Neurocognitive DisordersBBBSxNCT04566562
Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders
An observational study of Neurocognitive Disorders and Postoperative Cognitive Dysfunction, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Postoperative neurocognitive disorders (PND), which include postoperative delirium and both acute and longlasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Older adults are particularly at-risk of developing PND both in the short and long term. Read more about this study
- Who is it for?
- Ages 65 to 75 years
- Conditions the study is for
- Neurocognitive Disorders, Postoperative Cognitive Dysfunction
- What is being tested?
- Brain Imaging, Cognitive Testing and Blood Biomarkers
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2020to 29 Feb 2024
- 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 65 to 75 years
- All sexes
- No healthy volunteers
- Older adult
Study population: Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic surgery.
Who may be able to join
- 65-75 years old
- Scheduled for abdominal, gynecologic or urological surgery
Who cannot join
- Subjects undergoing surgery with a previous history of stroke, myocardial infarction, current pregnancy (if female), diagnosed neuropsychological and neuropsychiatric diseases, airway or chest deformities that would interfere with breathing, chronic obstructive pulmonary disease, cystic fibrosis, presence of space-occupying brain lesions, any history of drug abuse (e.g., cocaine or tobacco use), chronic kidney disease requiring dialysis.
- Body weight >300 pounds (restrictions of MRI scanner table).
- All subjects with any contraindication to the MRI procedures, such as metallic and electronic implants (phrenic or cardiac pacemakers), claustrophobia, metallic-based tattoos, will also be excluded. Non-english speaking patients will also be excluded as the cognitive tests have not been validated in other languages.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine
Los Angeles, California, 90095
About this study
Official title: Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders in Older Adults
Postoperative neurocognitive disorders (PND), which include postoperative delirium and both acute and longlasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Older adults are particularly at-risk of developing PND both in the short and long term. Although age is consistently reported as an important risk factor, the exact pathophysiology of PND remains poorly understood, but may include postsurgery-compromised blood brain barrier (BBB) function. This project proposes that perioperative BBB dysfunction is associated with measurable brain morphologic findings in cognitive control areas that can be discovered with non-invasive magnetic resonance imaging (MRI). Patients scheduled for surgery with an age range of 65-75 years of age, will participate in brain diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) and diffusion tensor imaging (DTI), cognitive assessments, and evaluation of a BBB marker from blood (at baseline, at two weeks, and at six months after surgery).
All patients will have a brain scan (MRI) within before surgery and two weeks and six months after surgery. During this visit cognitive function will be assessed. Patients will also be asked to participate in a blood draw.
Read the detailed description
The investigators will examine the potential mechanisms contributing to PND in an older surgical population. It is proposed that BBB will be altered contributing to brain tissue changes in cognitive control areas that can be examined with MD measures and blood biomarkers. Therefore, the specific aims are to:
AIM #1: Examine BBB function, using DW-pCASL procedures, and BBB marker (S100β levels), in older adult subjects between pre- ) and post-surgery
AIM #2: Assess brain tissue changes, using DTI-based MD measures, and cognition function, between pre- and post-surgery in older adult subjects.
AIM #3: Examine the relationships between BBB blood biomarker, BBB function index, and MD values from cognitive control areas (prefrontal cortex, caudate, and hippocampus) between pre- and post-surgery in an older surgical population.
A One-group comparative and longitudinal study design will be used in this proposal. A total of 34 older subjects scheduled for surgery will be recruited. Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic.
To assess cognitive function, the WRAML2 and MoCA tests will be performed within one week before surgery and at two weeks and six months after surgery. These tests have been used by our team in several conditions, and will be introduced just before MRI procedures. An average mean score of 100±15 on WRAML2 and a score ≥26 on MoCA will be considered normal.
Examination of BBB integrity from blood. To account for interindividual variation, baseline systemic biomarkers will be measured preoperatively (within one week before surgery). Postoperative samples will also be collected at two weeks and 6 months of surgery. Samples will be batch analyzed using Enzyme-linked immunosorbent assay (S100β) by the UCLA Department of Pathology \& Laboratory Medicine.
Magnetic Resonance Imaging. All brain MRI studies will be performed on a 3.0-Tesla MRI scanner (Siemens, Magnetom, Prisma) at the Department of Radiology, UCLA. MRI studies will be performed within one week before surgery, and at two weeks and six months after surgery.
- Being tested
- Brain Imaging, Cognitive Testing, Blood Biomarkers
- Keywords
- brain imaging, neurocognitive testing
- Medical subject headings
- Neurocognitive Disorders, Postoperative Cognitive Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain ImagingDiagnostic test
Magnetic Resonance Imaging (MRI) using diffusion weighted pseudo-continuous arterial spin labeling (DW-pCASL) .
