Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

Study Overview
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Brief Summary
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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.

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

Conditions
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Treatment Resistant Schizophrenia

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Add-on Dextromethorphan<br>Dextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia. | Drug: Dextromethorphan<br>* Dextromethorphan 30mg will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.<br>|
| Placebo Comparator: Add-on Placebo<br>Matched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia. | Drug: Placebo<br>* Matched placebo will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Incidence of clozapine resistance | To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy. | 12 weeks | 
| Requirement of clozapine dose modification | To evaluate the proportion of patients requiring clozapine dose increments or decrements over 12 weeks | 12 weeks | 
| 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 | 
| 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 | 
| Serum clozapine level | To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks. | Baseline and 12 weeks | 
| Incidence of treatment-emergent adverse events | To evaluate and compare the incidence of treatment-emergent adverse events in both groups. | 12 weeks |