Panic DisorderPhase 2/3NCT00118417

Therapies for Treatment-Resistant Panic Disorder Symptoms

A Phase 2/3 study testing Clonazepam, Sertraline and Cognitive behavioral therapy in people with Panic Disorder, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will determine the effectiveness of different treatments for panic disorder symptoms in individuals who still have symptoms after initial treatment with medication. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Panic Disorder
What is being tested?: Clonazepam, Sertraline and Cognitive behavioral therapy
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 1 siteUnited States
Study dates: Mar 1999to Oct 2007
Phase: Phase 2/3
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

Diagnosis of panic disorder

Who cannot join

History of bipolar disorder, schizophrenia, psychosis, or delusional disorders
Post-traumatic stress disorder diagnosis within 6 months prior to study entry
Current use of psychotropic medications
Current use of cognitive behavioral therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Treatment Refractory Panic Disorder

This study will determine the effectiveness of different treatments for panic disorder symptoms in individuals who still have symptoms after initial treatment with medication.

Read the detailed description

Panic disorder is a serious condition that may cause significant psychological and physical distress. Many patients with panic disorder remain symptomatic despite initial intervention. Unfortunately, little data is available to guide health care providers in "next-step" treatment approaches. This study will evaluate the effectiveness of treatments for individuals with panic disorder that is resistant to initial treatment with selective serotonin reuptake inhibitors (SSRIs).

This study will last 24 weeks and will comprise three phases. In Phase 1, participants will receive the SSRI sertraline for 6 weeks. Phase 1 will be used to determine participants' resistance to treatment. During Phase 1, participants will begin a medication schedule and symptom diary and will have weekly study visits to assess regimen adherence and any side effects they may be experiencing. In Phase 2, participants will be randomly assigned to 6 weeks of one of two treatments: sertraline at an elevated dose from that given in Phase 1 or a sertraline and placebo regimen. During Phase 2, participants will have 3 study visits. Self-report scales and diary entries will be used to assess panic disorder symptoms and medication side effects. In Phase 3, participants will be randomly assigned to receive either cognitive behavioral therapy (CBT) or sertraline and clonazepam for 12 weeks. All participants will have weekly study visits during Phase 3. Questionnaires and self-report scales will be used to assess participants at the end of Phase 3.

Study hypothesis: Combined selective serotonin reuptake inhibitors (SSRIs) and benzodiazepine treatment, increasing the dose of SSRI, and the addition of cognitive behavioral therapy (CBT) each may have benefits for patients with panic disorder who remain symptomatic after initial treatment with SSRIs.

Conditions: Panic Disorder
Being tested: Clonazepam, Sertraline, Cognitive behavioral therapy
Keywords: Selective serotonin reuptake inhibitor, Anxiety, Pharmacotherapy, Cognitive behavioral therapy, CBT
Medical subject headings: Panic Disorder, Anxiety Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ClonazepamDrug
Participants will receive clonazepam.
SertralineDrug
Participants will receive sertraline.
Cognitive behavioral therapyBehavioural
Participants will receive cognitive behavioral therapy

Study groups in NCT00118417
Study group	Role	What they receive
1	Experimental	Participants in phase II will receive sertraline, or an equivalent medication, up to 100 mg plus a placebo pill. Participants in phase III will receive the same medication with cognitive behavioral therapy. Receives: Drug: Sertraline; Behavioral: Cognitive behavioral therapy
2	Experimental	Participants in phase II will receive sertraline, or equivalent medication, up to 200 mg. Participants in phase III they will receive the same medication with flexible clonazepam augmentation. Receives: Drug: Clonazepam; Drug: Sertraline

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Measured: Measured at baseline and after Phase 1 (6 weeks)
Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Measured: Measured after Phase 1 (Week 6) and Phase 2 (Week 12)
Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Measured: Measured after Phase 2 (Week 12) and Phase 3 (Week 24)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 1999Oct 2007

First posted11 Jul 2005 (estimated)
Study startMar 1999
Primary completionOct 2007
Study completionOct 2007

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 (1)Papers the sponsor has linked to this study.
Other trials for Panic DisorderStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe 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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00118417
Sponsor's protocol ID: K23MH001831
Other IDs: K23MH001831, DSIR AT-CD
Status last verified: Jun 2014
First submitted: 6 Jul 2005
Last updated: 11 Jun 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Simon NM, Otto MW, Worthington JJ, Hoge EA, Thompson EH, Lebeau RT, Moshier SJ, Zalta AK, Pollack MH. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. J Clin Psychiatry. 2009 Nov;70(11):1563-70. doi: 10.4088/JCP.08m04485blu. Epub 2009 Oct 6.
PubMed 19814948