Cognitive TestingDiagnostic test
Wide Range Assessment of Memory and Learning (WRAML 2) and Montreal Cognitive Assessment (MoCA)
Blood BiomarkersDiagnostic test
Inflammatory Markers
| Study group | Role | What they receive |
|---|---|---|
| Study Group | Brain scans, cognitive tests, blood biomarkers Receives: Diagnostic Test: Brain Imaging; Diagnostic Test: Cognitive Testing; Diagnostic Test: Blood Biomarkers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preoperative cognitive function
Montreal Cognitive Assessment (MoCA) test
Measured: pre-surgery (within five days before)
Postoperative cognitive dysfunction - delayed cognitive recovery
Montreal Cognitive Assessment (MoCA) test
Measured: Post-surgery (within two weeks post surgery)
Postoperative cognitive dysfunction - neurocognitive disorder
Montreal Cognitive Assessment (MoCA) test
Measured: Post-surgery (6 months after surgery)
Preoperative cognitive function II
Wide Range Assessment of Memory and Learning (WRAML2)
Measured: Pre-surgery (within five days before surgery)
Postoperative cognitive dysfunction - delayed cognitive recovery II
Wide Range Assessment of Memory and Learning (WRAML2)
Measured: Post-surgery (within two weeks post surgery)
Postoperative cognitive dysfunction - neurocognitive disorder II
Assessment of Memory and Learning (WRAML2)
Measured: Post-surgery (6 months after surgery)
Secondary outcomes (5)
Blood Serum anti-inflammatory Biomarkers
Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay
Measured: pre- (within five days before surgery)
Blood Serum anti-inflammatory Biomarkers II
Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay
Measured: post-surgery (within two weeks of surgery)
Brain changes
Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
Measured: pre- surgery (within five days before)
Brain changes II
non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
Measured: Post-surgery (within two days post surgery)
Brain changes III
Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
Measured: Post-surgery (within six months post surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start3 Aug 2020
- Primary completion30 Jan 2024
- Study completion29 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurocognitive DisordersStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rajesh Kumar, PhD, University of California, Los Angeles
- Investigators
- Rajesh Kumar, Ph.D, Principal investigator, rkumar@mednet.ucla.eduSusana Vacas, M.D., Ph.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04566562
- Sponsor's protocol ID
- BBBSx 20-001456
- Acronym
- BBBSx
- Status last verified
- Aug 2024
- First submitted
- 22 Sep 2020
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders in Older Adults
- ClinicalTrials.gov ID
- NCT04566562
- Acronym / sponsor ID
- BBBSx / BBBSx 20-001456
- Keywords
- brain imaging, neurocognitive testing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 3 Aug 2020 (actual)
- Primary completion
- 30 Jan 2024 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 28 Sep 2020 (actual)
- 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.
Postoperative neurocognitive disorders (PND), which include postoperative delirium and both acute and longlasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Older adults are particularly at-risk of developing PND both in the short and long term. Although age is consistently reported as an important risk factor, the exact pathophysiology of PND remains poorly understood, but may include postsurgery-compromised blood brain barrier (BBB) function. This project proposes that perioperative BBB dysfunction is associated with measurable brain morphologic findings in cognitive control areas that can be discovered with non-invasive magnetic resonance imaging (MRI). Patients scheduled for surgery with an age range of 65-75 years of age, will participate in brain diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) and diffusion tensor imaging (DTI), cognitive assessments, and evaluation of a BBB marker from blood (at baseline, at two weeks, and at six months after surgery).
All patients will have a brain scan (MRI) within before surgery and two weeks and six months after surgery. During this visit cognitive function will be assessed. Patients will also be asked to participate in a blood draw.
Detailed description
The investigators will examine the potential mechanisms contributing to PND in an older surgical population. It is proposed that BBB will be altered contributing to brain tissue changes in cognitive control areas that can be examined with MD measures and blood biomarkers. Therefore, the specific aims are to:
AIM #1: Examine BBB function, using DW-pCASL procedures, and BBB marker (S100β levels), in older adult subjects between pre- ) and post-surgery
AIM #2: Assess brain tissue changes, using DTI-based MD measures, and cognition function, between pre- and post-surgery in older adult subjects.
AIM #3: Examine the relationships between BBB blood biomarker, BBB function index, and MD values from cognitive control areas (prefrontal cortex, caudate, and hippocampus) between pre- and post-surgery in an older surgical population.
