Trial Review

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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
Date results information 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] 251691 0
None
Universal Trial Number (UTN)
Trial acronym
KALM Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety 257283 0
Mood 257284 0
Condition category
Condition code
Mental Health 257430 257430 0 0
Anxiety
Alternative and Complementary Medicine 257431 257431 0 0
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] 256420 0
Treatment: Drugs
Comparator / control treatment
As mentioned above one group will receive placebo tablets throughout the study.
Control group
Placebo

Outcomes
Primary outcome [1] 258351 0
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] 258351 0
Data collection will occur during week 0 at baseline and at weeks 1,2,4,7,8.
Primary outcome [2] 258352 0
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] 258352 0
Data collection will occur during week 0 at baseline and at weeks 1,2,4,7,8.
Secondary outcome [1] 264087 0
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] 264087 0
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?
No
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
75
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 256906 0
Commercial sector/Industry
Name [1] 256906 0
Integria
Country [1] 256906 0
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] 256178 0
None
Name [1] 256178 0
Address [1] 256178 0
Country [1] 256178 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258916 0
The Melbourne Clinic Research Ethics Committee
Ethics committee address [1] 258916 0
130 Church Street
RICHMOND VIC 3121
Ethics committee country [1] 258916 0
Australia
Date submitted for ethics approval [1] 258916 0
01/01/2010
Approval date [1] 258916 0
11/03/2010
Ethics approval number [1] 258916 0
182
Ethics committee name [2] 267106 0
Human Research Ethics Committee, Swinburne University.
Ethics committee address [2] 267106 0
Level 7, 60 William Street
Hawthorn Campus
swinburne University
Ethics committee country [2] 267106 0
Australia
Date submitted for ethics approval [2] 267106 0
Approval date [2] 267106 0
15/01/2011
Ethics approval number [2] 267106 0
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 31122 0
Address 31122 0
Country 31122 0
Phone 31122 0
Fax 31122 0
Email 31122 0
Contact person for public queries
Name 14369 0
Jerome Sarris
Address 14369 0
The Melbourne Clinic

130 Church St, Richmond

Victoria, 3121
Country 14369 0
Australia
Phone 14369 0
+613 9420 9350
Fax 14369 0
Email 14369 0
[email protected]
Contact person for scientific queries
Name 5297 0
Jerome Sarris
Address 5297 0
The Melbourne Clinic

130 Church St, Richmond

Victoria, 3121
Country 5297 0
Australia
Phone 5297 0
+613 9420 9350
Fax 5297 0
Email 5297 0
[email protected]

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.