Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

Treatment Resistant Schizophrenia Clinical Trial

Official title:

Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia: A Randomized, Group Sequential Adaptive Design, Controlled Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05944510
• Other study ID #: AIIMS BBSR/PGThesis/23-24/02
• Status: Recruiting
• Phase: Phase 4
• Start date: August 31, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: RITUPARNA MAITI, M.D.
• Phone: 9438884191
• Email: pharm_rituparna[@]aiimsbhubaneswar.edu.in
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Dextromethorphan acts as N-methyl-D-aspartate (NMDA) antagonist. In Treatment resistant schizophrenia(TRS) the efficacy of treatment response by clozapine is only around 40%. Numerous augmentation agent have been tried which includes antipsychotics, anticonvulsants, antidepressants and NMDA antagonist. The NMDA antagonist such as Riluzole and Memantine have shown good efficacy in TRS. Therefore we are evaluating NMDA antagonist, dextromethorphan in TRS. The dextromethorphan or placebo will be administered along with clozapine in TRS patients. The study is randomized double blind placebo controlled group sequential trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: December 31, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Schizophrenia patients who are diagnosed as treatment-resistant schizophrenia (TRS) defined as having been tried and not responded to any two antipsychotic medication for a duration of 6 weeks with dose equivalent of 600 mg of chlorpromazine and initiated on clozapine for the treatment of the same.

• The patients who are on stable dose of clozapine.

• Patients of either sex with age >18 years.

• Patients for whom legally authorized representative (LAR) are willing to give informed consent.

Exclusion Criteria:

• Patients with significant medical comorbidity.

• Patients with significant psychiatric comorbidity.

• Patients having active substance abuse history during the time of screening.

• Female patients who are pregnant or in reproductive age not using contraception.

• Female patients who are breast feeding

Related Conditions & MeSH terms

• Schizophrenia
• Treatment Resistant Schizophrenia

Intervention

Drug:
• Dextromethorphan
Dextromethorphan 30mg will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.
• Placebo
Matched placebo will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.

Locations

Country	Name	City	State
India	All India Institute of Medical Sciences (AIIMS)	Bhubaneswar	Odisha

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (5)

de Boer JN, Vingerhoets C, Hirdes M, McAlonan GM, Amelsvoort TV, Zinkstok JR. Efficacy and tolerability of riluzole in psychiatric disorders: A systematic review and preliminary meta-analysis. Psychiatry Res. 2019 Aug;278:294-302. doi: 10.1016/j.psychres.2019.06.020. Epub 2019 Jun 21. — View Citation

Kruse AO, Bustillo JR. Glutamatergic dysfunction in Schizophrenia. Transl Psychiatry. 2022 Dec 3;12(1):500. doi: 10.1038/s41398-022-02253-w. — View Citation

Siskind D, Siskind V, Kisely S. Clozapine Response Rates among People with Treatment-Resistant Schizophrenia: Data from a Systematic Review and Meta-Analysis. Can J Psychiatry. 2017 Nov;62(11):772-777. doi: 10.1177/0706743717718167. Epub 2017 Jun 28. — View Citation

Siu A, Drachtman R. Dextromethorphan: a review of N-methyl-d-aspartate receptor antagonist in the management of pain. CNS Drug Rev. 2007 Spring;13(1):96-106. doi: 10.1111/j.1527-3458.2007.00006.x. — View Citation

Vayisoglu S, Karahan S, Anil Yagcioglu AE. Augmentation of Antipsychotic Treatment with Memantine in Patients with Schizophrenia: A Systematic Review and Meta-Analysis. Turk Psikiyatri Derg. 2019 Winter;30(4):253-259. English, Turkish. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive and negative symptom scale score	The change in symptom scoring of schizophrenia at 12 weeks from baseline using Positive and negative symptom scale in the study groups. On this scale, total minimum score= 30, maximum score= 210. Higher score denotes a worse outcome.	Baseline and 12 weeks
Secondary	Responder rate	To analyze and compare responder rate between study groups. The responder rate is defined as = 25% reduction in PANSS score at 12 weeks from baseline.	12 weeks
Secondary	Incidence of clozapine resistance	To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy.	12 weeks
Secondary	Requirement of clozapine dose modification	To evaluate the proportion of patients requiring clozapine dose increments or decrements over 12 weeks	12 weeks
Secondary	Clinical global impression scoring	To evaluate for clinical status according to the clinical global impression scale. Clinical global impression is presented in a scale of 1-7. High score denotes a worse outcome.	12 weeks
Secondary	Mini-mental state score	The change in cognition as assessed by mini-mental state examination on a 30-point questionnaire at 12 weeks from baseline. Minimum and maximum score on this scale is 0 and 30. Lower score denotes worse outcome.	Baseline and 12 weeks
Secondary	Serum clozapine level	To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks.	Baseline and 12 weeks
Secondary	Incidence of treatment-emergent adverse events	To evaluate and compare the incidence of treatment-emergent adverse events in both groups.	12 weeks