Panic DisorderNCT00025974
Brain Chemical Receptor Effects in Patients With Panic Disorder and Post-Traumatic Stress Disorder
An observational study of Panic Disorder and Posttraumatic Stress Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
The purpose of this study is to examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Panic Disorder, Posttraumatic Stress Disorder, Major Depressive Disorder
- How many people
- 230 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2001to 21 Jul 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ANXIETY DISORDERS SAMPLES:
- Eighty four subjects (ages 18-50) with anxiety disorders (PD and PTSD) will be selected who additionally meet criteria for one of 4 subgroups:
- PD, Currently Depressed (n=27):
- As defined by DSM-IV criteria for PD, and still symptomatic as defined by at least 1 panic attack/week or a CGI score of at least 4, and current HDRS score in the mild-moderately-to-severely depressed range (greater than 15).
- Patients are requested to meet the DSM-IV criteria for a single or recurrent episode of major depressive disorder.
- In case of comorbid depression it will be ensured that PD had an earlier onset than the depressive disorder.
Show all 22Show fewer
- PD, Currently Not Depressed (n=27):
- Defined as having symptomatic PD with at least 1 panic attack/week or a CGI score of at least 4 and never having had experienced a depressive episode meeting DSM-IV criteria for major depressive disorder or dysthymia, OR a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent, with Hamilton Depression Rating Scale (HDRS; 25 item) scores in the non-depressed range (less than or equal to 7) will be selected.
- PTSD, Currently Depressed (n=15):
- As defined by DSM-IV with a duration of illness at least three months.
- Patients must score greater than or equal to 50 on Clinician-Administered PTSD Scale (CAPS-2) as a measure of PTSD symptom severity.
- Patients are requested to meet the DSM-IV criteria for a single or recurrent episode of major depressive disorder.
- Current HDRS score is in the mild-moderately-to-severely depressed range (greater than or equal to 15).
- In case of comorbid depression it will be ensured that PTSD had an earlier onset than the depressive disorder.
- PTSD, Currently Not Depressed (n=15):
- Defined as having PTSD and never having had experienced a depressive episode meeting DSM-IV criteria for major depressive disorder or dysthymia OR a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent, with Hamilton Depression Rating Scale (HDRS; 25 item) scores in the non-depressed range (less than or equal to 7) will be selected.
- HEALTHY CONTROL SAMPLE:
- One hundred sixteen subjects (ages 18-50) who have not met criteria for any major psychiatric disorder.
- The control subjects will have no known first-degree relatives with PD or PTSD.
- PSYCHIATRIC CONTROL SAMPLE (n=30):
- Subjects with Major Depressive Disorder (MDD), currently remitted, as defined by a period of at least three months during which the subject has not taken an antidepressant agent, with Hamilton Depression Rating Scales (HDRS; 21-item) scores in the non-depressed range (less than 8), and with no more than one clinically significant depressive symptom.
- These subjects must not have a history of PTSD and/or serious trauma.
Who cannot join
- Subjects will be recruited who are drug-naive or who are not currently receiving psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine). In case a patient is on psychotropic medications and this treatment is not successful (as defined by meeting the inclusion criteria as noted above), the medication will be tapered off to ensure that the subject is drug-free for at least 3 weeks prior to PET scanning.
- Subjects will be also be excluded if they have: a) serious suicidal ideation or behavior, b) psychosis to the extent that the ability to provide informed consent is in doubt, c) medical or neurological illnesses likely to affect physiology or anatomy, d) a history of drug (including BZDs) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria), e) current pregnancy (as documented by pregnancy testing prior to scanning), f) current breast feeding, g) general MRI exclusion criteria, h) patients who are currently taking fluoxetine.
- Patients and controls must exhibit no or only moderate alcohol use.
- Subjects with current or previous regular (greater than 4 weeks) of BZDs and excessive use of alcohol (greater than 8 ounce/day for men and greater than six ounces /day for women) in the past or present are ineligible to participate, as they may produce a down-regulation of the BZD receptor that may confound the results.
- Postmenopausal female subjects.
