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

• ClinicalTrials.gov Identifier: NCT02219880
• Recruitment Status: Completed
• First Posted: August 19, 2014
• Last Update Posted: October 15, 2018
• Sponsor: University of Melbourne
• Collaborators: Swinburne University of Technology; The University of Queensland
• Information provided by (Responsible Party): Jerome Sarris, University of Melbourne

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 (Clinical Trial)
• 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: October 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

Outcome Measures

Primary Outcome Measures :

1. Hamilton Anxiety Rating Scale (HAMA) - change in score [ Time Frame: 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 :

1. Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention [ Time Frame: 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:

1. Changes in score to psychometric questionnaire measures [ Time Frame: 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
2. Monoamine and GABA differential gene expression [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Australia, Queensland

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia, 4006

Australia, Victoria

Centre for Human Psychopharmacology - Swinburne University

Melbourne, Victoria, Australia, 3122

Sponsors and Collaborators

University of Melbourne

Swinburne University of Technology

The University of Queensland

Investigators

• Principal Investigator: Jerome Sarris, PhD; The University of Melbourne and The Melbourne Clinic

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Savage KM, Stough CK, Byrne GJ, Scholey A, Bousman C, Murphy J, Macdonald P, Suo C, Hughes M, Thomas S, Teschke R, Xing C, Sarris J. Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial. Trials. 2015 Nov 2;16:493. doi: 10.1186/s13063-015-0986-5.

• Responsible Party: Jerome Sarris, Dr Jerome Sarris, University of Melbourne
• ClinicalTrials.gov Identifier: NCT02219880
• Other Study ID Numbers: 137/14
• First Posted: August 19, 2014
• Last Update Posted: October 15, 2018
• Last Verified: October 2018

Keywords provided by Jerome Sarris, University of Melbourne:

Kava; Anxiety; Generalized Anxiety Disorder; Psychiatric; Anxiolytic; GABA; Kavalactones

Additional relevant MeSH terms:

Disease; Anxiety Disorders; Pathologic Processes; Mental Disorders