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Panic Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment Refractory Panic Disorder
ClinicalTrials.gov ID: NCT00118417
Acronym / sponsor ID: K23MH001831
Conditions: Panic Disorder
Keywords: Selective serotonin reuptake inhibitor, Anxiety, Pharmacotherapy, Cognitive behavioral therapy, CBT
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: Mar 1999
Primary completion: Oct 2007 (actual)
Study completion: Oct 2007 (actual)
First posted: 11 Jul 2005 (estimated)
Results: Posted 28 Jul 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will determine the effectiveness of different treatments for panic disorder symptoms in individuals who still have symptoms after initial treatment with medication.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Sertraline, Behavioral: Cognitive behavioral therapyParticipants in phase II will receive sertraline, or an equivalent medication, up to 100 mg plus a placebo pill. Participants in phase III will receive the same medication with cognitive behavioral therapy.
2	Experimental	Drug: Clonazepam, Drug: SertralineParticipants in phase II will receive sertraline, or equivalent medication, up to 200 mg. Participants in phase III they will receive the same medication with flexible clonazepam augmentation.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Diagnosis of panic disorder

Key exclusion criteria (4 listed)

History of bipolar disorder, schizophrenia, psychosis, or delusional disorders
Post-traumatic stress disorder diagnosis within 6 months prior to study entry
Current use of psychotropic medications
Current use of cognitive behavioral therapy

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
ClonazepamParticipants will receive clonazepam.	Drug	2
SertralineParticipants will receive sertraline.	Drug	1, 2
Cognitive behavioral therapyParticipants will receive cognitive behavioral therapy	Behavioural	1

Primary outcome

Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)
Time frame: Measured at baseline and after Phase 1 (6 weeks)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12)
Time frame: Measured after Phase 1 (Week 6) and Phase 2 (Week 12)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24)
Time frame: Measured after Phase 2 (Week 12) and Phase 3 (Week 24)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.

Results and safety

Results posted to the registry on 28 Jul 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sertraline / Increased Dose / Medication Optimization	39	21
Sertraline / + Placebo / Cognitive Behavior Therapy Augment.	0	0

Primary outcome: Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)

Time frame: Measured at baseline and after Phase 1 (6 weeks). Mean (Standard Deviation). Unit: Points on a scale

Measure	Moderate Sertraline Treatment n = 39
Value	4.3 (4.3)

Moderate Sertraline Treatment: p = 0.0000, t-test, 2 sided

Population analysed: Analyses in each study phase were for a modified intent to treat (ITT) sample, defined as all participants who had at least one on-treatment assessment during that phase.

Primary outcome: Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12)

Time frame: Measured after Phase 1 (Week 6) and Phase 2 (Week 12). Mean (Standard Deviation). Unit: Points on a scale

Measure	Increased Sertraline n = 11	Sertraline Plus Placebo n = 13
Value	2.36 (3.44)	2.31 (4.29)

Increased Sertraline vs Sertraline Plus Placebo: p = 0.97, t-test, 2 sided

Primary outcome: Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24)

Time frame: Measured after Phase 2 (Week 12) and Phase 3 (Week 24). Mean (Standard Deviation). Unit: Points on a scale

Measure	Medication Optimization n = 9	Augmented Cognitive Behavior Therapy n = 10
Value	3.78 (3.80)	2.9 (3.63)

Medication Optimization vs Augmented Cognitive Behavior Therapy: p = 0.061, t-test, 2 sided

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I: Sertraline	2 of 39 (5.1%)	33 of 39 (84.6%)	Not reported
Phase II: Cont. SSRI Plus Placebo OR Increased Dose SSRI Alone	0 of 24 (0%)	21 of 24 (87.5%)	Not reported
Phase III: Cont. Medication Plus CBT OR SSRI and Clonazepam	3 of 19 (15.8%)	15 of 19 (78.9%)	Not reported

Limitations and caveats (from the sponsor): Power in Phase 2 limited detection to a large effect size. High drop-out for increased SSRI dose may indicate poor tolerability. Effectiveness of adding an SSRI to initial CBT was unexamined, limiting generalization to community treatment decisions.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 19814948Simon NM, Otto MW, Worthington JJ, Hoge EA, Thompson EH, Lebeau RT, Moshier SJ, Zalta AK, Pollack MH. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. J Clin Psychiatry. 2009 Nov;70(11):1563-70. doi: 10.4088/JCP.08m04485blu. Epub 2009 Oct 6.
Click here for more information about the Center for Anxiety and Traumatic Stress Related DisordersLink provided by the sponsor.

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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.

Naomi M. Simon, MD, MSc principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Clonazepam, Sertraline and Cognitive behavioral therapy in people with Panic Disorder, run by Massachusetts General Hospital 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 1 inclusion and 4 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 11 Jun 2014. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 28 Jul 2009). 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?

Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6) (time frame: Measured at baseline and after Phase 1 (6 weeks)). The study lists 3 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 NCT00118417, which also lists 1 linked publication.

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 11 Jun 2014.