Randomized, Double-blind, Placebo-controlled Study of a Benzodiazepine vs Placebo on Functional Magnetic Resonance Imaging (fMRI) of the Brain, and on Behavioral/Clinical Measures in Patients With Generalized Anxiety Disorder
Overview
- Phase
- Phase 4
- Intervention
- Alprazolam (Xanax)
- Conditions
- Generalized Anxiety Disorder
- Sponsor
- University of California, San Diego
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Signal Change in Brain Activity in the Amygdala When Viewing Emotional Faces
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to find out how an anti-anxiety drug or placebo affects the activity of your brain when you are at rest and when you are viewing emotional material, such as, emotional faces and pictures.
Detailed Description
This is an exploratory study to evaluate the usefulness of fMRI as a biomarker to measure the response to a known, FDA approved marketed anxiolytic. As such, this is not a study testing safety and efficacy of an approved medicine; it is a study to evaluate the usefulness of fMRI (a non-significant risk device procedure) to correlate the clinical/behavioral effects of a marketed anxiolytic with brain activity assessed by magnetic resonance imaging. fMRI is a more direct measure of brain function than behavior, outcomes are quantitative and objective. As such, it may be more specific, i.e., may be more sensitive to drug effects or show them earlier than clinical endpoints and enable determination of efficacy in smaller or shorter studies than those required to show effects on clinical endpoints. Finally, imaging may allow differentiation of placebo responders from true drug responders.
Investigators
Gregory G. Brown
Professor
University of California, San Diego
Eligibility Criteria
Inclusion Criteria
- •Male or female between 18 - 65 years of age, inclusive
- •In good general health (as determined by medical history, physical examination, laboratory assessments and electrocardiogram (ECG)), especially no findings (including concomitant medications) that would constitute contraindications for treatment with alprazolam
- •Diagnostic and Statistical Manual-IV criteria for Generalized Anxiety Disorder (GAD) (exception: at least 3 months of symptoms)
- •Hamilton Anxiety Scale at screening \>/= 20
- •Montgomery-Asberg Depression Rating Scale (MADRS) at screening \< 25
- •Prior medications washout:
- •2-week medication washout prior to randomization for most psychotropic medications
- •If prior history of fluoxetine use, this drug must have been discontinued at least 5 weeks before randomization
- •For females of non-childbearing potential: either postmenopausal for the past year (confirmed by an follicle stimulating hormone level greater than 40 mIU/mL unless the subject is receiving hormone replacement therapy), or surgically sterile (e.g., tubal ligation, hysterectomy)
- •Males and female subjects of child-bearing potential may be included if using appropriate contraceptive methods:
Exclusion Criteria
- •Axis I disorder other than stated above with the exception of the following permitted comorbidities:
- •history of (within past 6 months) or current dysthymia
- •current (within past 6 months) depressive episode with MADRS at baseline \< 25
- •history of major depression as long as no current depressive episode as defined above
- •Drug or alcohol dependence in the past 6 months
- •Positive urine toxicology (drugs of abuse as determined by clinician's assessment of positive urine test)
- •Active suicidal ideation (determined by clinician)
- •For females of childbearing potential: Pregnancy or intent to become pregnant or currently breastfeeding
- •Current use of beta-blockers or stimulants (e.g., Methylphenidate, d-Amphetamine, modafinil, and illicit drugs like cocaine or 3,4-methylenedioxy-N-methylamphetamine \[MDMA\])
- •Current regular use of antihistamines (except for inhalants which are permitted)
Arms & Interventions
alprazolam
Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder.
Intervention: Alprazolam (Xanax)
placebo
A placebo comparator will be administered to 12 patients with generalized anxiety disorder
Intervention: Placebo
Outcomes
Primary Outcomes
Signal Change in Brain Activity in the Amygdala When Viewing Emotional Faces
Time Frame: 0,1,28 days
Extent of activation a brain signal when matching emotional face expressions as a percentage of the brain signal when matching geometric designs. The brain signal is the blood oxygen level dependent signal measured by functional magnetic resonance imaging.
Signal Change in Brain Activity in the Insula When Anticipating the Viewing of Emotional Pictures.
Time Frame: 0,1,28 days
Extent of activation of a brain signal when anticipating the viewing of an emotional picture as a percentage of brain signal when the viewing of an emotional signal is not anticipated. The brain signal is the blood oxygen level dependent signal as measured by functional magnetic resonance imaging.
Secondary Outcomes
- Score on the Hamilton Anxiety Scale(0, 7, 28 days)
- Score on the Penn State Worry Scale(0, 7, 28 days)