Pharmacokinetics
Conditions
Keywords
kava, dietary supplement, anxiety, generalized anxiety disorder (GAD)
Brief summary
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
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.
Interventions
Participants will be given three 75mg kava capsules per day for one week
DRUGPlacebo
Participants will be given three placebo capsules per day for one week
Sponsors
Thorne HealthTech, Inc
National Center for Complementary and Integrative Health (NCCIH)
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults ages 18-50 who meet Diagnostic Statistical Manual (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 Obsessive Compulsive Disorder * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean PRKACA Change | From Baseline (pre dose) to 1 week after taking the first dose (post dose) | The change in mean PRKACA value from pre to post-treatment |
Countries
United States
Participant flow
Recruitment details
Individuals were recruited from flyers that were distributed in and around the Gainesville area and from the University of Florida (UF) Psychiatry and Psychology clinics.
Pre-assignment details
Individuals were excluded it the met any of the exclusion criteria at screening or baseline.
Participants by arm
| Arm | Count |
|---|---|
| Kava Pharmacokinetics Group 75 mg kava dietary supplement capsules per day for one week.
Kava Dietary Supplement: Participants will be given three 75mg kava capsules per day for one week | 10 |
| Placebo Three placebo capsule per day for one week
Placebo: Participants will be given three placebo capsules per day for one week | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Kava Pharmacokinetics Group | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 26 years | 23 years | 25 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 16 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 4 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Mean PRKACA Change
The change in mean PRKACA value from pre to post-treatment
Time frame: From Baseline (pre dose) to 1 week after taking the first dose (post dose)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Kava Pharmacokinetics Group | Mean PRKACA Change | Pre dose PRKACA | 7224.56 relative fluorescence units | Standard Deviation 3526.22 |
| Kava Pharmacokinetics Group | Mean PRKACA Change | Post dose PRKACA | 6307.21 relative fluorescence units | Standard Deviation 5887.36 |
| Placebo | Mean PRKACA Change | Pre dose PRKACA | 5348.93 relative fluorescence units | Standard Deviation 2027.02 |
| Placebo | Mean PRKACA Change | Post dose PRKACA | 6495.7 relative fluorescence units | Standard Deviation 3757.65 |