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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00662259
Recruitment Status : Unknown
Verified May 2009 by University of California, San Diego.
Recruitment status was:  Recruiting
First Posted : April 21, 2008
Last Update Posted : May 22, 2009
Hoffmann-La Roche
Information provided by:
University of California, San Diego

April 17, 2008
April 21, 2008
May 22, 2009
April 2008
December 2009   (Final data collection date for primary outcome measure)
To evaluate the effect of an anxiolytic drug versus placebo on brain activity at rest and during emotional stimuli using fMRI. [ Time Frame: 7 weeks ]
Same as current
Complete list of historical versions of study NCT00662259 on Archive Site
  • To evaluate the effects of an anxiolytic drug versus placebo on eye blink startle response at rest and during emotional stimuli (anxiety potentiated startle, APS) as well as on clinical scales. [ Time Frame: 7 weeks ]
  • To correlate the fMRI measurements with the clinical/behavioral measurements of efficacy. [ Time Frame: 7 weeks ]
Same as current
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Drug Treatment Validation of Functional Magnetic Resonance Imaging in Generalized Anxiety Disorder
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
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.
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.
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Generalized Anxiety Disorder
  • Drug: Alprazolam (Xanax)
    Drug dose will be fixed across patients: alprazolam 0.5 mg b.i.d escalating to 1.0 mg b.i.d. The treatment duration will be approximately 28 days (4 weeks).
    Other Name: Xanax
  • Drug: Placebo
    Placebo, bid, p.o. for 28 +/- 2 days.
  • Experimental: alprazolam
    Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder.
    Intervention: Drug: Alprazolam (Xanax)
  • Placebo Comparator: placebo
    A placebo comparator will be administered to 12 patients with generalized anxiety disorder
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
Same as current
December 2009
December 2009   (Final data collection date for primary outcome measure)

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 ECG), especially no findings (including concomitant medications) that would constitute contraindications for treatment with alprazolam
  3. DSM-IV criteria for GAD (exception: at least 3 months of symptoms)
  4. HAM-A at screening >/= 20
  5. 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 FSH level greater than 40 mIU/mL unless the subject is receiving HRT), 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. BMI > 32.5 kg/m2
  14. Contraindication to magnetic resonance imaging based on a standard fMRI screening forms
  15. Concurrent participation in an 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®)
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Martin P. Paulus, MD, University of California San Diego, Department of Psychiatry
University of California, San Diego
Hoffmann-La Roche
Principal Investigator: Martin P Paulus, MD University of California, San Diego
University of California, San Diego
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP