Generalized Anxiety Disorder
Conditions
Keywords
Kava, Anxiety, Generalized Anxiety Disorder, Psychiatric, Anxiolytic, GABA, Kavalactones
Brief summary
The use of Kava in Generalised Anxiety Disorder: an 18-week double-blind, randomised, placebo-controlled study.
Detailed description
The primary aim is to confirm the efficacy and safety of Kava compared to placebo in Generalized Anxiety Disorder (GAD). Secondary aims of the study are to confirm the relationship between specific genetic variations and response to Kava, and to explore the effects of Kava on the expression of specific genes. Consenting participants will be randomly allocated to take either Kava or placebo over 18 weeks. They will be assessed at regular interviews throughout the trial and will have four blood tests (liver function tests to monitor participant safety, and collection of genetic material providing information on neurochemistry). The design of the study is a multi-centre, 18-week, 2-arm, double-blind randomised clinical trial (RCT) using a standardised pharmaceutical-grade water-soluble extract of Kava (240mg of kavalactones per day) versus placebo in 210 adults with GAD.
Interventions
DIETARY_SUPPLEMENTKava (240mg of kavalactones per day)
Kava 60 milligrams per tablet = 240mg of kavalactones per day
DIETARY_SUPPLEMENTPlacebo
Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.
Sponsors
Swinburne University of Technology
The University of Queensland
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
To be considered for inclusion in this study, participants will be required to meet the following criteria: * Aged between 18-70 years * Meets the Diagnostic and Statistical Manual (DSM) IV and DSM-V diagnostic criteria for generalised anxiety disorder (GAD) based on structured interview (Mini International Neuropsychiatric Interview-Plus 6 \[MINI-Plus 6\]. Note that while the MINI-Plus 6 uses the DSM-IV criteria, the same criteria are used in the DSM-V). * Presents with anxiety (Hamilton Anxiety Rating Scale ≥ 18) at the time of study entry * Fluent in written and spoken English * Provides a signed copy of the consent form Participants are ineligible to enter the trial if they have any of the following conditions: * Primary diagnosis other than GAD * Presentation of moderate to severe depressive symptoms (Montgomery-Asberg Rating Scale: MADRS ≥ 18 at time of study entry or ≥ 24 at any time during study) * Presentation of suicidal ideation (≥ 3 on MADRS suicidal thoughts domain at time of study entry or at any time during study) * Current diagnosis of bipolar disorder or schizophrenia on structured interview (MINI Plus) * Current substance/alcohol use disorder on structured interview (MINI Plus) Page 21 of 39 Commercial-in-Confidence * Currently taking an antidepressant, mood stabiliser, antipsychotic, anticonvulsant, warfarin or thyroxin, or current regular use (more than 2 days per week) of a benzodiazepine or opioid-based analgesic * Current use of a psychotropic nutraceutical (e.g. St John's wort) * Previous intolerance to kava * Three or more failed trials of pharmacotherapy for the current GAD episode * Recently commenced psychotherapy (within four weeks of study entry) * Known or suspected clinically unstable systemic medical disorder * Diagnosed hepato-biliary disease/inflammation * Elevated liver enzymes at baseline blood test * Pregnancy or breastfeeding, or trying to conceive * Not using medically approved contraception (including abstinence) if female and of childbearing age * Unable to participate in all scheduled visits, treatment plan, or other trial procedures according to the protocol (except for the optional genetic component)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAMA) - change in score | 18 weeks | Reduction of participant's anxiety will be assessed on the HAMA from baseline to week 16 across time used a mixed methods model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention | 18 weeks | Will assess whether response to Kava will be moderated by gamma-aminobutyric acid (GABA) transporter polymorphisms. Specifically, whether rs2601126-T allele or rs2697153-A allele carriers have greater reduction of anxiety |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in score to psychometric questionnaire measures | 18 weeks | Depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS), self-rated anxiety on the Beck Anxiety Inventory (BAI), pathological worry on the Penn State Worry Questionnaire (PSWQ), and health-related quality of life on the Short Form Survey-12 (SF-12) will also be significantly improved by Kava over placebo; and |
| Monoamine and GABA differential gene expression | 8 weeks | Differential gene expression will be assessed from baseline to week 8 from participants in the Melbourne site. This will determine whether Kava increases expression of genes effecting expression of neurochemical e.g. GABA, and monoamines |
Countries
Australia
Outcome results
None listed