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

NCT00662259 | Completed Phase 4 Results

• 1 other identifier: WP21030
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Generalized Anxiety Disorder

Keywords

Anxiety disorders; Generalized anxiety

Outcome Measures

Primary Outcomes (2)

• Signal Change in Brain Activity in the Amygdala When Viewing Emotional Faces

  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.

  0,1,28 days

• Signal Change in Brain Activity in the Insula When Anticipating the Viewing of Emotional Pictures.

  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.

  0,1,28 days

Secondary Outcomes (2)

• Score on the Hamilton Anxiety Scale

  0, 7, 28 days

• Score on the Penn State Worry Scale

  0, 7, 28 days

Other Outcomes (1)

• Score on Quick Inventory of Depressive Symptomatology

  0, 7, 28 days

Study Arms (2)

alprazolam

EXPERIMENTAL

Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder.

Drug: Alprazolam (Xanax)

placebo

PLACEBO COMPARATOR

A placebo comparator will be administered to 12 patients with generalized anxiety disorder

Drug: Placebo

Interventions

Alprazolam (Xanax) DRUG

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).

Also known as: Xanax

alprazolam

Placebo DRUG

Placebo, bid, p.o. for 28 +/- 2 days.

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• Current use of herbal medication for mood or anxiety disorders and unwillingness to discontinue use for the duration of the study
• Current use of fluoxetine
• 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
• Past intolerance (including allergic) to, or clear history of non-response to the study medication

Sponsors & Collaborators

• University of California, San Diego: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

Related Publications (5)

• Paulus MP, Feinstein JS, Castillo G, Simmons AN, Stein MB. Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Arch Gen Psychiatry. 2005 Mar;62(3):282-8. doi: 10.1001/archpsyc.62.3.282.

  PMID: 15753241 BACKGROUND

• Salmeron BJ, Stein EA. Pharmacological applications of magnetic resonance imaging. Psychopharmacol Bull. 2002 Winter;36(1):102-29.

  PMID: 12397851 BACKGROUND

• Simmons A, Strigo I, Matthews SC, Paulus MP, Stein MB. Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects. Biol Psychiatry. 2006 Aug 15;60(4):402-9. doi: 10.1016/j.biopsych.2006.04.038.

  PMID: 16919527 BACKGROUND

• Baas JM, Grillon C, Bocker KB, Brack AA, Morgan CA 3rd, Kenemans JL, Verbaten MN. Benzodiazepines have no effect on fear-potentiated startle in humans. Psychopharmacology (Berl). 2002 May;161(3):233-47. doi: 10.1007/s00213-002-1011-8. Epub 2002 Mar 20.

  PMID: 12021826 BACKGROUND

• Grillon C, Baas JM, Pine DS, Lissek S, Lawley M, Ellis V, Levine J. The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle. Biol Psychiatry. 2006 Oct 1;60(7):760-6. doi: 10.1016/j.biopsych.2005.11.027. Epub 2006 Apr 21.

  PMID: 16631127 BACKGROUND

MeSH Terms

Conditions

Generalized Anxiety Disorder; Anxiety Disorders

Interventions

Alprazolam

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gregory G. Brown
• Organization: University of California San Diego

gbrown@ucsd.edu

858-246-0607

Study Officials

• Martin P Paulus, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 17, 2008
• First Posted: April 21, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: July 25, 2019
• Results First Posted: July 25, 2019

Record last verified: 2019-06

Locations

US (1)