ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12610000381088

Ethics application status

Approved

Date submitted

4/05/2010

Date registered

12/05/2010

Date last updated

19/11/2018

Date data sharing statement initially provided

19/11/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

The Kava & Anxiety Lowering Medication (KALM) study

Scientific title

Examining the effects of administration of Kava on anxiety versus placebo in adults aged 18-65 presenting with Generalized Anxiety Disorder (GAD).

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

KALM Study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Anxiety

Mood

Condition category

Condition code

Mental Health

Anxiety

Alternative and Complementary Medicine

Other alternative and complementary medicine

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Each participant will be required to consume 1 dose of Kava tablets (120mg of kavalactones) or 1 dose of Placebo tablets. The placebo tablets are made from microcellulose and are identical in taste and appearance to their active counterpart.

Interventions used for the first 3 weeks of the controlled phase of the trial: Group 1) 1 Kava tablet prescribed twice per day (standardised for 120 mg of kavalactones per day: active constituent); Group 2) 1 placebo tablet twice per day.
Before randomisation occurs, a one week placebo run-in will be employed, with any responders having a >50% reduction on the Hamilton Anxiety Scale (HAM-A) to be excluded.

After 3 weeks of the controlled phase, non-responders will be given an extra tablet (a doubling of the dose- either double placebo or 240mg of Kava: still within TGA recommended dosage range). All participants will be switched to placebo during Week 8 to observe any occurrence of rebound anxiety or withdrawal symptoms.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

As mentioned above one group will receive placebo tablets throughout the study.

Control group

Placebo

Outcomes

Primary outcome [1]

Evaluate the efficacy and safety of Kava monotherapy compared to Placebo in General Anxiety Disorder (GAD).

This will be assessed by (a)Structured Clinical Interview for Diagnostic and Stastical Manual for mental Disorders (DSM) disorders (automated version) b) Hamiton Anxiety Scale (HAM-A) (primary outcome) c) Montgomery-Asberg Depression Rating Scale (MADRS) d) Weekly safety checklists (for adverse reactions) e) The Arizona Sexual Experience Scale (ASEX) to assess the difference in sexual dysfunction between placebo and Kava. f) Addiction assessment scale to observe whether any perceived addictiveness to the intervention is occurring g) Three blood tests (liver function test and a genetic test providing information on liver enzyme function and neurochemistry).

Timepoint [1]

Data collection will occur during week 0 at baseline and at weeks 1,2,4,7,8.

Primary outcome [2]

Compare Kava at 240mg and 120mg of kavalactones to determine any differences in efficacy.

This will be assessed by (a)Structured Clinical Interview for DSM disorders (automated version) b) HAM-A (primary outcome) c) MADRS d) Weekly safety checklists (for adverse reactions) e) The Arizona Sexual Experience Scale (ASEX) to assess the difference in sexual dysfunction between paroxetine, placebo, and Kava. f) Addiction assessment scale to observe whether any perceived addictiveness to the interventions is occurring g) Three blood tests (liver function test and a genetic test providing information on liver enzyme function and neurochemistry).

Timepoint [2]

Data collection will occur during week 0 at baseline and at weeks 1,2,4,7,8.

Secondary outcome [1]

Assess any differences between responders or non-responders to Kava due to genetic differences (liver enzyme or neurochemical polymorphisms).

Genetic tests exploring polymorphisms of liver enzyme DNA (cytochrome P450 2D6 and 3A4, and brain chemical DNA (GABA receptors and transporters, noradrenaline and serotonin transporters, Val158Met) holds the potential to determine genetic profiles of responders and non-responders.

Timepoint [1]

Data collection will occur during week 0 at baseline and at weeks 1 and 7.

Eligibility

Key inclusion criteria

Any person aged 18-65 presenting with a structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Structured Clinical Interview for DSM (SCID) diagnosed GAD, and a HAM-A of >14.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Primary diagnosis other than GAD; Psychotic or Bipolar illness; Significant suicidal ideation in the previous 6 months; antidepressant, mood stabiliser, antipsychotic, opiod analgesics, St John’s wort, Human immunodeficiency virus (HIV), anti-tumoral/cancer, blood pressure, warfarin, Parkinson’s, epileptic, migraine or anti-ulcer medication; Diagnosed hepato-biliary disease/inflammation (or elevated liver enzymes at Baseline blood test); Thyroid disease (or thyroid hormone abnormality at baseline blood test); DSM-IV diagnosed substance abuse or dependency disorder including alcohol in the previous 6 months; Regular use of Kava in the previous 12 months; Previous adverse reaction to Kava; Seeing a psychologist or counsellor currently or in the previous month; Pregnancy or trying to conceive; Lack of facility in written or spoken English; Montgomery-Asberg Depression Rating Scale (MADRS) score of >18.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Participants will be contacted via avertisements in health clinics and on community notice boards. Participants will be screened to ensure they pass the inclusion/exclusion criteria and allocated a participant number and treatment condition. The person who determines if a participant is eleigible for participation will be unaware, when the decision is made, to which group the participant will be allocated to. Allocation concealment was performed using numbered containers.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

