Major DepressionNCT01851356
Brain Inflammation in Major Depressive Disorder Background
An observational study of Major Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Studies have shown that inflammation plays an important role in depression. Brain inflammation may contribute to depression, and may make it more difficult to treat some kinds of depression with current therapies. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Major Depression
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2013to 22 Mar 2018
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For healthy volunteers
- Age 18 or older
- No serious current medical condition
- Able to give written informed consent.
- No prior diagnosis of drug or alcohol dependence.
- For patients
Show all 10Show fewer
- Age 18 or older
- Able to give written informed consent.
- Subjects will have met DSM-IV criteria for recurrent MDD in a current major depressive episode.
- -No prior diagnosis of drug or alcohol dependence.
Who cannot join
- For healthy volunteers
- Any current Axis I diagnosis
- Clinically significant laboratory abnormalities other than CRP.
- Subjects with autoimmune disorders
- HIV positive
- Subjects with current infections
Show all 42Show fewer
- Recent peripheral injury
- Smoking in the last 6 months, because smoking may cause a inflammatory responses
- Risk for MRI scan, such as a pacemaker or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments. Welders and metal workers are also at risk for injury because of possible small metal fragments in the eye of which they may be unaware.
- History of neurologic illness or injury with the potential to affect study data interpretation.
- Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
- Inability to lie flat on camera bed for at least two hours.
- Pregnancy or breast feeding.
- Able to get pregnant but does not use birth control.
- Non binder to PBR28 determined with a blood test or genotyping
- Positive urine drug screen on the day of the scan
- Subjects receiving treatment likely to impact inflammation (e.g., chronic antinflammatory drug treatment), statins or corticosteroids
- Significant MRI abnormalities of the brain.
- History of seizures, other than in childhood and related to fever.
- A history of drug or alcohol abuse within 6 months or a history of alcohol or drug dependence (excepting nicotine) within 3 years (DSM-IV criteria)
- For patients
- Previous radiation exposure (X-rays, PET scans etc.) that, together with study procedures, would exceed NIH RSC research limits.
- Claustrophobia to a degree that the subject would feel uncomfortable in the MRI machine.
- Cannot lie on their back for at least two hours.
- Smoking in the last 6 months, because smoking may cause a inflammatory responses
- Brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on an MRI scan.
- Risk for MRI scan, such as a pacemaker or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments. Welders and metal workers are also at risk for injury because of possible small metal fragments in the eye of which they may be unaware.
- Subjects meet criteria for bipolar disorder or schizophrenia
- Current serious suicidal ideation (e.g., thoughts of attempting suicide along with the intent or plan to attempt suicide) or recent suicidal behavior (i.e., a suicide attempt within the past six months)
- Current psychosis
- Medical conditions or current medications that are likely to influence cerebral function or radiotracer delivery including cardiovascular, cerebrovascular, endocrine or neurological diseases
- A history of drug or alcohol abuse within 6 months or a history of alcohol or drug dependence (excepting nicotine) within 3 years (DSM-IV criteria)
- Current pregnancy or breastfeeding
- Able to get pregnant but does not use birth control
- Subjects with autoimmune disorders
- Subjects with current infections
- HIV positive
- Recent peripheral injury
- Subjects receiving treatment likely to impact inflammation (e.g., chronic antinflammatory drug treatment), statins or corticosteroids
- Subjects unable to travel independently to participate in the research study because of the severity of their depression.
- Non binder to PBR28 determined with a blood test or genotyping
- Positive urine drug screen on the day of the scan.
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: Brain Inflammation In Major Depressive Disorder
Background:
- Studies have shown that inflammation plays an important role in depression. Brain inflammation may contribute to depression, and may make it more difficult to treat some kinds of depression with current therapies. Researchers want to use magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning to study inflammation in the brain. To do so, they will use a contrast agent, which is a chemical that can show inflammation during an imaging study.
Read more
Objectives:
- To see if people with major depressive disorder have increased inflammation in the brain.
Eligibility:
- Individuals at least 18 years of age who have major depressive disorder.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood samples before the scanning sessions.
- Participants will have a PET scan after the screening visit. They will have a dose of the contrast agent before the study. This scan will look for possible brain inflammation.
- Participants will also have an MRI scan. This scan will take pictures of the brain for comparison studies.
