SchizophreniaPhase 2/3DMNCT01189006
Add-On Therapy to Risperidonein Schizophrenia
A Phase 2/3 study testing Dextromethorphan in people with Schizophrenia, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Dextromethorphan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2005to Dec 2008
- Phase
- Phase 2/3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patient aged ≧18 and ≦60 years.
- A diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV criteria made by a specialist in psychiatry.
- Acute exacerbation of schizophrenia.
- A total of PANSS score of at least 60 at screen.
- History of schizophrenia ≦ 15 years (from onset of prodromal symptoms).
- Signed informed consent by patient or legal representative
- Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.
Who cannot join
- Women of childbearing potential not using adequate contraception as per investigator judgement or not willing to comply with contraception for duration of study.
- Less than a full cycle has lapsed at time of screening following the last injection of a depot antipsychotic
- Females who are pregnant or nursing.
- Patient has received dextromethorphan, or other selective cyclo- oxygenase 2 inhibitors, or other anti-inflammatory medication within 1 week prior to first dose of double-blind medication.
- Axis-I DSM-IV diagnosis other than schizophrenia or schizoaffective disorder.
- Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that in the judgement of the investigator, would compromise patient safety or preclude study participation.
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- History of intolerance to risperidone or dextromethorphan or other Cox-2 inhibitors.
- History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) precipitated by dextromethorphan.
- Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to first dose of double-blind medication.
- Diagnosis of or treatment for oesophageal, gastric, pyloric channel, or duodenal ulceration or related complications (bleeding and/or perforation) within 30 days prior to receiving first dose of double-blind medication.
- Inclusion in another schizophrenia study or study for another indication with psychotropics within the last 30 days prior to start of study.
- Increase in total SGOT, SGPT, gamma-GT, BUN and creatinine by more than 3X ULN (upper limit of normal).
- History of idiopathic or drug-induced agranulocytosis.
- Alcohol, illegal or other substance-abuse within 6 months prior to study start, as defined by DSM-IV criteria.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Placebo-Controlled, Randomized Study of the Efficacy of Dextromethorphan as Add-On Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia
These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor.
Read the detailed description
Liu et al. (2003) have reported that DM protected dopamine (DA) neurons against inflammation-mediated degeneration. Zhang et al.'s (2004) novel finding was that 1-10 μM DM protected DA neurons against LPS (10 ng/mL)-induced reduction of DA uptake functionally in rat primary mixed mesencephalic neuron-glia cultures. Morphologically, in lipopolysaccharide (LPS)-treated cultures, in addition to the reduction of abundance of DA neurons, the dendrites of the remaining DA neurons were significantly less elaborate than those of controls. In cultures pretreated with DM (10 μM) before LPS stimulation, DA neurons were significantly more numerous and the dendrites less affected. Significant neuroprotective was observed in cultures with DM added up to 60 minutes after the addition of LPS. Thus, DM significantly protects DA neurons not only with pretreatment but also with post-treatment (Zhang et al. 2004). The mechanism of the neuronprotective effect of DM is associated with the inhibition of microglia activation but not with its NMDA receptor antagonist property. Zhang et al. (2005) have examined several N-methyl-D-aspartate (NMDA) receptor antagonists, including MK801, AP5, and memantine. Results from these studies indicate that among these compounds tested there was no correlation between the affinity of NMDA receptor antagonist activity and potency of the neuroprotective on DA neurons. On the contrary, a better correlation was found between the anti-inflammatory potency and the neuron protection. These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor. This conclusion is not in conflict with the previous reports, indicating that NMDA receptor blockade is associated with the neuroprotective effect of DM in acute glutamate-induced excitotoxicity models. The above evidences of benefit on auto-immune system with dextromethorphan would support that dextromethorphan as add-on therapy to atypical antipsychotics might be more effective than atypical antipsychotics alone on improvement of both positive and negative symptoms in schizophrenia.
- Conditions
- Schizophrenia
- Being tested
- Dextromethorphan
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethorphanDrug
Add-On double-blind study treatment commenced at randomization for 11 weeks while patients were continuing open-label risperidone. Randomization was immediately preceded by a one week open-label Risperidone-Only Treatment period. Patients who were receiving antipsychotics medication(s) at screen other than risperidone alone was withdrawn from previous non-risperidone medication(s) and at the same time commenced risperidone in titrating doses over a week. This Antipsychotic Switch-Over Period occurred between Screen and Risperidone-Only Treatment period. Patients remained hospitalized for at least during the Risperidone-Only treatment Period and first week of Add-On treatment Period.
| Study group | Role | What they receive |
|---|---|---|
| dextromethorphan | Experimental | Research clinical trial of double-blind, stratified randomized, parallel group, double-centre study Receives: Drug: Dextromethorphan |
What is being measured
The primary outcome is the main question the study is designed to answer.
positive and negative symptoms in schizophrenia
Measured: baseline
positive and negative symptoms in schizophrenia
Measured: week1
positive and negative symptoms in schizophrenia
Measured: week2
positive and negative symptoms in schizophrenia
Measured: week4
positive and negative symptoms in schizophrenia
Measured: week6
positive and negative symptoms in schizophrenia
Measured: week8
positive and negative symptoms in schizophrenia
Measured: week11
Secondary outcomes (3)
Specific Serum Immunological Parameters
SGOT, SGPT, gamma-GT, BUN and creatinine
Measured: baseline
Specific Serum Immunological Parameters
Measured: week11
lipid profiles
Measured: based line, after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2010 (estimated)
- Study startJan 2005
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ru-Band Lu, MD, Principal investigator, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01189006
- Sponsor's protocol ID
- DM-Schizo
- Other IDs
- Taiwan NIH
- Acronym
- DM
- Status last verified
- Aug 2010
- First submitted
- 23 Aug 2010
- Last updated
- 28 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chen SL, Lee SY, Chang YH, Chen SH, Chu CH, Tzeng NS, Lee IH, Chen PS, Yeh TL, Huang SY, Yang YK, Lu RB, Hong JS. Inflammation in patients with schizophrenia: the therapeutic benefits of risperidone plus add-on dextromethorphan. J Neuroimmune Pharmacol. 2012 Sep;7(3):656-64. doi: 10.1007/s11481-012-9382-z. Epub 2012 Jun 23.