- Subjects beyond age 50 are excluded to reduce the biological heterogeneity encompassed by the MDD and anxiety disorders criteria.
- Subjects whose first anxiety disorder episode arose temporally after other major medical or psychiatric conditions will also be excluded.
- In addition to the above criteria, subjects undergoing the serotonin transporter scan will also be excluded if they have taken the recreational drug ecstasy within 3 weeks prior to scan or for regular use in the past.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Serotonin 1A Receptor Imaging and Benzodiazepine Receptor Imaging in Panic Disorder and Posttraumatic Stress Disorder
The purpose of this study is to examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD).
Brain chemicals that regulate emotion, anxiety, sleep, stress hormones, and other body functions bind to serotonin (5-HT1A) and benzodiazepine (BZD) receptors. Evidence suggests that 5-HT1A and BZD receptor function is abnormal in patients with PD, PTSD, and depression. This study will use positron emission tomography (PET) scans to examine BZD and 5-HT1A receptor binding potential in patients with PD and patients with PTSD with and without co-morbid MDD, as well as in healthy volunteers. This study will also determine the effects of the stress hormone cortisol on 5-HT1A and BZD receptors.
Read more
The current emotional state and psychiatric, medical, and family history of potential participants will be evaluated during an initial telephone interview. After entering the study, participants will be asked questions about general mood, degree of nervousness, and behavior. A physical examination, an electrocardiogram (EKG), and tests of intelligence and cognition will be given. Urine, blood, and saliva samples will be taken. Women will be given pregnancy tests and tests to determine menstrual phase and time of ovulation. All volunteers will undergo magnetic resonance imaging (MRI) and PET scans of the brain.
...
Read the detailed description
Evidence suggests that serotonin1A (5-HT1A) receptor, serotonin transporter (5-HTT) and benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic stress disorder (PTSD) and depression (MDD). The hypotheses for the role of 5-HT1A receptors have been obtained by assessing behavioral, neuroendocrine and temperature responses to the selective partial 5-HT1A agonist ipsapirone in anxiety disorders subjects and healthy controls, and examining effects on 5-HT1A receptor function in rats following antidepressant drug (AD) administration. 5-HT1A receptors knockout mice show behaviors that have been used as a model for anxiety disorders in humans. Moreover, 5-HT1A receptor agonists have been shown to be effective in the treatment of patients with anxiety disorders. The serotonin transporter is implicated in these disorders by virtue of the efficacy of selective serotonin reuptake inhibitors in relieving symptoms in these subjects. Evidence arguing for a role of BZD/GABA receptor dysfunction in anxiety disorders comes from studies showing anxiolytic and anxiogenic properties of BZD agonists and antagonists, respectively. BZD receptor sensitivity has been shown to be reduced in patients with anxiety disorders. Brain imaging studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) suggest decreased BZD receptor binding in PD and PTSD.
Animal studies link together serotonin and GABA suggesting a pathological pathway originating from 5-HT1A receptor deficit leading towards dysfunctions within GABAergic systems, resulting in increased levels of anxiety. Yet, association between disturbed interactions between 5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in humans. The proposed study will advance knowledge regarding the neurobiology of PD and PTSD by employing PET and [11C]flumazenil, [18F]FC-WAY100635([18F]FCWAY) and [11C]DASB to compare BZD receptor, 5-HT1A receptors and the serotonin transporter binding potential, respectively, between PD, PTSD and MDD patients and healthy controls. Because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion, assessments of HPA-axis activity will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in PD, PTSD and MDD.
The following hypotheses will be tested: 1) PD/PTSD/MDD patients have reduced GABA(A)-BZD receptor binding relative to healthy controls. 2) PD/PTSD/MDD patients have reduced 5-HT1A receptor binding potential relative to healthy controls. 3) 5-HT1A receptor binding will be more prominently reduced in PD and PTSD patients with comorbid MDD relative to anxiety disorders patients without comorbid MDD and healthy controls. 4) There will be a positive correlation between the reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients. 5) There will be an inverse correlation between reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients and cortisol secretion. 6) Serotonin transporter binding, measured using [11C]DASB, will be reduced in PD subjects relative to healthy controls.
