L-carnosine for Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional

Summary: 
      The investigators' hypothesis is that oral L-carnosine treatment (as compared with placebo)
      will enhance cognitive abilities (specifically: measures of attention, executive function,
      working memory, visuospatial ability and language) in persons with schizophrenia or
      schizoaffective disorder. Secondarily, they hypothesize that there will be secondary
      improvements in positive, negative and mood symptoms with L-carnosine treatment.

      The investigators aim to test these hypotheses by conducting a randomized, placebo
      controlled, add-on treatment trial of L-carnosine (added to existing antipsychotic treatment)
      up to 84 recruited subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th
      Edition, Text Revision (DSM-IV-TR) schizophrenia/schizoaffective disorder for a period of 16
      weeks. Measures of cognition and psychopathology will be utilized for evaluating primary and
      secondary outcomes, along with safety assessments.
    

Detailed description: 
      OBJECTIVE:

      Based on the available neuroscience and human data, we hypothesize that supplemental
      L-carnosine treatment (a potent naturally occuring antioxidant and anti-glycation agent) will
      be a useful disease modifying agent when used adjunctively with antipsychotic drugs in
      patients with a diagnosis of either schizophrenia or schizoaffective disorder. More
      specifically, our hypothesis is that oral L-carnosine treatment (as compared with placebo)
      will enhance cognitive abilities (specifically: measures of attention, executive function,
      working memory, visuospatial ability and language) in persons with schizophrenia or
      schizoaffective disorder. Secondarily, we hypothesize there will be secondary improvements in
      positive, negative and mood symptoms with L-carnosine treatment.

      RESEARCH PLAN:

      A randomized, placebo controlled, add-on treatment trial of L-carnosine (added to existing
      antipsychotic treatment) for a period of 16 weeks. Measures of cognition, and psychopathology
      will be utilized for evaluating primary and secondary outcomes, along with safety
      assessments.

      METHODS:

      Up to eighty-four subjects with DSM-IV-TR schizophrenia/schizoaffective disorder will be
      recruited from Western Psychiatric Institute and Clinic, Mayview State Hospital, Mon Yough
      Community Services, Inc. and Dubois Regional Medical Center using a 1:1 randomization,
      subjects who sign a informed consent document will be randomized to receive L-carnosine or
      placebo. During a 4 week titration period, the L-carnosine dosage will be increased from 500
      to 2000 mg/day, and continued for an additional 8 weeks. If side-effects are noted, a minimum
      of 500 mg/day of L-carnosine can be used.

      A computerized cognitive battery will form the main efficacy measures and be administered at
      baseline and at visit 6 (i.e. just prior to the 4 week taper); some of these measures will be
      administered at visit 4 (28 days). Standard psychopathology rating scales will be
      administered to evaluate secondary aims such as impact on positive and negative symptoms of
      schizophrenia. Safety will be assessed by tailing a careful medical history and physical
      examination at screening and evaluating results of laboratory measures. Any adverse effects
      will be assessed by asking questions at each visit, and if required bringing subjects in for
      assessments outside the scheduled visits.

      SIGNIFICANCE:

      Cognitive dysfunction in persons with schizophrenia is a serious limitation to achieving
      significantly better functional outcomes (Green, et. al., 1996). Till recently, therapeutic
      nihilism prevailed when it came to treatments that improve cognitive abilities in
      schizophrenia. One reason for this pessimistic view was that cognitive dysfunction was not
      considered to be malleable to treatment but instead was thought to represent an unchanging
      dimension of the illness. However, that view is now changing, and psychosocial and cognitive
      remediation techniques are being evaluated to treat cognitive dysfunction in schizophrenia. A
      recent synthesis of data would suggest that mediators of a better cognitive outcome may also
      include agents that target the inefficient antioxidant defenses in persons with
      schizophrenia, or those that counter NMDA-glutamate neuronal excitotoxicity (Yao et al.,
      2001). These mechanisms may underlie the neuronal membrane pathology in schizophrenia, and in
      turn these abnormalities may contribute to the cognitive dysfunction and decline reported
      during the course of the illness. The benefits of L-carnosine (a naturally occurring
      antioxidant and anti-glycation agent) for improved cognitive abilities and in social behavior
      and communicative skills were reported in a random-assignment, double-blind,
      placebo-controlled trial in children and adolescents with autism; specifically improvements
      in receptive language scores and socialization and communication skill scores (Chez et al.,
      2002a).

      The primary focus of this study is to evaluate the ability of L-carnosine, a naturally
      occurring dipeptide, to enhance cognitive abilities in people with schizophrenia. The study
      will also evaluate whether L-carnosine has secondary benefits for positive and negative and
      mood symptoms. As a relatively benign agent, L-carnosine offers the potential to achieve a
      significant clinical impact in improving cognitive dysfunction in persons with schizophrenia,
      if efficacy is confirmed.
    

Intervention name(s): L-carnosine (dietary supplement)
Intervention type(s): Drug
Intervention description(s): an antioxidant and AGE inhibitor, 500 mg/day, titration each week to reach 2000 mg/day in 4 weeks L-Carnosine is a dietary supplement
Other intervention name(s): L Carnosine; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: L-carnosine; Schizophrenia; Schizoaffective disorder; Cognitive enhancement