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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by University of California, San Diego.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00662259
First received: April 17, 2008
Last updated: May 21, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Generalized Anxiety Disorder
Drug: Alprazolam (Xanax)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • To correlate the fMRI measurements with the clinical/behavioral measurements of efficacy. [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2008
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alprazolam
Alprazolam, an FDA-approved drug, will be administered to 24 patients with 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
Placebo Comparator: placebo
A placebo comparator will be administered to 12 patients with generalized anxiety disorder
Drug: Placebo
Placebo, bid, p.o. for 28 +/- 2 days.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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®)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00662259

Contacts
Contact: Elena Kosheleva 858-405-6677 anxietystudy@ucsd.edu

Locations
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92093
Contact: Christina Wierenga, PhD    858-405-6677      
Sub-Investigator: Gregory Brown, PhD         
Sponsors and Collaborators
University of California, San Diego
Hoffmann-La Roche
Investigators
Principal Investigator: Martin P Paulus, MD University of California, San Diego
  More Information

Publications:
Responsible Party: Martin P. Paulus, MD, University of California San Diego, Department of Psychiatry
ClinicalTrials.gov Identifier: NCT00662259     History of Changes
Other Study ID Numbers: WP21030
Study First Received: April 17, 2008
Last Updated: May 21, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
Anxiety disorders
Generalized anxiety

Additional relevant MeSH terms:
Anxiety Disorders
Mental Disorders
Alprazolam
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014