A One-group comparative and longitudinal study design will be used in this proposal. A total of 34 older subjects scheduled for surgery will be recruited. Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic.
To assess cognitive function, the WRAML2 and MoCA tests will be performed within one week before surgery and at two weeks and six months after surgery. These tests have been used by our team in several conditions, and will be introduced just before MRI procedures. An average mean score of 100±15 on WRAML2 and a score ≥26 on MoCA will be considered normal.
Examination of BBB integrity from blood. To account for interindividual variation, baseline systemic biomarkers will be measured preoperatively (within one week before surgery). Postoperative samples will also be collected at two weeks and 6 months of surgery. Samples will be batch analyzed using Enzyme-linked immunosorbent assay (S100β) by the UCLA Department of Pathology \& Laboratory Medicine.
Magnetic Resonance Imaging. All brain MRI studies will be performed on a 3.0-Tesla MRI scanner (Siemens, Magnetom, Prisma) at the Department of Radiology, UCLA. MRI studies will be performed within one week before surgery, and at two weeks and six months after surgery.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Group | – | Diagnostic Test: Brain Imaging, Diagnostic Test: Cognitive Testing, Diagnostic Test: Blood BiomarkersBrain scans, cognitive tests, blood biomarkers |
Who may qualify
- Ages
- 65 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic surgery.
Key inclusion criteria (2 listed)
- 65-75 years old
- Scheduled for abdominal, gynecologic or urological surgery
Key exclusion criteria (3 listed)
- Subjects undergoing surgery with a previous history of stroke, myocardial infarction, current pregnancy (if female), diagnosed neuropsychological and neuropsychiatric diseases, airway or chest deformities that would interfere with breathing, chronic obstructive pulmonary disease, cystic fibrosis, presence of space-occupying brain lesions, any history of drug abuse (e.g., cocaine or tobacco use), chronic kidney disease requiring dialysis.
- Body weight >300 pounds (restrictions of MRI scanner table).
- All subjects with any contraindication to the MRI procedures, such as metallic and electronic implants (phrenic or cardiac pacemakers), claustrophobia, metallic-based tattoos, will also be excluded. Non-english speaking patients will also be excluded as the cognitive tests have not been validated in other languages.
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 |
|---|---|---|
| Brain ImagingMagnetic Resonance Imaging (MRI) using diffusion weighted pseudo-continuous arterial spin labeling (DW-pCASL) . | Diagnostic test | Study Group |
| Cognitive TestingWide Range Assessment of Memory and Learning (WRAML 2) and Montreal Cognitive Assessment (MoCA) | Diagnostic test | Study Group |
| Blood BiomarkersInflammatory Markers | Diagnostic test | Study Group |
Primary outcome
Preoperative cognitive function
Time frame: pre-surgery (within five days before)
Montreal Cognitive Assessment (MoCA) test
Postoperative cognitive dysfunction - delayed cognitive recovery
Time frame: Post-surgery (within two weeks post surgery)
Montreal Cognitive Assessment (MoCA) test
Postoperative cognitive dysfunction - neurocognitive disorder
Time frame: Post-surgery (6 months after surgery)
Montreal Cognitive Assessment (MoCA) test
Preoperative cognitive function II
Time frame: Pre-surgery (within five days before surgery)
Wide Range Assessment of Memory and Learning (WRAML2)
Postoperative cognitive dysfunction - delayed cognitive recovery II
Time frame: Post-surgery (within two weeks post surgery)
Wide Range Assessment of Memory and Learning (WRAML2)
Postoperative cognitive dysfunction - neurocognitive disorder II
Time frame: Post-surgery (6 months after surgery)
Assessment of Memory and Learning (WRAML2)
5 secondary outcomes
Blood Serum anti-inflammatory Biomarkers
Time frame: pre- (within five days before surgery)
Blood Serum anti-inflammatory Biomarkers II
Time frame: post-surgery (within two weeks of surgery)
Brain changes
Time frame: pre- surgery (within five days before)
Brain changes II
Time frame: Post-surgery (within two days post surgery)
Brain changes III
Time frame: Post-surgery (within six months post surgery)
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 10 Dec 2024.
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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.
Rajesh Kumar, Ph.D principal investigator
rkumar@mednet.ucla.edu
Susana Vacas, M.D., Ph.D. 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?
An observational study of Neurocognitive Disorders and Postoperative Cognitive Dysfunction, run by University of California, Los Angeles 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 3 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 10 Dec 2024. 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?
Preoperative cognitive function (time frame: pre-surgery (within five days before)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2024.