SchizophreniaPhase 4NCT02034474
Tocilizumab as Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia
A Phase 4 study testing Tocilizumab in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Randomized, double-blind clinical trial of tocilizumab vs. placebo as add-on treatment for residual positive, negative, and cognitive symptoms in schizophrenia. The primary study hypothesis is that individuals receiving tocilizumab will show greater improvements in their PANSS total scores than those taking placebo. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to 6 Feb 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Fulfill DSM-IV criteria for schizophrenic illness, schizoaffective disorder
- Negative urine toxicology
- Capacity to understand the study and give written informed consent
- Must be on a stable dose of antipsychotic medications, up to two medications, except for clozapine, for at least 4 weeks if oral or 2 cycles if depot. Mood stabilizers, benzodiazepines and antidepressants are allowed as long as no change for 4 weeks.
- Moderate level of symptomatology
Who cannot join
- Pregnancy or lactation, lack of effective birth control during the 15 days before the initial day of the study and for the duration of the drug trial
- Unstable medical or neurological condition (including chronic rashes other than mild eczema, ANC < 2000, platelet count < 120,000, severe liver disease or AST/ALT greater than 1.5 times the ULN at baseline, or any chronic inflammatory or immunologic disorder that impairs the immune system, a current severe infection, intestinal diverticula, or tuberculosis (latent or active-patients with a positive ppd but negative chest x ray may participate) or a live vaccine within one month of receiving study drug
- Any current non medicinal use of amphetamines, opiates, cocaine, sedative-hypnotics, cannabis, or other psychoactive drugs (other than nicotine)
- Currently taking a medication known to cause neutropenia (clozapine, carbamazepine), or another disease modifying anti-rheumatic drugs (DMARD)
- Any history of substance dependence (other than nicotine or cannabis) within the previous 6 months or a history of substance abuse within the previous 1 month (other than nicotine)
- Impaired intellectual functioning
Show all 36Show fewer
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer)
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline
- Previous treatment with tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on case-by-case basis
- Any previous treatment with alkylating agents such as chlorambucil, or with a total lymphoid irradiation
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease)
- Current liver disease
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks or oral antibiotics within 2 weeks
- Active TB requiring treatment within the previous 3 years.
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured) or breast cancer diagnosed within the previous 20 years
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
- Lack of peripheral venous access
- Body weight of >150 kg
- Serum creatinine > 1/6mg/dL (141 umol/L) in female patients and > 1.9 mg/dL (168 umol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are > 30
- Total Bilirubin >ULN
- Hemoglobin < 85g/L
- White Blood Cells <3.0 x 10^9/L
- Absolute Lymphocyte Count < 0.5 x 10^9/L
- Positive Hepatitis BsAg or Hepatitis C antibody
- Additional Exclusion Criteria for MRI portion
- Metal implants or a history of metal working
- Lifetime diagnosis of asthma with asthmatic symptoms within the past 3 years
- Lifetime diagnosis of renal failure or renal disease
- Lifetime diagnosis of hypertension or diabetes
- Renal insufficiency
- More than one previous gadolinium scan
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Tocilizumab, An IL-6 Receptor Antibody, As Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Randomized, double-blind clinical trial of tocilizumab vs. placebo as add-on treatment for residual positive, negative, and cognitive symptoms in schizophrenia. The primary study hypothesis is that individuals receiving tocilizumab will show greater improvements in their PANSS total scores than those taking placebo.
