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Inhalational Anesthesia and Precipitation of Dementia: is There a Link?

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ClinicalTrials.gov Identifier: NCT01903421
Recruitment Status : Recruiting
First Posted : July 19, 2013
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
Many elderly patients undergoing surgical procedures already have impaired cognitive (memory/concentration) status. Patients with pre-existing cognitive impairment, or dementia, may benefit from modified anesthesia techniques. It is estimated that one in eight people age 65 and older has Alzheimers disease. More so, nearly half of people that are 85 years or older have Alzheimers disease. Currently, both spinal (regional) and inhalational (general) anesthesia, are used in patients undergoing common urological, orthopedic, and general surgical procedures. Inhalational anesthesia has been associated with higher risk of memory impairment in experimental (animal) and human studies. However, currently, there are simply no large or good enough studies to be sure that inhalational anesthesia is responsible for causing dementia and Alzheimers disease.The proposed study investigates if elderly patients (65 years and older) undergoing spinal anesthesia (patient is awake or slightly sedated) are less likely to develop dementia and Alzheimers disease for up to 2 years after surgery, when compared to inhalational anesthesia (patient is kept asleep with gas anesthetic). The investigators will also test all patients for the presence of apolipoprotein (ApoE-Îμ4 type of gene that is present in 15-20% of patients), and beta-amyloid tau protein (present in cerebrospinal fluid) that are known risk factors for Alzheimers disease. The particular strength of this study is that it takes into account whether the frequency and/or severity of dementia and Alzheimers disease is different in patients with and without these markers. The investigators believe that this study will make a major contribution to better understanding of development of Alzheimers disease.

Condition or disease Intervention/treatment
Alzheimer's Disease Dementia Drug: Spinal anesthesia group: bupivacaine 10-15mg Drug: General anesthesia group: induction propofol 1.5-2mg/kg and fentanyl 1-3g/kg, maintained with isoflurane or sevoflurane Genetic: Blood test Other: Lumbar spinal tap Behavioral: Montreal Cognitive Assessment (MOCA) and MMSE

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The proposed study will be a prospective, multicenter, cluster randomization clinical trial comparing two different anesthetic techniques in elderly patients (> 65 years of age) undergoing urology/orthopedic/general surgery. The study will follow a cluster design; patients undergoing orthopedic or vascular surgery will have spinal anesthesia, where standard practice. Patients undergoing urology or general surgery will receive general anesthesia, also where it is standard practice. Patients with severe dementia will be excluded.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Inhalational Anesthesia and Precipitation of Dementia: is There a Link? A Prospective, Multicenter, Randomized, Controlled Clinical Trial Comparing Two Different Anesthetic Techniques in Elderly Patients
Study Start Date : March 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Active Comparator: Spinal anesthesia group
Spinal anesthesia group will receive bupivacaine 10-15mg anesthesia according to the standard practice. Supplemental sedation with intravenous anesthetics (midazolam/propofol) will be optional.
Drug: Spinal anesthesia group: bupivacaine 10-15mg Genetic: Blood test
DNA will be tested for the presence of ε4 allele of the apolipoprotein E gene
Other: Lumbar spinal tap
1ml of cerebrospinal fluid (CSF) removed and stored for further analysis of amyloid tau protein after completion of the study
Behavioral: Montreal Cognitive Assessment (MOCA) and MMSE
Active Comparator: General anesthesia group
Induction of anesthesia will be achieved with propofol 1.5-2mg/kg and fentanyl 1-3g/kg. Anesthesia will be maintained with inhalational anesthesia (isoflurane or sevoflurane) at the discretion of anesthesiologist in charge of the case. A mixture of Air/O2 will be used to maintain adequate oxygenation. Nitrous oxide will not be used.
Drug: General anesthesia group: induction propofol 1.5-2mg/kg and fentanyl 1-3g/kg, maintained with isoflurane or sevoflurane Genetic: Blood test
DNA will be tested for the presence of ε4 allele of the apolipoprotein E gene
Other: Lumbar spinal tap
1ml of cerebrospinal fluid (CSF) removed and stored for further analysis of amyloid tau protein after completion of the study
Behavioral: Montreal Cognitive Assessment (MOCA) and MMSE



Primary Outcome Measures :
  1. Assessing the incidence of early dementia [ Time Frame: Change from baseline, hospital discharge (3 day average), 3 months, 1 year, and 2 years ]


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Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >65 yrs of age
  • Male or female
  • Scheduled to undergo urologic procedures (e.g., transurethral resection of prostate, transurethral resection of bladder tumor), orthopedic (e.g., total knee replacement, total hip replacement) general (e.g., femoral hernia repair, lower abdominal surgery) or vascular surgery procedures (e.g. lower limb reperfusion amputations) and qualifies to be randomized to receive either local (spinal) or general anesthetic

Exclusion Criteria:

  • Diagnosis of severe dementia
  • Diagnosis of any other significant neurological disease such as Parkinson's, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain or spinal abnormalities.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01903421


Contacts
Contact: George Djaiani, MD 416-340-4800 ext 6205 george.djaiani@uhn.ca
Contact: Jo Carroll 416-340-4800 ext 3243 jo.carroll@uhn.ca

Locations
Canada, Ontario
Toronto General Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: George Djaiani, MD    416-340-4800 ext 6205    george.djaiani@uhn.ca   
Principal Investigator: George Djaiani, MD         
Sub-Investigator: Rita Katznelson, MD         
Sub-Investigator: Rima Styra, MD         
Sub-Investigator: Frances Chung, MD         
William Osler Health Centre Not yet recruiting
Toronto, Ontario, Canada, M9V 1R8
Contact: Nazr Hegazy, MD    (647)973-5990    nasr.hegazy@williamoslerhs.ca   
Latvia
Pauls Stradins Clinical University Hospital Not yet recruiting
Riga, Latvia, LV 1002
Contact: Eva Strike, MD       evastrike@gmail.com   
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: George Djaiani, MD Toronto General Hospital, University Health Network

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01903421     History of Changes
Other Study ID Numbers: 13-6122-A
First Posted: July 19, 2013    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: November 2017

Keywords provided by University Health Network, Toronto:
Elderly surgical patients
Alzheimer's disease
Dementia
Elderly
Surgery

Additional relevant MeSH terms:
Anesthetics
Anesthetics, Local
Anesthetics, Intravenous
Anesthetics, General
Adjuvants, Anesthesia
Anesthetics, Inhalation
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Bupivacaine
Propofol
Fentanyl
Sevoflurane
Isoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Hypnotics and Sedatives
Analgesics, Opioid
Narcotics
Analgesics
Platelet Aggregation Inhibitors