Biomarker Changes and Anxiolytic Effects-Phase 2

Study Overview
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Brief Summary
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This study will examine the utility of plasma and urinary based biomarkers for the anxiolytic properties of kava. The investigators will conduct a one week, double blind, randomized placebo controlled trial of kava, dosed at three 75 mg capsules per day, vs placebo, in adults with generalized anxiety disorder.

Detailed Description
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This study will examine the utility of plasma and urinary based biomarkers for the anxiolytic properties of kava, a natural dietary supplement. The investigators will conduct a one week, double blind, randomized placebo controlled trial of kava, dosed at three 75 mg capsules per day, vs placebo, in adults with generalized anxiety disorder. Clinical measures of anxiety, blood, and urine will be obtained. Biomarkers of interest include PRKACA, cortisol, urinary TCE, and NA5HT. Participants will be assessed pre- and post-treatment. The participants will also be followed for 12 weeks after the end of treatment to identify any potential rare adverse events, particularly liver toxicity, that appear in a delayed fashion.

Official Title
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A Phased Clinical Trial of a Dietary Supplement Kava: Biomarker Changes and Anxiolytic Effects Phase 2: Kava Biomarker

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: Kava Dietary Supplement
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ages 18-50 who meet DSM-5 criteria for GAD as the primary psychiatric diagnosis No more than one failed therapeutic trial of an FDA approved medication for the treatment of GAD Score of>14 on the Hamilton Anxiety Rating Scale at both screening and baseline At least a 4 (moderate) on the Clinical Global Impressions Severity Scale at both screening and baseline Females of potential childbearing status must use adequate contraceptive precautions. Exclusion Criteria: Unwilling/unable/unsafe to stop psychotropic medications (if on any) for the duration of the study Inability to refrain from acetaminophen, alcohol or other potentially hepatotoxic substances History of liver disease or current liver disease or clinically significant elevation in serum liver chemistries Unstable medical or neurological condition Positive urine drug screen for substances of abuse Active substance abuse/dependence Lifetime history of a psychotic disorder, bipolar disorder, PTSD or OCD Any significant risk for self-harm or suicidality as determined by the principal investigator or suicide attempt within the last 6 months Psychotherapy newly instituted during the 6 weeks leading up to enrollment in the study. Subjects established in psychotherapy without change during the course of the study may participate Montgomery-Asberg Depression Rating Scale (MADRS) > 17 (moderate or severe depressive symptoms)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kava Pharmacokinetics Group<br>75 mg kava dietary supplement capsules per day for one week. | Drug: Kava Dietary Supplement<br>* Participants will be given three 75mg kava capsules per day for one week<br>|
| Placebo Comparator: Placebo<br>Three placebo capsule per day for one week | Drug: Placebo<br>* Participants will be given three placebo capsules per day for one week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean PRKACA change to validate PRKACA change % | To measure the mean PRKACA change to validate PRKACA change % of biomarkers | From Baseline up to Study Completion Date, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kava, dietary supplement, anxiety, generalized anxiety disorder (GAD)