Back to resultsDextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
Primary Purpose
Treatment Resistant Schizophrenia
Status
Recruiting
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Dextromethorphan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Treatment Resistant Schizophrenia
Eligibility Criteria
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
Sites / Locations
- All India Institute of Medical Sciences (AIIMS)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Add-on Dextromethorphan
Add-on Placebo
Arm Description
Dextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.
Matched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Incidence of clozapine resistance
To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy.
Requirement of clozapine dose modification
To evaluate the proportion of patients requiring clozapine dose increments or decrements over 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.
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.
Serum clozapine level
To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks.
Incidence of treatment-emergent adverse events
To evaluate and compare the incidence of treatment-emergent adverse events in both groups.
Full Information
NCT ID
NCT05944510
First Posted
July 6, 2023
Last Updated
September 19, 2023
Sponsor
All India Institute of Medical Sciences, Bhubaneswar
1. Study Identification
Unique Protocol Identification Number
NCT05944510
Brief Title
Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
Official Title
Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia: A Randomized, Group Sequential Adaptive Design, Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2023 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
All India Institute of Medical Sciences, Bhubaneswar
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Schizophrenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Add-on Dextromethorphan
Arm Type
Experimental
Arm Description
Dextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.
Arm Title
Add-on Placebo
Arm Type
Placebo Comparator
Arm Description
Matched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.
Intervention Type
Drug
Intervention Name(s)
Dextromethorphan
Intervention Description
Dextromethorphan 30mg will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.
Primary Outcome Measure Information:
Title
Positive and negative symptom scale score
Description
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.
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Responder rate
Description
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.
Time Frame
12 weeks
Title
Incidence of clozapine resistance
Description
To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy.
Time Frame
12 weeks
Title
Requirement of clozapine dose modification
Description
To evaluate the proportion of patients requiring clozapine dose increments or decrements over 12 weeks
Time Frame
12 weeks
Title
Clinical global impression scoring
Description
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.
Time Frame
12 weeks
Title
Mini-mental state score
Description
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.
Time Frame
Baseline and 12 weeks
Title
Serum clozapine level
Description
To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks.
Time Frame
Baseline and 12 weeks
Title
Incidence of treatment-emergent adverse events
Description
To evaluate and compare the incidence of treatment-emergent adverse events in both groups.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
RITUPARNA MAITI, M.D.
Phone
9438884191
Email
pharm_rituparna@aiimsbhubaneswar.edu.in
First Name & Middle Initial & Last Name or Official Title & Degree
BISWA R MISHRA, M.D.
Phone
9438884220
Email
psych_biswa@aiimsbhubaneswar.edu.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
DEBASISH HOTA, D.M.
Organizational Affiliation
AIIMS Bhubaneswar
Official's Role
Study Chair
Facility Information:
Facility Name
All India Institute of Medical Sciences (AIIMS)
City
Bhubaneswar
State/Province
Odisha
ZIP/Postal Code
751019
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
RITUPARNA MAITI, MD
Phone
9438884191
Email
pharm_rituparna@aiimsbhubaneswar.edu.in
First Name & Middle Initial & Last Name & Degree
BISWA R MISHRA, MD
Email
psych_biswa@aiimsbhubaneswar.edu.in
First Name & Middle Initial & Last Name & Degree
NAVEEN C HEGDE, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Necessary data can be requested from the principal investigator.
Citations:
PubMed Identifier
28655284
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.
Results Reference
background
PubMed Identifier
32594486
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.
Results Reference
background
PubMed Identifier
36463316
Citation
Kruse AO, Bustillo JR. Glutamatergic dysfunction in Schizophrenia. Transl Psychiatry. 2022 Dec 3;12(1):500. doi: 10.1038/s41398-022-02253-w.
Results Reference
background
PubMed Identifier
31254879
Citation
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.
Results Reference
background
PubMed Identifier
17461892
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.
Results Reference
background
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Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
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