- Keywords
- PET, 5-HT1A Receptors, Benzodiazepine Receptors, Panic Disorder, PTSD, Serotonin Type 1A Receptors, Post-Traumatic Stress Disorder, Major Depression, Anxiety, Depression, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Panic Disorder, Stress Disorders, Post-Traumatic, Depressive Disorder, Major, Anxiety Disorders, Depression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2001 (estimated)
- Study start31 Oct 2001
- Study completion21 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 National Institute of Mental Health (NIMH)The 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
- Observational
- Enrolment
- 230 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00025974
- Sponsor's protocol ID
- 020002
- Other IDs
- 02-M-0002
- Status last verified
- 21 Jul 2008
- First submitted
- 2 Nov 2001
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Azmitia EC, Whitaker-Azmitia PM. Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry. 1991 Dec;52 Suppl:4-16.
PubMed 1752858Sprouse JS, Aghajanian GK. Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology. 1988 Jul;27(7):707-15. doi: 10.1016/0028-3908(88)90079-2.
PubMed 2901680Chaput Y, de Montigny C. Effects of the 5-hydroxytryptamine receptor antagonist, BMY 7378, on 5-hydroxytryptamine neurotransmission: electrophysiological studies in the rat central nervous system. J Pharmacol Exp Ther. 1988 Jul;246(1):359-70.
PubMed 2839669
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serotonin 1A Receptor Imaging and Benzodiazepine Receptor Imaging in Panic Disorder and Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT00025974
- Acronym / sponsor ID
- 020002
- Keywords
- PET, 5-HT1A Receptors, Benzodiazepine Receptors, Panic Disorder, PTSD, Serotonin Type 1A Receptors, Post-Traumatic Stress Disorder, Major Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 230 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 31 Oct 2001
- Study completion
- 21 Jul 2008
- First posted
- 5 Nov 2001 (estimated)
- Results
- Not posted in the source record
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 examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD).
Brain chemicals that regulate emotion, anxiety, sleep, stress hormones, and other body functions bind to serotonin (5-HT1A) and benzodiazepine (BZD) receptors. Evidence suggests that 5-HT1A and BZD receptor function is abnormal in patients with PD, PTSD, and depression. This study will use positron emission tomography (PET) scans to examine BZD and 5-HT1A receptor binding potential in patients with PD and patients with PTSD with and without co-morbid MDD, as well as in healthy volunteers. This study will also determine the effects of the stress hormone cortisol on 5-HT1A and BZD receptors.
The current emotional state and psychiatric, medical, and family history of potential participants will be evaluated during an initial telephone interview. After entering the study, participants will be asked questions about general mood, degree of nervousness, and behavior. A physical examination, an electrocardiogram (EKG), and tests of intelligence and cognition will be given. Urine, blood, and saliva samples will be taken. Women will be given pregnancy tests and tests to determine menstrual phase and time of ovulation. All volunteers will undergo magnetic resonance imaging (MRI) and PET scans of the brain.
...
Detailed description
Evidence suggests that serotonin1A (5-HT1A) receptor, serotonin transporter (5-HTT) and benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic stress disorder (PTSD) and depression (MDD). The hypotheses for the role of 5-HT1A receptors have been obtained by assessing behavioral, neuroendocrine and temperature responses to the selective partial 5-HT1A agonist ipsapirone in anxiety disorders subjects and healthy controls, and examining effects on 5-HT1A receptor function in rats following antidepressant drug (AD) administration. 5-HT1A receptors knockout mice show behaviors that have been used as a model for anxiety disorders in humans. Moreover, 5-HT1A receptor agonists have been shown to be effective in the treatment of patients with anxiety disorders. The serotonin transporter is implicated in these disorders by virtue of the efficacy of selective serotonin reuptake inhibitors in relieving symptoms in these subjects. Evidence arguing for a role of BZD/GABA receptor dysfunction in anxiety disorders comes from studies showing anxiolytic and anxiogenic properties of BZD agonists and antagonists, respectively. BZD receptor sensitivity has been shown to be reduced in patients with anxiety disorders. Brain imaging studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) suggest decreased BZD receptor binding in PD and PTSD.
