndrome, KearnsSayre syndrome, MERRF etc.)
  • Patients with history of comorbidities like cardiovascular, renal, hepatic, neurological, respiratory or endocrinal diseases or malignancies.
  • Patients with history of substance abuse.
  • Pregnant or lactating mothers.

Trial locations and contacts

1 site in 1 country.

India1 site
  • All India Institute of Medical Sciences (AIIMS)

    Bhubaneswar, Odisha, 751019

Other trials in India

About this study

Official title: A Randomized Controlled Trial to Evaluate Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

Schizophrenia is a serious mental disorder with a global prevalence of 1%. The main cause of this condition is dysfunction in the signaling of neurotransmitters dopamine, serotonin, glutamate and Gamma-aminobutyric acid .According to recent research, a disturbed cellular energy state caused by mitochondrial dysfunction is thought to be a factor in the development of schizophrenia.

The aim of the treatment of schizophrenia is to reduce symptoms and is mainly based on the monoamine hypothesis. Atypical antipsychotics are the first-line of treatment.

Read more

Certain typical and atypical antipsychotic medications have been shown in prior preclinical research to decrease mitochondrial respiratory chain complex I activity. In contrast to individuals who were drug-naive, Casademont et al. found a significant decrease in complex I activity with haloperidol and risperidone in one cross-sectional observational study. Also, there is evidence suggesting that mitochondrial dysfunction is linked to the extrapyramidal side effects seen with antipsychotics.

To date, there are no randomized controlled trials that assess the effect of these drugs on mitochondrial functions. Hence, the present randomized controlled trial has been planned to evaluate and compare the clinical and biochemical markers of mitochondrial dysfunction in schizophrenia patients treated with the atypical antipsychotics risperidone and aripiprazole.

Conditions
Schizophrenia
Keywords
Schizophrenia, Mitochondrial electron transport chain complex, Aripiprazole, Risperidone, Mitochondrial dysfunction
Medical subject headings
Schizophrenia, Mitochondrial Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AripiprazoleDrug

    Aripiprazole will be started at dose of 10 mg/day and increased to a stable dose of 20 mg/day over 2-3 weeks and will be continued till 12 weeks.

  • RisperidoneDrug

    Risperidone will be started at dose of 2 mg/day and increased to a stable dose of 6 mg/day over 2-3 weeks and continued till 12 weeks.

Study groups in NCT06236451
Study groupRoleWhat they receive
Aripiprazole groupExperimentalAripiprazole will be started at dose of 10 mg/day and increased to a stable dose of 20 mg/day over 2-3 weeks and will be continued till 12 weeks.
Receives: Drug: Aripiprazole
Risperidone groupActive comparatorRisperidone will be started at dose of 2 mg/day and increased to a stable dose of 6 mg/day over 2-3 weeks and continued till 12 weeks.
Receives: Drug: Risperidone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Mitochondrial respiratory chain complex I activity/concentration

    Mitochondrial respiratory chain complex I activity/concentration will be measured in platelets using a commercially available ELISA (enzyme-linked immunosorbent assay) kit at baseline and at 12 weeks of follow-up.

    Measured: 12 weeks

Secondary outcomes (8)
  1. Change in Serum lactate

    Serum lactate will be measured using spectrophotometry at baseline and at 12 weeks follow up

    Measured: 12 weeks

  2. Change in Serum creatine kinase

    Serum creatine kinase will be measured using autoanalyzer at baseline and at 12 weeks

    Measured: 12 weeks

  3. Change in Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores

    Newcastle Mitochondrial Disease Adult Scale (NMDAS) scoring of all patients will be assessed at baseline and at 12 weeks of follow-up. The NMDAS offers a range of 0 to 5 points for each question. The results from each of the first three sections' questions are added together to determine each section's score. The more severe the ailment, the higher the score.

    Measured: 12 weeks

  4. Change in Positive and Negative Syndrome Scale (PANSS) scores

    Positive and Negative Syndrome Scale (PANSS) scoring will be done at baseline and at 12 weeks follow-up. Out of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale. The scores for these scales are arrived at by summation of ratings across component items. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. The more severe the ailment, the higher the score.

    Measured: 12 weeks

  5. Responder rate

    A patient with a reduction of Positive and Negative Syndrome Scale (PANSS) scores by ≥50% from baseline will be considered a 'responder'..

    Measured: 12 weeks

  6. Change in Serum pyruvate

    Serum pyruvate will be measured using spectrophotometry at baseline and at 12 weeks follow up.

    Measured: 12 weeks

  7. Incidence of treatment-emergent adverse events

    Incidence of treatment-emergent adverse events in both study groups reported throughout the study duration will be reported.

