- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01322672
Peri-Anesthetic Imaging of Cognitive Dysfunction (PAICOD)
February 3, 2019 updated by: James L. Blair, Vanderbilt University
Peri-Anesthetic Imaging Compared With Neurocognitive Testing: A Pilot Study
Recent data suggests that anesthetics can have prolonged effects on gene expression, protein synthesis and processing as well as cellular function in ways that the investigators are only beginning to understand, especially in the very young and the elderly.
Within moments to days of emerging from anesthesia - cardiac or non-cardiac - some patients experience mild to very severe disorientation and changes in memory and thinking ability without apparent cause.
For the vast majority of patients, this Post-Operative Cognitive Dysfunction (POCD), generally subsides, but for some with "diminished cognitive reserve" - especially the elderly, those with less education or prior CNS events such as stroke or early dementia - changes in memory and executive function may persist.
If prolonged for more than three months, POCD has been linked to an increased risk of death.
In 1-2% of elderly patients, the problem may ultimately continue for more than a year, leading to a loss of ability to care for themselves and early demise.
Though this may seem like a small percentage, seniors will comprise up to 40% of the 50-75 million surgical procedures performed annually over the next 20-30 years.
This amounts to 70,000 - 200,000 elder affected, and for them and their families, the cost of POCD in longer-term care, lost wages, and extended suffering will remain very high.
Study Overview
Status
Completed
Detailed Description
For more than 160 years, "modern" anesthesia has provided immense benefit to patients of all ages.
However, over the past several years, concern has been growing that for patients at the extremes of age, some anesthetic agents may harbor subtle, previously minimally examined, serious neurotoxic effects which can cause lasting decline in the function of the central nervous system (CNS).
For the elderly, these effects may manifest in lasting post-operative deterioration of memory and the capacity for normal information processing that can result in the inability to perform the activities of daily living (ADLs) with eventual early demise.
Unfortunately, even though our ability to evaluate anesthetic risk has grown asymptotically for virtually every organ system, the brain remains neglected.
And even though we know a good deal about effect sites for general anesthetic agents, we still have an incomplete understanding of the potential toxic effects of anesthetics on the brain.
Therefore, employing a human surgical model (endoscopic prostatectomy), we propose a pilot study of 15 otherwise neurologically intact, ASA I - III, males, 65+ year of age.
After pre-enrollment screening (MMSE & BDI) and standard pre-op evaluation, subjects will undergo both anatomic and functional MRI studies plus a battery of neurocognitive tests (NCT) at two time points approximately 2-3 weeks apart prior to surgery.
These pre-op studies will establish both a "non-surgical control" for the study as well as a baseline for post-op studies.
2-3 weeks after surgery, MRI and NCT will be repeated.
The study aims to determine if MRI can demonstrate changes in the CNS pre-op vs post-op that relate to anesthesia and surgery and how those changes might correlate with NCT over the same interval.
Study Type
Observational
Enrollment (Actual)
6
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
65 years to 95 years (Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Subjects will be non-rheumatoid, non-immune-compromised, males and females, 65+ years old, scheduled for open abdominal surgery under general anesthesia of 3+ hour's duration.
Description
Inclusion Criteria:
- Age 65+ years; ASA I - III; capable and willing to consent
- Scheduled for 3+ hour Endoscopic Prostatectomy under general anesthesia
- Baseline MMSE > 20 (exclude dementia)
- All suitable for MRI testing
Exclusion Criteria:
- Hx Autoimmune Disease
- Severe visual or auditory disorder/handicaps
- Unable to read or understand English
- Pre-existing cognitive impairment; e.g., MS, AD or Parkinson's Disease, etc.
- Patients not expected to be able to complete the 2-3 week postoperative testing
- Major psychiatric condition such as bipolar disorder, schizophrenia
- Severe Panic Disorder
- Any implanted ferrous metal
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of preoperative vs postoperative Brain MRI changes
Time Frame: 2 months
|
Anesthetics can have prolonged effects on gene expression, protein synthesis and processing as well as cellular function, especially in the very young and the elderly.
After anesthesia, some patients experience mild to very severe disorientation and even delirium without apparent cause.
In the elderly, this Post-Operative Cognitive Dysfunction (POCD) - including changes in memory and executive function may persist and has been linked to an increased risk of death.
Over the next 20-30 years, 40% of 65+ year-olds will undergo surgery; the cost of POCD in longer-term care, lost wages, and extended suffering of patients and families will remain high.
|
2 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Preoperative vs Postoperative Neurocognitive Testing
Time Frame: 2 Months
|
Pre- vs postoperative Neurocognitive Testing (NCT) is currently the primary method used to quantify changes in cognitive indices, including memory, processing speed, motor function, etc.
