L-Theanine in the Management of Schizophrenia

The Value of Augmenting L-Theanine in the Management of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Dietary supplement: L-Theanine; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Be'er Sheva, Israel
    • Be'er Sheva Mental Health Center
  • Hadera, Israel, 38814
    • Sha'ar Menashe Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; caps.
Experimental: L-Theanine	Dietary supplement: L-Theanine; 400 mg/day, caps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Clinical Global Impression Scale	every two weeks
The Positive and Negative Syndrome Scale	every two weeks
The Scale for the Assessment of Negative Symptoms	every two weeks
The Calgary Depression Scale for Schizophrenia	every two weeks
The Hamilton Scale for Anxiety	every two weeks
Cambridge Neuropsychological Test Automated Battery (CANTAB)	every 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The Global Assessment of Functioning	every two weeks
The Talbieh Brief Distress Inventory	every two weeks
The State/Trait Anxiety Inventory	every two weeks
The Quality of Life Scale	every two weeks
The Quality of Life Enjoyment and Satisfaction Questionnaire	every two weeks
The Extrapyramidal Symptom Rating Scale	every two weeks
Barnes Akathisia Scale	every two weeks

Collaborators and Investigators

• Sponsor: Sha'ar Menashe Mental Health Center
• Collaborators: Stanley Medical Research Institute; Beersheva Mental Health Center
• Investigators: Study Director: Chanoch Miodownik, MD, Be'er Sheva Mental Health Center; Principal Investigator: Michael S Ritsner, MD, PhD, Sha'ar Menashe Mental Health Center; Study Director: Yael Ratner, MD, Sha'ar Menashe Mental Health Center; Study Director: Anatoly Gibel, MD, Sha'ar Menashe Mental Health Center; Study Director: Tatyana Shleifer, MD, Be'er Sheva Mental Health Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 5, 2006
• First Submitted That Met QC Criteria: September 5, 2006
• First Posted (Estimate): September 6, 2006

Study Record Updates

• Last Update Posted (Estimate): December 16, 2008
• Last Update Submitted That Met QC Criteria: December 15, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Schizophrenia; Augmentation; Schizoaffective disorders; Theonine
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: Theanine 10/2006.ctil