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

Generalized Anxiety Disorder Clinical Trial

— KGAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02219880
• Other study ID #: 137/14
• Status: Completed
• Phase: Phase 4
• Start date: October 13, 2015
• Est. completion date: May 31, 2018

Study information

• Verified date: October 2018
• Source: University of Melbourne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: May 31, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Anxiety Disorders
• Disease
• Generalized Anxiety Disorder

Intervention

Dietary Supplement:
• Kava (240mg of kavalactones per day)
Kava 60 milligrams per tablet = 240mg of kavalactones per day
• Placebo
Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.

Locations

Country	Name	City	State
Australia	Royal Brisbane & Women's Hospital	Brisbane	Queensland
Australia	Centre for Human Psychopharmacology - Swinburne University	Melbourne	Victoria

Sponsors (3)

Lead Sponsor	Collaborator
University of Melbourne	Swinburne University of Technology, The University of Queensland

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in score to psychometric questionnaire measures	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	18 weeks
Other	Monoamine and GABA differential gene expression	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	8 weeks
Primary	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	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