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

Sponsor

University of Melbourne (Other)

Overall Status

Completed

CT.gov ID

NCT02219880

Collaborator

Swinburne University of Technology (Other), The University of Queensland (Other)

178

Enrollment

Locations

Arms

31.6

Actual Duration (Months)

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Generalized Anxiety Disorder	Dietary Supplement: Kava (240mg of kavalactones per day) Dietary Supplement: Placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

178 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 13, 2015

Actual Primary Completion Date :

May 31, 2018

Actual Study Completion Date :

May 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 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 Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.
Experimental: Kava - standardised 240mg kavalactones Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day	Dietary Supplement: Kava (240mg of kavalactones per day) Kava 60 milligrams per tablet = 240mg of kavalactones per day Other Names: Kava Kavalactones Piper methysticum

Arm

Intervention/Treatment

Placebo Comparator: Placebo

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

Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.

Experimental: Kava - standardised 240mg kavalactones

Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day

Dietary Supplement: Kava (240mg of kavalactones per day)

Kava 60 milligrams per tablet = 240mg of kavalactones per day

Other Names:

Kava

Kavalactones

Piper methysticum

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Brisbane & Women's Hospital	Brisbane	Queensland	Australia	4006
2	Centre for Human Psychopharmacology - Swinburne University	Melbourne	Victoria	Australia	3122