Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial

Study Overview
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Brief Summary
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The use of Kava in Generalised Anxiety Disorder: an 18-week double-blind, randomised, placebo-controlled study.

Detailed Description
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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.

Official Title
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Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Dietary Supplement: Kava (240mg of kavalactones per day)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Inert tablets matched for colour, size and consistency to active arm treatment. Both treatment arm tablets will match in appearance, and neither participants nor the trial clinicians will know what they are taking. | Dietary Supplement: Placebo<br>* Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.<br>|
| Experimental: Kava - standardised 240mg kavalactones<br>Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day | Dietary Supplement: Kava (240mg of kavalactones per day)<br>* Kava 60 milligrams per tablet = 240mg of kavalactones per day<br>* Other names: Piper methysticum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Anxiety Rating Scale (HAMA) - change in score | Reduction of participant's anxiety will be assessed on the HAMA from baseline to week 16 across time used a mixed methods model. | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention | 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 | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kava, Anxiety, Generalized Anxiety Disorder, Psychiatric, Anxiolytic, GABA, Kavalactones