DepressionNCT01132872
PET Whole Body Distribution Studies Using [11C]CUMI
An observational study of Depression and Major Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Researchers studying new treatments for major depressive disorder are looking at how medications to treat depression act on the brain chemical serotonin, which interacts with specific serotonin receptors on brain cells. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Major Depression, Unipolar Depression
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2010to 12 Apr 2012
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be adults between 18-65 years old.
- Subjects must be able and willing to give written informed consent.
Who cannot join
- With the exception of substance abuse disorders, any past or current Axis I diagnosis as assessed by clinical interview which may include the SCID-NP. With regard to substance abuse, we will allow a history of substance abuse so long as criteria for substance dependence are not met, and the episode(s) of substance abuse occurred over 1 year prior to study enrollment.
- Any prior use of Lysergic acid diethylamide (LSD).
- Use of ecstasy more than 3 times in a lifetime.
- Any history of psychotic symptoms.
- If female, any history of Premenstrual Dysphoric Disorder (PMDD), because PMDD has been shown to correlate with changes in 5-HT1A distribution in brain.
- In women, irregular menses such that the subject will not know the phase of the menstrual cycle at time of scanning.
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- Clinically significant laboratory abnormalities.
- Psychotropic medication use (including benzodiazepines and illicit drugs) during the 28 days (42 day for fluoxetine) prior to the PET scan.
- Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases or any cardiopulmonary disease that would increase risks associated with sedation.
- Positive HIV status.
- Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.
- History of fetal alcohol syndrome or other neurodevelopmental disorder.
- Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
- Positive urine drug screen.
- Inability to lie flat on camera bed for about 2.5 hours.
- Pregnancy at time of scan (beta HCG will be measured in all female patients within 24 hours of scan and must be negative).
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: PET Whole Body Distribution Studies Using the 5-HT1A Agonist, [11C]CUMI
Background:
- Researchers studying new treatments for major depressive disorder are looking at how medications to treat depression act on the brain chemical serotonin, which interacts with specific serotonin receptors on brain cells. New methods of studying serotonin receptors in the brain may help provide a better understanding of depression and treatment options.
- A new radioactive chemical called [11C]CUMI may be useful for studying serotonin receptors in the brain. By using positron emission tomography (PET) scanning to see how [11C]CUMI bonds with serotonin receptors, researchers will investigate whether [11C]CUMI can be used to study depression and how antidepressant medications work.
Read more
Objectives:
- To determine the usefulness of [11C]CUMI as a method of studying serotonin receptors in the brain.
Eligibility:
- Healthy individuals between 18 and 65 who have no history of psychiatric illness.
Design:
- This study requires 8 outpatient visits to the NIH clinic.
- Visit 1: Participants will have a full physical examination and medical history, as well as a psychiatric evaluation and questions about alcohol and drug use. Other tests will include blood and urine samples and an electrocardiogram (EKG). Testing will take approximately 3 hours.
- Visit 2: Participants will have a magnetic resonance imaging (MRI) scan to evaluate brain function and activity.
- Visit 3: Participants will have a PET scan, in which a small amount of the radioactive chemical [11C]CUMI will be injected through an intravenous (IV) catheter, and will have another IV line put in place to draw regular blood samples during the scan. The scan will last approximately 4 hours.
- Visits 4-8: Participants will have regular blood tests after the scan between days 1-3 and at about weeks 1, 2, 3, and 4. The blood tests will check muscle, heart, and liver function.
Read the detailed description
Eighteen million people in the United States are currently suffering from Major Depressive Disorder, which is characterized by episodes of low mood, poor self attitude and poor vitality. Of those suffering from Major Depressive Disorder (MDD), only one third completely improve, but even among these cases, there is a waiting period of several weeks or more during which antidepressants take effect. Our inability to adequately treat MDD is evident in its being ranked number one in Disability Adjusted Life Years (DALY) among persons aged 15-44. Given this profound burden, improving our understanding of the molecular basis of MDD is of utmost importance in the development of novel antidepressant medications.