- Treatment will not be provided as part of this study.
Read the detailed description
OBJECTIVE:
Inflammation in the periphery and in brain may be a predisposing factor for major depressive disorder (MDD). For example, MDD (even in the absence of medical illness) is often associated with raised inflammatory markers, and inflammatory medical illnesses are associated with greater rates of MDD. Moreover, patients treated with cytokines for various illnesses are at increased risk of developing MDD.
Translocator protein 18 kDa (TSPO) is a highly expressed protein in inflammatory cells of the brain: activated microglia and reactive astrocytes in brain. TSPO is, thereby, a potential biomarker of neuroinflammation. This protein can be accurately quantified using positron emission tomography (PET) and [C(11)]PBR28, a TSPO tracer synthesized in our laboratory.
The aim of this study is to assess whether subjects with MDD have increased TSPO binding in brain as an indirect marker of neuroinflammation.
STUDY POPULATION:
This protocol will study up to 40 patients with MDD and 30 healthy volunteers. We will recruit up to 40 MDD subjects to achieve 30 completers. The remaining 10 MMD subjects included in the total - account for subjects who sign consent (and therefore contribute to the accrual ceiling) but do not complete the study for a variety of reasons.
About half of the MDD subjects will be taking antidepressant medication and half will be unmedicated.
We will exclude subjects (approximately 10% of the population) that have low affinity for PBR28 ( non-binders ), based on a blood test or genotyping.
All healthy volunteers must not have any current serious medical condition.
DESIGN
For absolute quantification of TSPO, both MDD subjects and healthy controls will have arterial blood sampling concurrent with PET imaging using 11C-PBR28. We will try to minimize the recruitment of new healthy controls by relying on our historical database of healthy controls already scanned with [C(11)]PBR28.
OUTCOME MEASURES:
To assess absolute quantitation of TSPO with 11C-PBR28, we will primarily use the distribution volume (VT) calculated with compartmental modeling. As the primary goal, we will compare VT values obtained in MDD subjects with those from healthy controls. As secondary goals, we will assess 1) the effects of medication treatment in the MDD patients and 2) the relationship between CRP levels and TSPO binding in both MDD patients and healthy subjects.
- Conditions
- Major Depression
- Keywords
- PBR28, Depression, PET Imaging, Neuroinflammation
- Medical subject headings
- Depressive Disorder, Major, Depression, Neuroinflammatory Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of VT values obtained in MDD subject with those from healthy controls.
Measured: single time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start8 May 2013
- Primary completion27 Jul 2017
- Study completion22 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major 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
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851356
- Sponsor's protocol ID
- 130100
- Other IDs
- 13-M-0100
- Status last verified
- 22 Mar 2018
- First submitted
- 8 May 2013
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia. Lancet. 2001 Aug 11;358(9280):461-7. doi: 10.1016/S0140-6736(01)05625-2.
PubMed 11513911Banati RB, Myers R, Kreutzberg GW. PK ('peripheral benzodiazepine')--binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia. J Neurocytol. 1997 Feb;26(2):77-82. doi: 10.1023/a:1018567510105.
PubMed 9181482Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain. 2000 Nov;123 ( Pt 11):2321-37. doi: 10.1093/brain/123.11.2321.
PubMed 11050032Paul S, Gallagher E, Liow JS, Mabins S, Henry K, Zoghbi SS, Gunn RN, Kreisl WC, Richards EM, Zanotti-Fregonara P, Morse CL, Hong J, Kowalski A, Pike VW, Innis RB, Fujita M. Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.
PubMed 29749279
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Inflammation In Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT01851356
- Acronym / sponsor ID
- 130100
- Conditions
- Major Depression
- Keywords
- PBR28, Depression, PET Imaging, Neuroinflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 8 May 2013
- Primary completion
- 27 Jul 2017 (actual)
- Study completion
- 22 Mar 2018 (actual)
- First posted
- 10 May 2013 (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:
- Studies have shown that inflammation plays an important role in depression. Brain inflammation may contribute to depression, and may make it more difficult to treat some kinds of depression with current therapies. Researchers want to use magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning to study inflammation in the brain. To do so, they will use a contrast agent, which is a chemical that can show inflammation during an imaging study.
