Generalized Anxiety DisorderPhase 4GADNCT00662259
Drug Treatment Validation of Functional Magnetic Resonance Imaging in Generalized Anxiety Disorder
A Phase 4 study testing Alprazolam (Xanax) in people with Generalized Anxiety Disorder, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Generalized Anxiety Disorder
- What is being tested?
- Alprazolam (Xanax)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Sep 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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:
- 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
Who cannot join
- 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)
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- 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
- Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400 mg/d (approximately 4 cups of coffee or equivalent)
- Body mass index > 32.5 kg/m2
- Contraindication to magnetic resonance imaging based on a standard fMRI screening forms
- Concurrent participation in an institutional review board (IRB) approved investigational drug trial
- 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®)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92093
About this study
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
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.
Read the 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.
- Conditions
- Generalized Anxiety Disorder
- Being tested
- Alprazolam (Xanax), Placebo
- Keywords
- Anxiety disorders, Generalized anxiety
- Medical subject headings
- Generalized Anxiety Disorder, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alprazolam (Xanax)Drug
Also called 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).
PlaceboDrug
Placebo, bid, p.o. for 28 +/- 2 days.
| Study group | Role | What they receive |
|---|---|---|
| alprazolam | Experimental | Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder. Receives: Drug: Alprazolam (Xanax) |
| placebo | Placebo comparator | A placebo comparator will be administered to 12 patients with generalized anxiety disorder Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 0,1,28 days
Secondary outcomes (2)
Score on the Hamilton Anxiety Scale
Measured participant's general anxiety; range 0 - 56; higher scores worse
Measured: 0, 7, 28 days
Score on the Penn State Worry Scale
Measured participant's extent of worry; range 16 - 80, higher scores worse
Measured: 0, 7, 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2008 (estimated)
- Study startApr 2008
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Generalized Anxiety DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Principal investigator, Gregory G. Brown, University of California, San Diego
- Investigators
- Martin P Paulus, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00662259
- Sponsor's protocol ID
- WP21030
- Acronym
- GAD
- Status last verified
- Jun 2019
- First submitted
- 17 Apr 2008
- Last updated
- 25 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 15753241Salmeron BJ, Stein EA. Pharmacological applications of magnetic resonance imaging. Psychopharmacol Bull. 2002 Winter;36(1):102-29.
PubMed 12397851Simmons 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.
PubMed 16919527Baas 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.
PubMed 12021826Grillon 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.
PubMed 16631127
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00662259
- Acronym / sponsor ID
- GAD / WP21030
- Conditions
- Generalized Anxiety Disorder
- Keywords
- Anxiety disorders, Generalized anxiety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Apr 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 21 Apr 2008 (estimated)
- Results
- Posted 25 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| alprazolam | Experimental | Drug: Alprazolam (Xanax)Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder. |
| placebo | Placebo comparator | Drug: PlaceboA placebo comparator will be administered to 12 patients with generalized anxiety disorder |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (20 listed)
- Axis I disorder other than stated above with the exception of the following permitted comorbidities:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alprazolam (Xanax)Also: XanaxDrug 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). | Drug | alprazolam |
| PlaceboPlacebo, bid, p.o. for 28 +/- 2 days. | Drug | placebo |
Primary outcome
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.
2 secondary outcomes
Score on the Hamilton Anxiety Scale
Time frame: 0, 7, 28 days
Score on the Penn State Worry Scale
Time frame: 0, 7, 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15753241Paulus 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.
- Background: PubMed 12397851Salmeron BJ, Stein EA. Pharmacological applications of magnetic resonance imaging. Psychopharmacol Bull. 2002 Winter;36(1):102-29.
- Background: PubMed 16919527Simmons 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.
- Background: PubMed 12021826Baas 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.
- Background: PubMed 16631127Grillon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin P Paulus, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alprazolam (Xanax) in people with Generalized Anxiety Disorder, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Signal Change in Brain Activity in the Amygdala When Viewing Emotional Faces (time frame: 0,1,28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00662259, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2019.