Read the detailed description
One of the main mediators of the effects of infection/inflammation in the human body is cytokines. Recent data suggest that cytokines, and in particular IL-6, may mediate the effects of lifetime or prenatal infection on schizophrenia risk. Preclinical models of schizophrenia support a convergence between a role for IL-6 in the pathophysiology of schizophrenia and the major neurochemical hypotheses of schizophrenia-the dopamine and glutamate hypotheses. Namely, IL-6 dysfunction or excess promotes schizophrenia-like behaviors and schizophrenia-like biochemical and electrophysiological profiles, while IL-6 knockout or neutralization mitigates these abnormalities. Furthermore, plasma IL-6 levels are elevated in acutely psychotic but not treated patients, and Positron Emission Tomography (PET) studies have shown active inflammation in the brains of individuals with psychosis. Finally, treatment of individuals with schizophrenia with non-specific anti-inflammatory agents, such as celecoxib and aspirin, has suggested a role for anti-inflammatory agents in schizophrenia. These data also suggest that studies of immunologic agents that more specifically target the underlying pathophysiology of schizophrenia may be more efficacious. Tocilizumab (Actemra®) is an FDA-approved humanized monoclonal antibody against the IL-6 receptor used for treatment of rheumatoid arthritis in individuals who have not responded to at least one TNF-alpha therapy and for juvenile idiopathic arthritis
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Tocilizumab, Placebo
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra
8mg/kg intravenously via iv drip over 60 min
PlaceboDrug
Also called Saline Drip
intravenously via iv drip over 60 min
| Study group | Role | What they receive |
|---|---|---|
| tocilizumab | Experimental | Tocilizumab will be administered at day 0, week 4 and week 8 via an iv drip over 60 min. Dose is 8mg/kg but may be reduced to 4mg/kg if intolerable. Maximum dose will be 800mg. Receives: Drug: Tocilizumab |
| Placebo | Placebo comparator | Placebo will be administered intravenously via an iv drip over 60 min Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response to Tocilizumab
To evaluate an anticipated clinical response to tocilizumab treatment including positive, negative and cognitive symptoms by the change in the Positive and Negative Syndrome Scale (PANSS) total score. Score ranges from 30 to 210 for PANSS total, 16-112 for General, 7-49 for positive and 7-49 for negative symptoms subscales. A lower score means less symptomatic. There is a total score and general psychopathology scores, a positive symptoms score and a negative symptom score. The unit of measure is units on a scale from 1-7, whole numbers only. Summed scores are simply added to each other
Measured: Baseline (start of tocilizumab) through 12 weeks. We present the change scores
Secondary outcomes (2)
Cognitive Symptomatology - Overall MATRICS t Score Change
MATRICS cognitive consensus battery, overall t score change. The composite T-score at each time point (baseline and week 12) is a T-Score (ranging from 0 to 100) reflecting overall neuropsychological function, aggregated from the participant's T-scores on the MATRICS subscales for Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. The outcome is the difference between overall composite T-score at baseline and week 12, with higher difference score reflecting a greater improvement in neuropsychological performance.
Measured: Baseline (start of tocilizumab) through 12 weeks
Cognitive Symptomatology - UPSA-B Score Change
At Baseline and Week 12, participants are UPSA-B given items reflecting ability to complete tasks encountered in daily life, across two domains, Financial Skills and Communication Skills. % correct is calculated for each domain and converted to a standardized score from 0-50. These scores are summed to produce a total summary score ranging from 0-100. The outcome is the difference between this summary score at Baseline and Week 12, with a higher difference score reflecting a greater increase in functional capacity.
Measured: Baseline (start of tocilizumab) through 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completion6 Feb 2017
- Study completion6 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Marlene Carlson, New York State Psychiatric Institute
- Investigators
- Ragy R Girgis, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02034474
- Sponsor's protocol ID
- 6729
- Status last verified
- Dec 2018
- First submitted
- 9 Jan 2014
- Last updated
- 26 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tocilizumab, An IL-6 Receptor Antibody, As Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT02034474
- Acronym / sponsor ID
- 6729
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Feb 2014 (actual)
- Primary completion
- 6 Feb 2017 (actual)
- Study completion
- 6 Feb 2017 (actual)
- First posted
- 13 Jan 2014 (estimated)
- Results
- Posted 26 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, double-blind clinical trial of tocilizumab vs. placebo as add-on treatment for residual positive, negative, and cognitive symptoms in schizophrenia. The primary study hypothesis is that individuals receiving tocilizumab will show greater improvements in their PANSS total scores than those taking placebo.
