L-Carnosine for Bipolar I Disorder
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.
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.
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.
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.
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.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Bipolar I Disorder
Mayview State Hospital
University of Pittsburgh
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00177463
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.
An amino acid formed in vivo by the degradation of dihydrouracil and carnosine. Since neuronal uptake and neuronal receptor sensitivity to beta-alanine have been demonstrated, the compound may be a false transmitter replacing GAMMA-AMINOBUTYRIC ACID. A rare genetic disorder, hyper-beta-alaninemia, has been reported.
An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating BIPOLAR DISORDER.
INTERNEURONS of the vertebrate RETINA containing two processes. They receive inputs from the RETINAL PHOTORECEPTOR CELLS and send outputs to the RETINAL GANGLION CELLS. The bipolar cells also make lateral connections in the retina with the RETINAL HORIZONTAL CELLS and with the AMACRINE CELLS.
A naturally occurring dipeptide neuropeptide found in muscles.
The absorption kinetics of dietary carnosine (β-alanyl-L-histidine) will be determined in the healthy adults.
The main objective of this study is to assess the effectiveness and safety of lamotrigine in the treatment of youth with bipolar and bipolar spectrum disorder. This is an exploratory, 12-w...
Carnosine is a naturally occurring compound with a potential health benefits. In animal studies, carnosine supplementation reduces manifestation of chronic civilization diseases, regulates...
The purpose of this study is to look at certain structural changes in the brain in people with bipolar disorder or those with a history of Bipolar disorder. Also collecting a blood sample...
This is an open-label pilot study of up to 1200 mg/day of carbamazepine ER (Equetro) in the treatment of children who meet DSM-IV criteria for Bipolar I, Bipolar II, or Bipolar Spectrum Di...
The results of mortality studies have indicated that medical conditions, such as cardiovascular disease, obesity and diabetes are the most important causes of mortality among patients with bipolar dis...
Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to d...
We aimed to analyzed the association between polymorphisms of the FKBP5 (FK506 binding protein 5) gene and subtypes of bipolar disorder. In the study, we included 195 bipolar disorder patients with ps...
While cognitive deficits have been well documented in patients with bipolar disorder, visual perception has been less well characterized. Such deficits appear in schizophrenia, which shares genetic ri...
Pediatric bipolar disorder is a severe mental illness whose pathophysiology is poorly understood and for which there is an urgent need for improved diagnosis and treatment. MR spectroscopy is a neuroi...