Brain Inflammation in Major Depressive Disorder Background
|ClinicalTrials.gov Identifier: NCT01851356|
Recruitment Status : Completed
First Posted : May 10, 2013
Last Update Posted : June 13, 2018
- 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.
- To see if people with major depressive disorder have increased inflammation in the brain.
- Individuals at least 18 years of age who have major depressive disorder.
- 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.
|Condition or disease|
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.
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.
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.
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 Type :||Observational|
|Actual Enrollment :||61 participants|
|Official Title:||Brain Inflammation In Major Depressive Disorder|
|Study Start Date :||May 8, 2013|
|Actual Primary Completion Date :||July 27, 2017|
|Actual Study Completion Date :||March 22, 2018|
- Comparison of VT values obtained in MDD subject with those from healthy controls. [ Time Frame: single time point ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01851356
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Robert B Innis, M.D.||National Institute of Mental Health (NIMH)|