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

Primary Purpose

Generalized Anxiety Disorder

Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Kava (240mg of kavalactones per day)
Placebo
Sponsored by
University of Melbourne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Generalized Anxiety Disorder focused on measuring Kava, Anxiety, Generalized Anxiety Disorder, Psychiatric, Anxiolytic, GABA, Kavalactones

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Royal Brisbane & Women's Hospital
  • Centre for Human Psychopharmacology - Swinburne University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Kava - standardised 240mg kavalactones

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
August 13, 2014
Last Updated
October 10, 2018
Sponsor
University of Melbourne
Collaborators
Swinburne University of Technology, The University of Queensland
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1. Study Identification

Unique Protocol Identification Number
NCT02219880
Brief Title
Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial
Acronym
KGAD
Official Title
Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 13, 2015 (Actual)
Primary Completion Date
May 31, 2018 (Actual)
Study Completion Date
May 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Melbourne
Collaborators
Swinburne University of Technology, The University of Queensland

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Anxiety Disorder
Keywords
Kava, Anxiety, Generalized Anxiety Disorder, Psychiatric, Anxiolytic, GABA, Kavalactones

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Kava - standardised 240mg kavalactones
Arm Type
Experimental
Arm Description
Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day
Intervention Type
Dietary Supplement
Intervention Name(s)
Kava (240mg of kavalactones per day)
Other Intervention Name(s)
Kava, Kavalactones, Piper methysticum
Intervention Description
Kava 60 milligrams per tablet = 240mg of kavalactones per day
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.
Primary Outcome Measure Information:
Title
Hamilton Anxiety Rating Scale (HAMA) - change in score
Description
Reduction of participant's anxiety will be assessed on the HAMA from baseline to week 16 across time used a mixed methods model.
Time Frame
18 weeks
Secondary Outcome Measure Information:
Title
Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention
Description
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
Time Frame
18 weeks
Other Pre-specified Outcome Measures:
Title
Changes in score to psychometric questionnaire measures
Description
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
Time Frame
18 weeks
Title
Monoamine and GABA differential gene expression
Description
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
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerome Sarris, PhD
Organizational Affiliation
The University of Melbourne and The Melbourne Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Brisbane & Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
Facility Name
Centre for Human Psychopharmacology - Swinburne University
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3122
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
31813230
Citation
Sarris J, Byrne GJ, Bousman CA, Cribb L, Savage KM, Holmes O, Murphy J, Macdonald P, Short A, Nazareth S, Jennings E, Thomas SR, Ogden E, Chamoli S, Scholey A, Stough C. Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study. Aust N Z J Psychiatry. 2020 Mar;54(3):288-297. doi: 10.1177/0004867419891246. Epub 2019 Dec 8.
Results Reference
derived
PubMed Identifier
26527536
Citation
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.
Results Reference
derived

Learn more about this trial

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

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