A Placebo-controlled Efficacy Study of IV Ceftriaxone for Refractory Psychosis
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|ClinicalTrials.gov Identifier: NCT00591318|
Recruitment Status : Unknown
Verified September 2009 by Research Foundation for Mental Hygiene, Inc..
Recruitment status was: Recruiting
First Posted : January 11, 2008
Last Update Posted : September 18, 2009
Many patients with schizophrenia and schizoaffective disorder have symptoms that persist, including hallucinations or delusions, despite adequate pharmacotherapy with antipsychotic drug. Glutamate is a major excitatory neurotransmitter in the brain that has been implicated in several brain diseases. NMDA antagonist drugs cause symptoms of psychosis in otherwise normal persons. It is postulated that reduced NMDA receptor mediated neurotransmission leads to an increase in synaptic glutamate. Excessive synaptic concentrations of glutamate can produce excitatory neurotoxicity. Agents which reduce excess glutamate activity are neuroprotective. This therapeutic strategy has been applied to schizophrenia through the use of compounds that reduce presynaptic release of glutamate or otherwise decrease excessive postsynaptic stimulation, including lamotrigine, memantine and a m-GLU-R2 agonist (LY354740) with the hypothesized result of a reduction in psychotic symptoms.
Recently it was shown that a commonly available antibiotic (ceftriaxone) has the unique neuroprotective function of decreasing the amount of extracellular glutamate in nervous system tissue by increasing the number of glutamate transporter proteins. Our clinical experience with patients who have refractory psychosis and past Lyme disease indicates that in some patients psychosis may improve with IV ceftriaxone therapy. Whether this improvement was due to its antimicrobial or glutamate effect or a placebo effect is uncertain. In a placebo-controlled design, this study investigates the ability of ceftriaxone to decrease psychotic symptoms in patients with refractory psychotic disorders. In addition, the study will examine glutamatergic functional activity before and after treatment using brain imaging with magnetic resonance spectroscopy.
|Condition or disease||Intervention/treatment||Phase|
|Psychosis Schizophrenia Schizoaffective Disorder||Drug: ceftriaxone Drug: Normal Saline||Phase 1 Phase 2|
Patients will be screened over the telephone. Information will be gathered from the mental health treatment team and the patient. Most patients who come to this study have had an inadequate or insufficient improvement with clozapine. Upon arrival at the NYS Psychiatric Institute, they review and sign consent to make sure the details of the research study are understood. Comprehensive assessments are conducted, including neurocognitive testing, prior to treatment onset. The treatment is randomized so patients will either receive IV ceftriaxone or IV placebo. Treatment is given Monday through Friday to enable the patient to have weekends off without a plastic tube (angiocath) in the vein of the arm. If after 6 weeks the patient's symptoms are not at least mildly improved, then the treatment will be stopped. If however there are signs of improvement, the treatment will be continued another 2 weeks. If at the end of the "double-blind" part of the study a patient learns he/she received placebo and wishes to be given ceftriaxone, we will provide 4 weeks of ceftriaxone for those patients. The inpatient unit is located in the NYS Psychiatric Institute which is adjacent to the Columbia Medical Center in northern Manhattan. Our new building for the NYS Psychiatric Institute is about 10 years old so the inpatient unit is quite attractive with beautiful views of the Hudson River and the Palisades. There is no financial cost for the inpatient stay nor is there a financial cost for participating in this study.
Patients or family members wishing to learn more about this research study should call 212-543-6510 for more information or call Dr. Fallon directly at 212-543-5487.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||IV Ceftriaxone for Refractory Psychosis: a Controlled Trial|
|Study Start Date :||August 2007|
|Estimated Primary Completion Date :||August 2010|
IV Ceftriaxone 2 grams/day
2 grams of ceftriaxone given daily, Monday to Friday, excluding major holidays, for a total of 40 doses
Other Name: "Rocephin"
Placebo Comparator: B
IV Placebo (Normal Saline)
Drug: Normal Saline
50 cc of normal saline, daily, Monday through Friday, except for major holidays, for a total of 40 normal saline infusions.
- PANNS Score (Total and Positive Symptom) [ Time Frame: Baseline, 2, 4, 6 & 8 weeks ]
- MR Spectroscopy [ Time Frame: Baseline and 8 weeks ]
- MATRICS [ Time Frame: Baseline and End of Treatment ]
- SAPS/SANS [ Time Frame: Baseline and Wk 8 ]
- Hamilton Depression Scale [ Time Frame: Baseline and Week 8 ]
- Side Effect Checklist [ Time Frame: Baseline & weekly through Wk 8 ]
- Hamilton Anxiety Scale [ Time Frame: Baseline, weeks 2, 4, 6, 8 ]
- MMSE [ Time Frame: Baseline and week 8 ]
- CDSS [ Time Frame: Baseline, weeks 2, 4, 6, 8 ]
- CGI Change [ Time Frame: Weekly through week 8 ]
- YMRS [ Time Frame: Baseline and Week 8 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00591318
|Contact: Katy M Harper, M.A.||firstname.lastname@example.org|
|United States, New York|
|NYS Psychiatric Institute||Recruiting|
|New York, New York, United States, 10032|
|Principal Investigator: Brian A Fallon, MD|
|Sub-Investigator: Jeffrey Lieberman, MD|
|Sub-Investigator: Lawrence Kegeles, MD|
|Principal Investigator:||Brian A Fallon, MD||New York State Psychiatric Institute|