Peri-Anesthetic Imaging of Cognitive Dysfunction (PAICOD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
James L. Blair, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01322672
First received: March 23, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition
Postoperative Cognitive Dysfunction
Delirium
Dementia
Neurotoxicity

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Peri-Anesthetic Imaging Compared With Neurocognitive Testing: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Comparison of preoperative vs postoperative Brain MRI changes [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Preoperative vs Postoperative Neurocognitive Testing [ Time Frame: 2 Months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 15
Study Start Date: March 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   65 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322672

Contacts
Contact: Damon R Michaels 615-343-6223 damon.michaels@vanderbilt.edu
Contact: Elizabeth Card 615-936-5354 elizabeth.card@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Sub-Investigator: Pratik P Pandharipande, MD, MSCI         
Sub-Investigator: John Gore, PhD         
Sub-Investigator: Baxter Rogers, PhD         
Sub-Investigator: Max Gunther, PhD         
Sub-Investigator: Joseph A Smith, MD         
Sub-Investigator: Jonathan Schildcrout, PhD         
Sub-Investigator: Catherine E Crenshaw Price, PhD         
Sub-Investigator: Yaping Shi, MS         
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: James L Blair, DO    615-343-9419 ext 343    james.l.blair@vanderbilt.edu   
Contact: Damon Michaels, BS    615-343-6223    damon.michaels@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: James L Blair, DO Vanderbilt University
  More Information

Publications:

Responsible Party: James L. Blair, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01322672     History of Changes
Other Study ID Numbers: IRB#100885
Study First Received: March 23, 2011
Last Updated: January 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Anesthetic Agents
POCD
Delirium
Cognitive Testing
Aging
Surgery
fMRI
Diffusion Tensor Imaging
White Matter

Additional relevant MeSH terms:
Cognition Disorders
Delirium
Neurotoxicity Syndromes
Chemically-Induced Disorders
Confusion
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Poisoning
Signs and Symptoms
Anesthetics
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014