PubMed 22730040
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Placebo-Controlled, Randomized Study of the Efficacy of Dextromethorphan as Add-On Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT01189006
- Acronym / sponsor ID
- DM / DM-Schizo
- Conditions
- Schizophrenia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 26 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor.
Detailed description
Liu et al. (2003) have reported that DM protected dopamine (DA) neurons against inflammation-mediated degeneration. Zhang et al.'s (2004) novel finding was that 1-10 μM DM protected DA neurons against LPS (10 ng/mL)-induced reduction of DA uptake functionally in rat primary mixed mesencephalic neuron-glia cultures. Morphologically, in lipopolysaccharide (LPS)-treated cultures, in addition to the reduction of abundance of DA neurons, the dendrites of the remaining DA neurons were significantly less elaborate than those of controls. In cultures pretreated with DM (10 μM) before LPS stimulation, DA neurons were significantly more numerous and the dendrites less affected. Significant neuroprotective was observed in cultures with DM added up to 60 minutes after the addition of LPS. Thus, DM significantly protects DA neurons not only with pretreatment but also with post-treatment (Zhang et al. 2004). The mechanism of the neuronprotective effect of DM is associated with the inhibition of microglia activation but not with its NMDA receptor antagonist property. Zhang et al. (2005) have examined several N-methyl-D-aspartate (NMDA) receptor antagonists, including MK801, AP5, and memantine. Results from these studies indicate that among these compounds tested there was no correlation between the affinity of NMDA receptor antagonist activity and potency of the neuroprotective on DA neurons. On the contrary, a better correlation was found between the anti-inflammatory potency and the neuron protection. These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor. This conclusion is not in conflict with the previous reports, indicating that NMDA receptor blockade is associated with the neuroprotective effect of DM in acute glutamate-induced excitotoxicity models. The above evidences of benefit on auto-immune system with dextromethorphan would support that dextromethorphan as add-on therapy to atypical antipsychotics might be more effective than atypical antipsychotics alone on improvement of both positive and negative symptoms in schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dextromethorphan | Experimental | Drug: DextromethorphanResearch clinical trial of double-blind, stratified randomized, parallel group, double-centre study |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patient aged ≧18 and ≦60 years.
- A diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV criteria made by a specialist in psychiatry.
- Acute exacerbation of schizophrenia.
- A total of PANSS score of at least 60 at screen.
- History of schizophrenia ≦ 15 years (from onset of prodromal symptoms).
Key exclusion criteria (14 listed)
- Women of childbearing potential not using adequate contraception as per investigator judgement or not willing to comply with contraception for duration of study.
- Less than a full cycle has lapsed at time of screening following the last injection of a depot antipsychotic
- Females who are pregnant or nursing.
- Patient has received dextromethorphan, or other selective cyclo- oxygenase 2 inhibitors, or other anti-inflammatory medication within 1 week prior to first dose of double-blind medication.
- Axis-I DSM-IV diagnosis other than schizophrenia or schizoaffective disorder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DextromethorphanAdd-On double-blind study treatment commenced at randomization for 11 weeks while patients were continuing open-label risperidone. Randomization was immediately preceded by a one week open-label Risperidone-Only Treatment period. Patients who were receiving antipsychotics medication(s) at screen other than risperidone alone was withdrawn from previous non-risperidone medication(s) and at the same time commenced risperidone in titrating doses over a week. This Antipsychotic Switch-Over Period occurred between Screen and Risperidone-Only Treatment period. Patients remained hospitalized for at least during the Risperidone-Only treatment Period and first week of Add-On treatment Period. | Drug | dextromethorphan |
Primary outcome
positive and negative symptoms in schizophrenia
Time frame: baseline
positive and negative symptoms in schizophrenia
Time frame: week1
positive and negative symptoms in schizophrenia
Time frame: week2
positive and negative symptoms in schizophrenia
Time frame: week4
positive and negative symptoms in schizophrenia
Time frame: week6
positive and negative symptoms in schizophrenia
Time frame: week8
positive and negative symptoms in schizophrenia
Time frame: week11
3 secondary outcomes
Specific Serum Immunological Parameters
Time frame: baseline
Specific Serum Immunological Parameters
Time frame: week11
lipid profiles
Time frame: based line, after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2013.
- Derived from this study: PubMed 22730040Chen SL, Lee SY, Chang YH, Chen SH, Chu CH, Tzeng NS, Lee IH, Chen PS, Yeh TL, Huang SY, Yang YK, Lu RB, Hong JS. Inflammation in patients with schizophrenia: the therapeutic benefits of risperidone plus add-on dextromethorphan. J Neuroimmune Pharmacol. 2012 Sep;7(3):656-64. doi: 10.1007/s11481-012-9382-z. Epub 2012 Jun 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ru-Band Lu, MD principal investigator
National Cheng-Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dextromethorphan in people with Schizophrenia, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 7 inclusion and 14 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 28 Feb 2013. 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 Taiwan. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
positive and negative symptoms in schizophrenia (time frame: baseline). The study lists 7 primary outcomes in all. 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 NCT01189006, which also lists 1 linked publication.
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 28 Feb 2013.