Drug Treatment Validation of Functional Magnetic Resonance Imaging in Generalized Anxiety Disorder

Phase 4

Completed

• Conditions: Generalized Anxiety Disorder
• Interventions: Drug: Alprazolam (Xanax); Drug: Placebo

• Registration Number: NCT00662259
• Lead Sponsor: University of California, San Diego

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.

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-17
• Study First Submitted QC: 2008-04-18
• Study First Posted: 2008-04-21
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Results First Submitted: 2019-05-23
• Status Verified: 2019-06
• Results First Submitted QC: 2019-06-28
• Last Update Submitted: 2019-06-28
• Results First Posted: 2019-07-25
• Last Update Posted: 2019-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Male or female between 18 - 65 years of age, inclusive

2. 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

3. Diagnostic and Statistical Manual-IV criteria for Generalized Anxiety Disorder (GAD) (exception: at least 3 months of symptoms)

4. Hamilton Anxiety Scale at screening >/= 20

5. Montgomery-Asberg Depression Rating Scale (MADRS) at screening < 25

6. 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

7. 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)

8. Males and female subjects of child-bearing potential may be included if using appropriate contraceptive methods:

   • must use abstinence or two methods of contraception throughout the trial:

     • should include one primary (e.g., systemic hormonal contraception, vasectomy of the male partner) AND one secondary barrier method (e.g., latex condoms, spermicide) OR
     • a double barrier method (e.g., latex condom plus spermicide (foam, suppository, gel, cream)) may be used

9. GAD should be the clinically predominant disorder, as judged by the investigator, considering relative severity and impact on functioning

Exclusion Criteria

1. 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

2. Drug or alcohol dependence in the past 6 months

3. Positive urine toxicology (drugs of abuse as determined by clinician's assessment of positive urine test)

4. Active suicidal ideation (determined by clinician)

5. For females of childbearing potential: Pregnancy or intent to become pregnant or currently breastfeeding

6. 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])

7. Current regular use of antihistamines (except for inhalants which are permitted)

8. Current use of herbal medication for mood or anxiety disorders and unwillingness to discontinue use for the duration of the study

9. Current use of fluoxetine

10. Concomitant psychotropic medications including regular use of sleeping medications (also herbals)

    • occasional use of sleeping medication, with the exception of benzodiazepines, is permitted as long as it is not taken the evening prior to a visit

11. Past intolerance (including allergic) to, or clear history of non-response to the study medication

12. Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400 mg/d (approximately 4 cups of coffee or equivalent)

13. Body mass index > 32.5 kg/m2

14. Contraindication to magnetic resonance imaging based on a standard fMRI screening forms

15. Concurrent participation in an institutional review board (IRB) approved investigational drug trial

16. Any other reason why, per clinician, the patient should not participate in this study (to be included in this assessment are all considerations, warnings, precautions as per current FDA-approved drug label for Xanax®)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
alprazolam	Alprazolam (Xanax)	Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder.
placebo	Placebo	A placebo comparator will be administered to 12 patients with generalized anxiety disorder

Primary Outcome Measures

Name	Time	Method
Signal Change in Brain Activity in the Amygdala When Viewing Emotional Faces	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.	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 Outcome Measures

Name	Time	Method
Score on the Hamilton Anxiety Scale	0, 7, 28 days	Measured participant's general anxiety; range 0 - 56; higher scores worse
Score on the Penn State Worry Scale	0, 7, 28 days	Measured participant's extent of worry; range 16 - 80, higher scores worse

Trial Locations

Locations (1)

University of California, San Diego; 🇺🇸 San Diego, California, United States