Serotoninergic neurotransmission is implicated in MDD, as demonstrated by the relative success of selective serotonin reuptake inhibitors (SSRIs). SSRIs block the reuptake of serotonin through the serotonin transporter, which then increases serotonin at the synaptic cleft. Serotonin then binds to 5-HT(1A) receptors, which are G-protein coupled receptors that are present both presynaptically and postsynaptically. Presynaptically, these receptors act as autoinhibitory receptors, triggering decreased firing rates and decreased serotonin release. This autoinhibitory mechanism is believed to be the reason why patients experience a delay in symptomatic improvement after initiation of SSRIs. Serotonin binding to postsynaptic receptors mediates symptomatic improvement of depression. Multiple positron emission tomography (PET) studies on 5-HT(1A) have been published. However, none of these studies use 5-HT(1A) agonists, which are specific for the high affinity, G-protein coupled and active state of the 5-HT(1A) receptor. We would therefore like to establish the use of the 5-HT(1A) radiolabelled agonist, [(11)C]CUMI, here at NIH.
The purpose of this study is to perform whole body PET studies in healthy volunteers in order to estimate radiation absorbed doses for [(11)C]CUMI. Future experiments will include studies on Major Depressive Disorder.
- Keywords
- Serotonin 1A Receptor, Positron Emission Tomograhy (PET), Dosimetry, Healthy Volunteer, HV
- Medical subject headings
- Depression, Depressive Disorder, Major, Depressive Disorder, Anxiety Disorders
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2010 (estimated)
- Study start30 Apr 2010
- Study completion12 Apr 2012
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 DepressionStudies of the same condition, open and under way.
- 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
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Marta Gozzi, Ph.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01132872
- Sponsor's protocol ID
- 100110
- Other IDs
- 10-M-0110
- Status last verified
- 12 Apr 2012
- First submitted
- 27 May 2010
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Alpert JE, Franznick DA, Hollander SB, Fava M. Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder. J Clin Psychiatry. 2004 Aug;65(8):1069-75.
PubMed 15323591Amsterdam JD. Gepirone, a selective serotonin (5HT1A) partial agonist in the treatment of major depression. Prog Neuropsychopharmacol Biol Psychiatry. 1992 May;16(3):271-80. doi: 10.1016/0278-5846(92)90079-t.
PubMed 1350353Amsterdam JD, Brunswick DJ, Gibertini M. Sustained efficacy of gepirone-IR in major depressive disorder: a double-blind placebo substitution trial. J Psychiatr Res. 2004 May-Jun;38(3):259-65. doi: 10.1016/j.jpsychires.2003.10.005.
PubMed 15003431
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
- PET Whole Body Distribution Studies Using the 5-HT1A Agonist, [11C]CUMI
- ClinicalTrials.gov ID
- NCT01132872
- Acronym / sponsor ID
- 100110
- Keywords
- Serotonin 1A Receptor, Positron Emission Tomograhy (PET), Dosimetry, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 30 Apr 2010
- Study completion
- 12 Apr 2012
- First posted
- 28 May 2010 (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.
Background:
- Researchers studying new treatments for major depressive disorder are looking at how medications to treat depression act on the brain chemical serotonin, which interacts with specific serotonin receptors on brain cells. New methods of studying serotonin receptors in the brain may help provide a better understanding of depression and treatment options.
- A new radioactive chemical called [11C]CUMI may be useful for studying serotonin receptors in the brain. By using positron emission tomography (PET) scanning to see how [11C]CUMI bonds with serotonin receptors, researchers will investigate whether [11C]CUMI can be used to study depression and how antidepressant medications work.
Objectives:
- To determine the usefulness of [11C]CUMI as a method of studying serotonin receptors in the brain.
Eligibility:
- Healthy individuals between 18 and 65 who have no history of psychiatric illness.
Design:
- This study requires 8 outpatient visits to the NIH clinic.
- Visit 1: Participants will have a full physical examination and medical history, as well as a psychiatric evaluation and questions about alcohol and drug use. Other tests will include blood and urine samples and an electrocardiogram (EKG). Testing will take approximately 3 hours.
