Genetic Expression in Schizophrenics Treated With SSRI Augmentation: Relationship to Clinical and Cognitive Function

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by Sha’ar Menashe Mental Health Center.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Sha’ar Menashe Mental Health Center
ClinicalTrials.gov Identifier:
NCT00645580
First received: March 23, 2008
Last updated: February 18, 2009
Last verified: March 2008
  Purpose

In our study we aim to examine the effect of SSRI augmentation on negative symptoms and cognitive function in schizophrenia patients as well as to examine the effect of SSRI augmentation on the RNA and protein products in peripheral mononuclear cells (PMC). Finally, we aim to relate changes in PMC elements to changes in clinical symptoms and cognitive function. Our study hypotheses are that SSRI augmentation of anti-psychotic treatment in schizophrenia patients will improve negative symptoms as well as cognitive symptoms and that this improvement will be related to biochemical changes identifiable in PMC elements.


Condition Intervention
Schizophrenia
Drug: Fluvoxamine

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Alterations in mRNA and Protein Expression in Human Peripheral Mononuclear Blood Cells (PMC) of Schizophrenia Patients Treated With Fluvoxamine Augmentation of Antipsychotics: Relationship to Clinical Symptoms and Cognitive Function

Resource links provided by NLM:


Further study details as provided by Sha’ar Menashe Mental Health Center:

Primary Outcome Measures:
  • Schedule for the Assessment of Negative Symptoms (SANS) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Schedule for the Assessment of Positive Symptoms (SAPS) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Simpson Angus Scale for Extrapyramidal Side Effects (SA) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Abnormal Involuntary Movement Scales (AIMS) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Calgary Depression Scale [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Mini Mental State Examination [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Dot test (Keefe et al., 1997) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Digit Span (Wechsler, 1998) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Finger Tap Test (Reitan and Davison, 1974) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Wechsler memory tests (Wechsler, 1998) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
  • Computerized Cognitive Neuropsychological Battery (Silver et al 2003) [ Time Frame: 0 weeks, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: April 2008
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Fluvoxamine
Fluvoxamine 100mg/day PO for 6 weeks.
Other Names:
  • Favoxil
  • Luvox
  • Dumyrox
  • Fevarin
  • Faverin

Detailed Description:

Clinical studies have shown that adding selective serotonin reuptake inhibitor (SSRI) antidepressants to antipsychotics can improve negative symptoms of schizophrenia in patients unresponsive to antipsychotics alone (Silver and Nassar, 1992; Spina et al., 1994; Goff et al., 1995). However, the effect of SSRI augmentation on cognitive impairments of the illness has not been adequately tested.

The mechanism of SSRI augmentation is not known and is the focus of research interest.

We have recently shown that in animals, combined treatment of SSRI antidepressant and antipsychotic drug resulted in biochemical changes, different from the effects of the individual medications. Changes unique to the combined treatment were found in GABAergic components (GABA-Aβ3 receptor, glutamic acid decarboxylase 67 and PKCβ (Chertkow et al., 2005)) and changes unique to the combined treatment were found in selected areas of rat brain.

Studies of drug mechanisms in humans have utilized blood products and PMC which are readily accessible and may reflect molecular processes in the central nervous system (CNS) of schizophrenic patients (Kronfol and Remick, 2000; Avissar et al., 2001; Ilani et al., 2001; Rothermundt et al., 2001). In a recent study (Chertkow et al., 2007) which examined the gene expression profile of PMC's from antipsychotic-treated patients before the addition of the SSRI fluvoxamine, we found that mRNA expression of chemokine receptors, IL8RA and CCR1, and of RGS7 was significantly down-regulated following fluvoxamine augmentation. Additionally, the clinical assessments showed improvement in negative symptoms following the combined treatment. These findings suggested that gene expression changes in PMC's may be useful in investigating the mechanism of drug action in schizophrenia.

In this study we will examine RNA and protein expression in the course of fluvoxamine augmentation treatment. 15 chronic schizophrenic patients who have persistent negative symptoms and cognitive impairment despite adequate treatment will participate. Fluvoxamine 100mg/day will be added to the treatment regimen and continued for 6 weeks. Clinical state will be assessed using validated rating scales and cognitive performance will be assessed with a cognitive test battery. Blood samples will be taken at baseline and at 1, 3 and 6 weeks. The PMC's will be assayed using microarray, RT PCR and proteomic techniques. Changes in RNA and protein expression will be detected and compared with changes in clinical symptoms and cognitive function. Identification of biochemical changes related to augmentation treated and their relation to symptomatic and cognitive changes will be the major potential benefit of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65
  • A diagnosis of schizophrenia (DSM-IVTR)
  • Antipsychotic dose unchanged for at least 2 weeks prior to study
  • SANS score>= 3 on at least one of the global measures of affective blunting, alogia or avolition.
  • Knowledge of Hebrew

Exclusion Criteria:

  • Dementia or other serious neurological disorders
  • History of alcohol or drug use
  • Patients with a legal guardian
  • Patients involuntarily hospitalized by order of the district psychiatrist
  • Use of antidepressants within 1 month of the study
  • Renal or hepatic disorder
  • Patients with upper GI bleeds
  • Patients with SIADH syndrome
  • Pregnant woman

Criteria for the cessation of the study after initial commencement:

  • Severe adverse events (including but not only GI, cardiovascular, neurologic, hematologic or urologic severe adverse events)
  • Emergent suicidality
  • Emergence of hypomanic or manic symptoms
  • If the subject requests to stop
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00645580

Locations
Israel
Sha'ar Menashe Mental Health Center
Mobile Post Hefer, Israel, 37806
Sponsors and Collaborators
Sha’ar Menashe Mental Health Center
Investigators
Principal Investigator: Henry Silver, PhD Sha'ar Menshae Mental Health Center
  More Information

Publications:
Guy W (ed). National Institute of Mental Health. Abnormal Involuntary Movement Scale (AIMS). Early Clinical Drug Evaluation Unit Assessment Manual. Rockville, Maryland: US Department of Health and Human Services, 1976; pp. 534-537
Wechsler D. Wechsler Adult Intelligence Scale Manual. New York, New York: Guilford Press, 1998; pp. 95-188

Responsible Party: Prof. Henry Silver, Sha'ar Menashe Mental Health Center
ClinicalTrials.gov Identifier: NCT00645580     History of Changes
Other Study ID Numbers: 1-3-08
Study First Received: March 23, 2008
Last Updated: February 18, 2009
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Fluvoxamine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on August 18, 2014