Animal studies link together serotonin and GABA suggesting a pathological pathway originating from 5-HT1A receptor deficit leading towards dysfunctions within GABAergic systems, resulting in increased levels of anxiety. Yet, association between disturbed interactions between 5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in humans. The proposed study will advance knowledge regarding the neurobiology of PD and PTSD by employing PET and [11C]flumazenil, [18F]FC-WAY100635([18F]FCWAY) and [11C]DASB to compare BZD receptor, 5-HT1A receptors and the serotonin transporter binding potential, respectively, between PD, PTSD and MDD patients and healthy controls. Because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion, assessments of HPA-axis activity will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in PD, PTSD and MDD.
The following hypotheses will be tested: 1) PD/PTSD/MDD patients have reduced GABA(A)-BZD receptor binding relative to healthy controls. 2) PD/PTSD/MDD patients have reduced 5-HT1A receptor binding potential relative to healthy controls. 3) 5-HT1A receptor binding will be more prominently reduced in PD and PTSD patients with comorbid MDD relative to anxiety disorders patients without comorbid MDD and healthy controls. 4) There will be a positive correlation between the reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients. 5) There will be an inverse correlation between reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients and cortisol secretion. 6) Serotonin transporter binding, measured using [11C]DASB, will be reduced in PD subjects relative to healthy controls.
Study design
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Eighty four subjects (ages 18-50) with anxiety disorders (PD and PTSD) will be selected who additionally meet criteria for one of 4 subgroups:
- PD, Currently Depressed (n=27):
- As defined by DSM-IV criteria for PD, and still symptomatic as defined by at least 1 panic attack/week or a CGI score of at least 4, and current HDRS score in the mild-moderately-to-severely depressed range (greater than 15).
- Patients are requested to meet the DSM-IV criteria for a single or recurrent episode of major depressive disorder.
- In case of comorbid depression it will be ensured that PD had an earlier onset than the depressive disorder.
Key exclusion criteria (8 listed)
- Subjects will be recruited who are drug-naive or who are not currently receiving psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine). In case a patient is on psychotropic medications and this treatment is not successful (as defined by meeting the inclusion criteria as noted above), the medication will be tapered off to ensure that the subject is drug-free for at least 3 weeks prior to PET scanning.
- Subjects will be also be excluded if they have: a) serious suicidal ideation or behavior, b) psychosis to the extent that the ability to provide informed consent is in doubt, c) medical or neurological illnesses likely to affect physiology or anatomy, d) a history of drug (including BZDs) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria), e) current pregnancy (as documented by pregnancy testing prior to scanning), f) current breast feeding, g) general MRI exclusion criteria, h) patients who are currently taking fluoxetine.
- Patients and controls must exhibit no or only moderate alcohol use.
- Subjects with current or previous regular (greater than 4 weeks) of BZDs and excessive use of alcohol (greater than 8 ounce/day for men and greater than six ounces /day for women) in the past or present are ineligible to participate, as they may produce a down-regulation of the BZD receptor that may confound the results.
- Postmenopausal female subjects.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 1752858Azmitia EC, Whitaker-Azmitia PM. Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry. 1991 Dec;52 Suppl:4-16.
- Background: PubMed 2901680Sprouse JS, Aghajanian GK. Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology. 1988 Jul;27(7):707-15. doi: 10.1016/0028-3908(88)90079-2.
- Background: PubMed 2839669Chaput Y, de Montigny C. Effects of the 5-hydroxytryptamine receptor antagonist, BMY 7378, on 5-hydroxytryptamine neurotransmission: electrophysiological studies in the rat central nervous system. J Pharmacol Exp Ther. 1988 Jul;246(1):359-70.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Panic Disorder and Posttraumatic Stress Disorder, run by National Institute of Mental Health (NIMH) 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 22 inclusion and 8 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 2 Jul 2017. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00025974, which also lists 3 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 2 Jul 2017.