- Visit 2: Participants will have a magnetic resonance imaging (MRI) scan to evaluate brain function and activity.
- Visit 3: Participants will have a PET scan, in which a small amount of the radioactive chemical [11C]CUMI will be injected through an intravenous (IV) catheter, and will have another IV line put in place to draw regular blood samples during the scan. The scan will last approximately 4 hours.
- Visits 4-8: Participants will have regular blood tests after the scan between days 1-3 and at about weeks 1, 2, 3, and 4. The blood tests will check muscle, heart, and liver function.
Detailed description
Eighteen million people in the United States are currently suffering from Major Depressive Disorder, which is characterized by episodes of low mood, poor self attitude and poor vitality. Of those suffering from Major Depressive Disorder (MDD), only one third completely improve, but even among these cases, there is a waiting period of several weeks or more during which antidepressants take effect. Our inability to adequately treat MDD is evident in its being ranked number one in Disability Adjusted Life Years (DALY) among persons aged 15-44. Given this profound burden, improving our understanding of the molecular basis of MDD is of utmost importance in the development of novel antidepressant medications.
Serotoninergic neurotransmission is implicated in MDD, as demonstrated by the relative success of selective serotonin reuptake inhibitors (SSRIs). SSRIs block the reuptake of serotonin through the serotonin transporter, which then increases serotonin at the synaptic cleft. Serotonin then binds to 5-HT(1A) receptors, which are G-protein coupled receptors that are present both presynaptically and postsynaptically. Presynaptically, these receptors act as autoinhibitory receptors, triggering decreased firing rates and decreased serotonin release. This autoinhibitory mechanism is believed to be the reason why patients experience a delay in symptomatic improvement after initiation of SSRIs. Serotonin binding to postsynaptic receptors mediates symptomatic improvement of depression. Multiple positron emission tomography (PET) studies on 5-HT(1A) have been published. However, none of these studies use 5-HT(1A) agonists, which are specific for the high affinity, G-protein coupled and active state of the 5-HT(1A) receptor. We would therefore like to establish the use of the 5-HT(1A) radiolabelled agonist, [(11)C]CUMI, here at NIH.
The purpose of this study is to perform whole body PET studies in healthy volunteers in order to estimate radiation absorbed doses for [(11)C]CUMI. Future experiments will include studies on Major Depressive Disorder.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
Key exclusion criteria (16 listed)
- With the exception of substance abuse disorders, any past or current Axis I diagnosis as assessed by clinical interview which may include the SCID-NP. With regard to substance abuse, we will allow a history of substance abuse so long as criteria for substance dependence are not met, and the episode(s) of substance abuse occurred over 1 year prior to study enrollment.
- Any prior use of Lysergic acid diethylamide (LSD).
- Use of ecstasy more than 3 times in a lifetime.
- Any history of psychotic symptoms.
- If female, any history of Premenstrual Dysphoric Disorder (PMDD), because PMDD has been shown to correlate with changes in 5-HT1A distribution in brain.
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 15323591Alpert JE, Franznick DA, Hollander SB, Fava M. Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder. J Clin Psychiatry. 2004 Aug;65(8):1069-75.
- Background: PubMed 1350353Amsterdam JD. Gepirone, a selective serotonin (5HT1A) partial agonist in the treatment of major depression. Prog Neuropsychopharmacol Biol Psychiatry. 1992 May;16(3):271-80. doi: 10.1016/0278-5846(92)90079-t.
- Background: PubMed 15003431Amsterdam JD, Brunswick DJ, Gibertini M. Sustained efficacy of gepirone-IR in major depressive disorder: a double-blind placebo substitution trial. J Psychiatr Res. 2004 May-Jun;38(3):259-65. doi: 10.1016/j.jpsychires.2003.10.005.
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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.
Marta Gozzi, Ph.D. principal investigator
National Institute of Mental Health (NIMH)
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 Depression and Major Depression, 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 2 inclusion and 16 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 NCT01132872, 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.