    Measured: 12 weeks

  8. Severity of extrapyramidal adverse effects

    Total score severity of extrapyramidal adverse effects will be assessed by Modified Simpson-Angus Scale. It is a 10-item scale where each item is rated on a 0-4 scale, with higher scores indicating greater severity. The total score is used to gauge the presence and degree of movement disorders, ranging from normal (score<3) to severe (score>12).

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2024
  2. Study start5 Apr 2024
  3. Primary completion3 Nov 2025
  4. Study completion12 Nov 2025

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06236451
Sponsor's protocol ID
PGThesis/2023-24/100
Status last verified
Nov 2025
First submitted
24 Jan 2024
Last updated
25 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) underlying the results of this study will be shared with qualified researchers upon reasonable request. Data will be available after publication and subject to review of a data access proposal and data use agreement.

Publications

  • Hardy RE, Chung I, Yu Y, Loh SHY, Morone N, Soleilhavoup C, Travaglio M, Serreli R, Panman L, Cain K, Hirst J, Martins LM, MacFarlane M, Pryde KR. The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors. Biol Direct. 2023 Aug 1;18(1):43. doi: 10.1186/s13062-023-00375-9.

    PubMed 37528429
  • Luptak M, Fisar Z, Hroudova J. Effect of Novel Antipsychotics on Energy Metabolism - In Vitro Study in Pig Brain Mitochondria. Mol Neurobiol. 2021 Nov;58(11):5548-5563. doi: 10.1007/s12035-021-02498-4. Epub 2021 Aug 8.

    PubMed 34365585
  • Modica-Napolitano JS, Lagace CJ, Brennan WA, Aprille JR. Differential effects of typical and atypical neuroleptics on mitochondrial function in vitro. Arch Pharm Res. 2003 Nov;26(11):951-9. doi: 10.1007/BF02980205.

    PubMed 14661862
  • Scaini G, Rochi N, Morais MO, Maggi DD, De-Nes BT, Quevedo J, Streck EL. In vitro effect of antipsychotics on brain energy metabolism parameters in the brain of rats. Acta Neuropsychiatr. 2013 Feb;25(1):18-26. doi: 10.1111/j.1601-5215.2012.00650.x.

    PubMed 26953070
  • Casademont J, Garrabou G, Miro O, Lopez S, Pons A, Bernardo M, Cardellach F. Neuroleptic treatment effect on mitochondrial electron transport chain: peripheral blood mononuclear cells analysis in psychotic patients. J Clin Psychopharmacol. 2007 Jun;27(3):284-8. doi: 10.1097/JCP.0b013e318054753e.

    PubMed 17502776
  • Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M. Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci Biobehav Rev. 2015 Jan;48:10-21. doi: 10.1016/j.neubiorev.2014.11.005. Epub 2014 Nov 15.

    PubMed 25446950
  • Fizikova I, Dragasek J, Racay P. Mitochondrial Dysfunction, Altered Mitochondrial Oxygen, and Energy Metabolism Associated with the Pathogenesis of Schizophrenia. Int J Mol Sci. 2023 Apr 28;24(9):7991. doi: 10.3390/ijms24097991.

    PubMed 37175697
  • Schaefer AM, Phoenix C, Elson JL, McFarland R, Chinnery PF, Turnbull DM. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology. 2006 Jun 27;66(12):1932-4. doi: 10.1212/01.wnl.0000219759.72195.41.

    PubMed 16801664
  • Leucht S, Davis JM, Engel RR, Kane JM, Wagenpfeil S. Defining 'response' in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology. 2007 Sep;32(9):1903-10. doi: 10.1038/sj.npp.1301325. Epub 2007 Feb 7.

    PubMed 17287825
  • Venegas V, Halberg MC. Measurement of mitochondrial DNA copy number. Methods Mol Biol. 2012;837:327-35. doi: 10.1007/978-1-61779-504-6_22.

    PubMed 22215558
  • Shaju A, Mishra BR, Mohapatra D, Mishra A, Srinivasan A, Maiti R. Mitochondrial dysfunction in schizophrenia and its modulation by atypical antipsychotic drugs: A randomized controlled trial. J Psychopharmacol. 2026 Jun 26:2698811261453937. doi: 10.1177/02698811261453937. Online ahead of print.

    PubMed 42362495
  • Shaju A, Mohapatra D, Mishra BR, Mishra A, Srinivasan A, Maiti R. Evaluation of atypical antipsychotic-induced mitochondrial dysfunction in patients with schizophrenia: a randomised controlled trial protocol. BMJ Open. 2025 Oct 15;15(10):e098173. doi: 10.1136/bmjopen-2024-098173.

    PubMed 41093357

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aripiprazole and Risperidone in people with Schizophrenia, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.

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 4 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: finished, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in 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 phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Mitochondrial respiratory chain complex I activity/concentration (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06236451, which also lists 12 linked publications.

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 25 Nov 2025.

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