This study will compare such pre- and post-op NCT with pre-and post-op MRI and fMRI to determine relationships between changes in each of these modalities.
|
2 Months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: James L Blair, DO, Vanderbilt University Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30. doi: 10.1097/01.anes.0000296071.19434.1e.
- Newman S, Stygall J, Hirani S, Shaefi S, Maze M. Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. Anesthesiology. 2007 Mar;106(3):572-90. doi: 10.1097/00000542-200703000-00023.
- Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT; ISPOCD2(International Study of Postoperative Cognitive Dysfunction) Investigators. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6. doi: 10.1034/j.1399-6576.2003.00057.x.
- Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
- Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008 Mar;1124:1-38. doi: 10.1196/annals.1440.011.
- Tucker AM, Stern Y. Cognitive reserve in aging. Curr Alzheimer Res. 2011 Jun;8(4):354-60. doi: 10.2174/156720511795745320.
- Perouansky M, Hemmings HC Jr. Neurotoxicity of general anesthetics: cause for concern? Anesthesiology. 2009 Dec;111(6):1365-71. doi: 10.1097/ALN.0b013e3181bf1d61. No abstract available.
- Fudickar A, Peters S, Stapelfeldt C, Serocki G, Leiendecker J, Meybohm P, Steinfath M, Bein B. Postoperative cognitive deficit after cardiopulmonary bypass with preserved cerebral oxygenation: a prospective observational pilot study. BMC Anesthesiol. 2011 Mar 14;11:7. doi: 10.1186/1471-2253-11-7.
- Shioiri A, Kurumaji A, Takeuchi T, Matsuda H, Arai H, Nishikawa T. White matter abnormalities as a risk factor for postoperative delirium revealed by diffusion tensor imaging. Am J Geriatr Psychiatry. 2010 Aug;18(8):743-53. doi: 10.1097/JGP.0b013e3181d145c5.
- Teeling JL, Perry VH. Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience. 2009 Feb 6;158(3):1062-73. doi: 10.1016/j.neuroscience.2008.07.031. Epub 2008 Jul 25.
- Hudetz JA, Patterson KM, Byrne AJ, Pagel PS, Warltier DC. Postoperative delirium is associated with postoperative cognitive dysfunction at one week after cardiac surgery with cardiopulmonary bypass. Psychol Rep. 2009 Dec;105(3 Pt 1):921-32. doi: 10.2466/PR0.105.3.921-932.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2011
Primary Completion (Actual)
August 27, 2015
Study Completion (Actual)
August 27, 2015
Study Registration Dates
First Submitted
March 23, 2011
First Submitted That Met QC Criteria
March 23, 2011
First Posted (Estimate)
March 24, 2011
Study Record Updates
Last Update Posted (Actual)
February 5, 2019
Last Update Submitted That Met QC Criteria
February 3, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB#100885
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Delirium
-
Efficacy Care R&D LtdHadassah Medical OrganizationUnknownDelirium | Delirium, Cause Unknown | Delirium of Mixed Origin | Delirium Confusional State | Delirium Drug-InducedIsrael
-
Imperial College Healthcare NHS TrustRecruitingCardiac Surgery | Intensive Care Unit Delirium | Post Operative DeliriumUnited Kingdom
-
Oslo University HospitalUniversity of Melbourne; Norwegian Academy of MusicRecruitingDelirium in Old Age | Delirium of Mixed Origin | Delirium Superimposed on Dementia | Delirium Confusional StateNorway
-
Menoufia UniversityCompleted
-
Universidad de SantanderUnknownDelirium of Mixed Origin | Hypoactive Delirium | Hyperactive DeliriumColombia
-
Chinese PLA General HospitalBeijing Tiantan HospitalRecruiting
-
Charite University, Berlin, GermanyBARMERRecruitingDelirium in Old AgeGermany
-
Mayo ClinicCompletedPost-Operative DeliriumUnited States
-
Johns Hopkins UniversityNational Institute on Aging (NIA)Active, not recruitingDelirium | Delirium on Emergence | Hearing Loss | Hearing Loss, High-Frequency | Hearing Loss, Sensorineural | Delirium, Cause Unknown | Hearing Loss, Bilateral | Hearing Disability | Delirium in Old Age | Delirium of Mixed Origin | Delirium Superimposed on Dementia | Delirium Confusional State | Delirium With... and other conditionsUnited States
-
University Hospital, Basel, SwitzerlandInnosuisse - Swiss Innovation AgencyRecruitingPostoperative Delirium (POD)Switzerland