A disinterested third party generated the randomisation list using a computerised random number sequence generator. Participants were allocated to receive 1 of 2 treatments. Allocation involved contacting the holder of the allocation schedule who is off-site.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Participants who are non-responders in the first 3 weeks of treatment will have their number of tablets taken per day doubled.

Phase

Phase 3 / Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/03/2011

Actual

12/04/2011

Date of last participant enrolment

Anticipated

Actual

20/12/2011

Date of last data collection

Anticipated

Actual

22/02/2012

Sample size

Target

160

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Integria

Address [1]

Level 1, 8
Clunies Ross Court, Eight Mile Plains Qld 4300

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Integria

Address

Level 1, 8
Clunies Ross Court, Eight Mile Plains Qld 4300

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Melbourne Clinic Research Ethics Committee

Ethics committee address [1]

130 Church Street
RICHMOND VIC 3121

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/01/2010

Approval date [1]

11/03/2010

Ethics approval number [1]

182

Ethics committee name [2]

Human Research Ethics Committee, Swinburne University.

Ethics committee address [2]

Level 7, 60 William Street
Hawthorn Campus
swinburne University

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

15/01/2011

Ethics approval number [2]

2010/254

Summary

Brief summary

The design of the study is a phase IV, 2-arm, 8-week, randomised, double-blind, placebo-controlled trial using one 3.2 gram tablet of Kava (Piper methysticum),
twice per day equal to 120mg of kavalactones (but in non-responders at week 3 this will be doubled to two tablets twice per day equal to 240mg of kavalactones),
or matching placebo, in 100 currently anxious participants with diagnosed generalised anxiety disorder (GAD).
Participants are required to fill out assessment forms throughout the study and to have 3 blood tests (liver function tests and a genetic test providing information on liver enzyme function and neurochemistry).
Assessment will occur at Healthscope hospital sites in Victoria and at Swinburne University of Technology, Hawthorn VIC.
Data collection will occur during week 0 at baseline and at weeks 1,2,4,7,8 by trained research assistants. Assessment tools used: Compulsory a) Structured Clinical Interview for DSM disorders (automated version) b) HAM-A (primary outcome) c) MADRS d) Weekly safety checklists (for adverse reactions) e) Current health & medications questionnaire to assess their current health and any medications they are currently taking f) Drug Check to assess alcohol and other drug use g) Demographics questionnaire to assess age, education, marital status, employment h) The Arizona Sexual Experience Scale (ASEX) to assess the difference in sexual dysfunction between paroxetine, placebo, and Kava. i) Addiction assessment scale to observe whether any perceived addictiveness to the interventions is occurring j) Three blood tests (liver function test and a genetic test providing information on liver enzyme function and neurochemistry).   
Participants will be required to attend 6 visits at the Brain Science Institute,  Hawthorn. The first visit is a baseline session. Participants will be asked to complete all tests: screening assessments, consent forms, mood and anxiety questionnaires. Testing for all subsequent visits will follow the same outline of their baseline session (excluding consent forms and including an adverse effects safety questionnaire). Participants will be given $100 each at the completion of the study to compensate for their time and to cover travel expenses if required.  The recruitment, data collection and analysis period will be approximately 1 year.
Data will be analysed by research team using SPSS 17.0. Repeated measures ANOVAs will be used to assess any changes between groups across time.

Trial website

TBA

Trial related presentations / publications

None

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Jerome Sarris

Address

The Melbourne Clinic

130 Church St, Richmond

Victoria, 3121

Country

Australia

Phone

+613 9420 9350

Fax

jsarris@unimelb.edu.au

Contact person for scientific queries

Name

Jerome Sarris

Address

The Melbourne Clinic

130 Church St, Richmond

Victoria, 3121

Country

Australia

Phone

+613 9420 9350

Fax

jsarris@unimelb.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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