Detailed description
One of the main mediators of the effects of infection/inflammation in the human body is cytokines. Recent data suggest that cytokines, and in particular IL-6, may mediate the effects of lifetime or prenatal infection on schizophrenia risk. Preclinical models of schizophrenia support a convergence between a role for IL-6 in the pathophysiology of schizophrenia and the major neurochemical hypotheses of schizophrenia-the dopamine and glutamate hypotheses. Namely, IL-6 dysfunction or excess promotes schizophrenia-like behaviors and schizophrenia-like biochemical and electrophysiological profiles, while IL-6 knockout or neutralization mitigates these abnormalities. Furthermore, plasma IL-6 levels are elevated in acutely psychotic but not treated patients, and Positron Emission Tomography (PET) studies have shown active inflammation in the brains of individuals with psychosis. Finally, treatment of individuals with schizophrenia with non-specific anti-inflammatory agents, such as celecoxib and aspirin, has suggested a role for anti-inflammatory agents in schizophrenia. These data also suggest that studies of immunologic agents that more specifically target the underlying pathophysiology of schizophrenia may be more efficacious. Tocilizumab (Actemra®) is an FDA-approved humanized monoclonal antibody against the IL-6 receptor used for treatment of rheumatoid arthritis in individuals who have not responded to at least one TNF-alpha therapy and for juvenile idiopathic arthritis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tocilizumab | Experimental | Drug: TocilizumabTocilizumab will be administered at day 0, week 4 and week 8 via an iv drip over 60 min. Dose is 8mg/kg but may be reduced to 4mg/kg if intolerable. Maximum dose will be 800mg. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered intravenously via an iv drip over 60 min |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Fulfill DSM-IV criteria for schizophrenic illness, schizoaffective disorder
- Negative urine toxicology
- Capacity to understand the study and give written informed consent
- Must be on a stable dose of antipsychotic medications, up to two medications, except for clozapine, for at least 4 weeks if oral or 2 cycles if depot. Mood stabilizers, benzodiazepines and antidepressants are allowed as long as no change for 4 weeks.
- Moderate level of symptomatology
Key exclusion criteria (36 listed)
- Pregnancy or lactation, lack of effective birth control during the 15 days before the initial day of the study and for the duration of the drug trial
- Unstable medical or neurological condition (including chronic rashes other than mild eczema, ANC < 2000, platelet count < 120,000, severe liver disease or AST/ALT greater than 1.5 times the ULN at baseline, or any chronic inflammatory or immunologic disorder that impairs the immune system, a current severe infection, intestinal diverticula, or tuberculosis (latent or active-patients with a positive ppd but negative chest x ray may participate) or a live vaccine within one month of receiving study drug
- Any current non medicinal use of amphetamines, opiates, cocaine, sedative-hypnotics, cannabis, or other psychoactive drugs (other than nicotine)
- Currently taking a medication known to cause neutropenia (clozapine, carbamazepine), or another disease modifying anti-rheumatic drugs (DMARD)
- Any history of substance dependence (other than nicotine or cannabis) within the previous 6 months or a history of substance abuse within the previous 1 month (other than nicotine)
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 |
|---|---|---|
| TocilizumabAlso: Actemra8mg/kg intravenously via iv drip over 60 min | Drug | tocilizumab |
| PlaceboAlso: Saline Dripintravenously via iv drip over 60 min | Drug | Placebo |
Primary outcome
Clinical Response to Tocilizumab
Time frame: Baseline (start of tocilizumab) through 12 weeks. We present the change scores
To evaluate an anticipated clinical response to tocilizumab treatment including positive, negative and cognitive symptoms by the change in the Positive and Negative Syndrome Scale (PANSS) total score. Score ranges from 30 to 210 for PANSS total, 16-112 for General, 7-49 for positive and 7-49 for negative symptoms subscales. A lower score means less symptomatic. There is a total score and general psychopathology scores, a positive symptoms score and a negative symptom score. The unit of measure is units on a scale from 1-7, whole numbers only. Summed scores are simply added to each other
2 secondary outcomes
Cognitive Symptomatology - Overall MATRICS t Score Change
Time frame: Baseline (start of tocilizumab) through 12 weeks
Cognitive Symptomatology - UPSA-B Score Change
Time frame: Baseline (start of tocilizumab) through 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ragy R Girgis, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tocilizumab in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
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 5 inclusion and 36 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 26 Dec 2018. 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 United States. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 26 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Response to Tocilizumab (time frame: Baseline (start of tocilizumab) through 12 weeks. We present the change scores). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Dec 2018.