L-Carnosine for Bipolar I Disorder
Condition: Bipolar I Disorder
Study type: Interventional

Summary: 
      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 bipolar disorder. Secondarily, we
      hypothesize there will be secondary improvements in positive, negative and mood symptoms with
      L-carnosine treatment.

      We aim to test these hypotheses by conducting a randomized, placebo controlled, add on
      treatment trial of L-carnosine (added to existing antipsychotic treatment) on 48 recruited
      subjects with DSM IV TR bipolar disorder for a period of 12 weeks. Measures of cognition, and
      psychopathology will be utilized for evaluating primary and secondary outcomes, along with
      safety assessments.
    

Detailed description: 
      OBJECTIVE:

      It is our hypothesis that L-carnosine treatment of persons with bipolar illness will improve
      their cognitive outcomes, more specifically, measures of attention and executive function,
      verbal and visuospatial memory and psychomotor performance, relative to placebo treatment. We
      also hypothesize that L-carnosine treatment may secondarily improve any residual affective
      symptoms.

      RESEARCH PLAN:

      We aim to test these hypotheses by conducting a randomized, placebo controlled, add on
      treatment trial of L-carnosine (added to ongoing prescribed pharmacological treatment, for
      example - lithium, anticonvulsants, antipsychotic agents and depressants) for a period of 12
      weeks. Measures of cognition, and psychopathology will be utilized for evaluating primary and
      secondary outcomes, along with safety assessments.

      METHODS:

      Up to 48 subjects with DSM IV TR bipolar I disorder will be recruited from Western
      Psychiatric Institute and Clinic, Mayview State Hospital and Mon Yough Community Services,
      Inc. using a 1:1 randomization, subjects who sign a informed consent document will be
      randomized to receive L-carnosine or placebo.

      It is expected that 12 of the 48 subjects may not meet inclusion/exclusion criteria, leaving
      36 consenting adults (18 to 65 years) with DSM IV-TR Bipolar Disorder who will be assessed
      for euthymia (Young Mania Rating Scale Score ≤ 10, Montgomery Asberg Depression Rating Scale
      Score of ≤ 10) over a one month period (2 assessments) while receiving stable doses of their
      current medications. They will also be assessed for cognitive dysfunction
      (attention/executive function, immediate and declarative memory, and psychomotor performance)
      using Cogtest - a proprietary neuropsychological library of 19 tests. These subjects will be
      characterized for normal pre-morbid IQ, no ECT treatment in past 6 months, no alcohol or
      substance dependence in past 6 months, mini-mental state score ≥ 24.

      L-carnosine (or placebo) will be administered using random assignment at a dose of 500
      mg/day, increasing each week by 500 mg to a dose of 2000 mg/day (twice daily schedule) in 4
      weeks; as an adjunct to existing psychotropic medicines. The dose of 2000 mg (or less, i.e. a
      minimum of 500 mg if tolerability is an issue) will be continued for 8 additional weeks.
      L-carnosine is not known to have interactions with psychotropic drugs but mood-stabilizer
      levels will be monitored.

      Standard psychopathology rating scales will be administered to evaluate secondary aims such
      as impact on residual symptoms of bipolar disorder. 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 bring subjects in for assessments outside the scheduled visits, and by
      telephone contact in between longer scheduled visits.

      SIGNIFICANCE:

      Cognitive dysfunction can seriously hinder improved functional outcomes in persons with
      schizophrenia or bipolar disorder. If this short term intervention with L-carnosine shows
      promise, more definitive studies using adequate powered sample sizes, and of longer duration
      can be conducted. If improvements in cognitive problems are linked to improved functional
      outcomes using such supplemental treatments, an important therapeutic milestone in bipolar
      disorder will have been achieved.
    

Intervention name(s): L-carnosine
Intervention type(s): Drug
Intervention description(s): an antioxidant and AGE inhibitor, 500 mg/day, increasing each week in titration reaching 2000 mg/day in 4 weeks and maintained for rest of trial
Other intervention name(s): L Carnosine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: L-carnosine; Bipolar I disorder; Cognitive enhancement