Clinical trial NCT00372151: L-Theanine in the Management of Schizophrenia
Official title: The Value of Augmenting L-Theanine in the Management of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Schizoaffective disorders
Theonine
Augmentation
Lead sponsor: Sha'ar Menashe Mental Health Center
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: Beersheva Mental Health Center
First posted: 2006-09-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the proposed study is to investigate the efficacy and safety of add-on gamma-glutamylethylamide (L-theanine) versus a placebo for antipsychotic treatment for 8 weeks in a randomized, double-blind, parallel group study of 60 patients with schizophrenia and schizoaffective disorders.

Detailed description: This is a two-year randomized placebo-controlled double-blind investigation of the use of augmentative L-theanine in the management of 60 patients with schizophrenia and schizoaffective disorders. We will investigate several outcome variables in these patients including the positive and negative symptoms, affective features, emotional distress, neuropsychological testing, side effects, and the quality of life. Participating subjects on stable antipsychotic treatment will be randomized to receive for 8 weeks either L-theanine (400 mg/day) or a placebo in addition to regular ongoing antipsychotic medication for 8 weeks. Subjects will be assessed at baseline and after 2, 4, 6, and 8 weeks of treatment using psychiatric rating scales, self-reported questionnaires, and a neuropsychological battery of tests. The efficacy and safety of augmenting antipsychotic treatment with L-theanine will be analyzed.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) will be administered at commencement and completion of the study. The CANTAB battery consists of a series of interrelated computerized tests of visual and movement skills, attention and memory, and executive function, administered via a touch sensitive screen. The nonverbal nature of the CANTAB tests makes them largely language independent and culture free. These tests are run on an IBM-compatible personal computer with a touch-sensitive screen. Neuropsychological testing lasts approximately 2 hours. Subjects complete the tests in a fixed order with a break half-way through the testing session. For a description of the nature of these tests, the performance measures used, and how the test scores are derived, see (http://www.cantab.com/cantab/site/home.acds). The neuropsychological tests are categorized onto five cognitive domains: visual and movement skills, attention, memory, learning, sustained attention, and executive function: Motor Screening, Big/Little Circle, Reaction Time, Matching to Sample Visual Search, Delayed Matching to Sample, Pattern Recognition Memory, Spatial Recognition Memory, Spatial Span, Rapid visual information processing, Spatial working memory, Intra/Extra Dimensional Set Shift, and Stockings of Cambridge. In addition to raw scores from these tasks, the average value of the z-scores of the CANTAB neurocognitive tasks will be used to determine cognitive indices in specific domains.

Eligibility criteria: Inclusion Criteria:

* Age 18-60 years, men or women
* DSM-IV criteria for schizophrenia or schizoaffective disorder
* At least 4 on the Clinical Global Impression Scale
* At least two weeks of ongoing treatment with current antipsychotic agents.
* Ability and willingness to sign an informed consent form for participation in the study.

Exclusion Criteria:

* Evidence of serious neurologic or endocrine disorder, for example severe head trauma, seizure disorder, dementia, Cushings disease, or thyroid disorder, mental retardation, alcohol or drug abuse.
* Renal disease
* Hepatic dysfunction
* Pregnant women
* Patients receiving mood stabilizing medications.

Primary outcomes:
measure: The Clinical Global Impression Scale
timeFrame: every two weeks
measure: The Positive and Negative Syndrome Scale
timeFrame: every two weeks
measure: The Scale for the Assessment of Negative Symptoms
timeFrame: every two weeks
measure: The Calgary Depression Scale for Schizophrenia
timeFrame: every two weeks
measure: The Hamilton Scale for Anxiety
timeFrame: every two weeks
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: every 4 weeks
Secondary outcomes:
measure: The Global Assessment of Functioning
timeFrame: every two weeks
measure: The Talbieh Brief Distress Inventory
timeFrame: every two weeks
measure: The State/Trait Anxiety Inventory
timeFrame: every two weeks
measure: The Quality of Life Scale
timeFrame: every two weeks
measure: The Quality of Life Enjoyment and Satisfaction Questionnaire
timeFrame: every two weeks
measure: The Extrapyramidal Symptom Rating Scale
timeFrame: every two weeks
measure: Barnes Akathisia Scale
timeFrame: every two weeks
Other outcomes:
Locations:
city: Be'er Sheva
country: Israel
facility: Be'er Sheva Mental Health Center
city: Hadera
country: Israel
facility: Sha'ar Menashe Mental Health Center
Study officials:
affiliation: Sha'ar Menashe Mental Health Center
name: Michael S Ritsner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sha'ar Menashe Mental Health Center
name: Yael Ratner, MD
role: STUDY_DIRECTOR
affiliation: Sha'ar Menashe Mental Health Center
name: Anatoly Gibel, MD
role: STUDY_DIRECTOR
affiliation: Be'er Sheva Mental Health Center
name: Chanoch Miodownik, MD
role: STUDY_DIRECTOR
affiliation: Be'er Sheva Mental Health Center
name: Tatyana Shleifer, MD
role: STUDY_DIRECTOR
References:
citation: Yamada T, Terashima T, Okubo T, Juneja LR, Yokogoshi H. Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr Neurosci. 2005 Aug;8(4):219-26. doi: 10.1080/10284150500170799.
citation: Yokogoshi H, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines, striatal dopamine release and some kinds of behavior in rats. Nutrition. 2000 Sep;16(9):776-7. doi: 10.1016/s0899-9007(00)00384-1. No abstract available.
citation: Miodownik C, Maayan R, Ratner Y, Lerner V, Pintov L, Mar M, Weizman A, Ritsner MS. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol. 2011 Jul-Aug;34(4):155-60. doi: 10.1097/WNF.0b013e318220d8c6.
citation: Ritsner MS, Miodownik C, Ratner Y, Shleifer T, Mar M, Pintov L, Lerner V. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry. 2011 Jan;72(1):34-42. doi: 10.4088/JCP.09m05324gre. Epub 2010 Nov 30.