Objectives:
- To see if people with major depressive disorder have increased inflammation in the brain.
Eligibility:
- Individuals at least 18 years of age who have major depressive disorder.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood samples before the scanning sessions.
- Participants will have a PET scan after the screening visit. They will have a dose of the contrast agent before the study. This scan will look for possible brain inflammation.
- Participants will also have an MRI scan. This scan will take pictures of the brain for comparison studies.
- Treatment will not be provided as part of this study.
Detailed description
OBJECTIVE:
Inflammation in the periphery and in brain may be a predisposing factor for major depressive disorder (MDD). For example, MDD (even in the absence of medical illness) is often associated with raised inflammatory markers, and inflammatory medical illnesses are associated with greater rates of MDD. Moreover, patients treated with cytokines for various illnesses are at increased risk of developing MDD.
Translocator protein 18 kDa (TSPO) is a highly expressed protein in inflammatory cells of the brain: activated microglia and reactive astrocytes in brain. TSPO is, thereby, a potential biomarker of neuroinflammation. This protein can be accurately quantified using positron emission tomography (PET) and [C(11)]PBR28, a TSPO tracer synthesized in our laboratory.
The aim of this study is to assess whether subjects with MDD have increased TSPO binding in brain as an indirect marker of neuroinflammation.
STUDY POPULATION:
This protocol will study up to 40 patients with MDD and 30 healthy volunteers. We will recruit up to 40 MDD subjects to achieve 30 completers. The remaining 10 MMD subjects included in the total - account for subjects who sign consent (and therefore contribute to the accrual ceiling) but do not complete the study for a variety of reasons.
About half of the MDD subjects will be taking antidepressant medication and half will be unmedicated.
We will exclude subjects (approximately 10% of the population) that have low affinity for PBR28 ( non-binders ), based on a blood test or genotyping.
All healthy volunteers must not have any current serious medical condition.
DESIGN
For absolute quantification of TSPO, both MDD subjects and healthy controls will have arterial blood sampling concurrent with PET imaging using 11C-PBR28. We will try to minimize the recruitment of new healthy controls by relying on our historical database of healthy controls already scanned with [C(11)]PBR28.
OUTCOME MEASURES:
To assess absolute quantitation of TSPO with 11C-PBR28, we will primarily use the distribution volume (VT) calculated with compartmental modeling. As the primary goal, we will compare VT values obtained in MDD subjects with those from healthy controls. As secondary goals, we will assess 1) the effects of medication treatment in the MDD patients and 2) the relationship between CRP levels and TSPO binding in both MDD patients and healthy subjects.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- For healthy volunteers
- Age 18 or older
- No serious current medical condition
- Able to give written informed consent.
- No prior diagnosis of drug or alcohol dependence.
Key exclusion criteria (42 listed)
- For healthy volunteers
- Any current Axis I diagnosis
- Clinically significant laboratory abnormalities other than CRP.
- Subjects with autoimmune disorders
- HIV positive
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
Comparison of VT values obtained in MDD subject with those from healthy controls.
Time frame: single time point
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 16 Dec 2019.
- Background: PubMed 11513911Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia. Lancet. 2001 Aug 11;358(9280):461-7. doi: 10.1016/S0140-6736(01)05625-2.
- Background: PubMed 9181482Banati RB, Myers R, Kreutzberg GW. PK ('peripheral benzodiazepine')--binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia. J Neurocytol. 1997 Feb;26(2):77-82. doi: 10.1023/a:1018567510105.
- Background: PubMed 11050032Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain. 2000 Nov;123 ( Pt 11):2321-37. doi: 10.1093/brain/123.11.2321.
- Derived from this study: PubMed 29749279Paul S, Gallagher E, Liow JS, Mabins S, Henry K, Zoghbi SS, Gunn RN, Kreisl WC, Richards EM, Zanotti-Fregonara P, Morse CL, Hong J, Kowalski A, Pike VW, Innis RB, Fujita M. Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.
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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.
Robert B Innis, M.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 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 10 inclusion and 42 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 16 Dec 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. 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.
What does the primary outcome measure?
Comparison of VT values obtained in MDD subject with those from healthy controls. (time frame: single time point). 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 NCT01851356, which also lists 4 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 16 Dec 2019.