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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01903421
First received: July 11, 2013
Last updated: March 14, 2014
Last verified: July 2013
  Purpose

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 Alzheimer's disease. More so, nearly half of people that are 85 years or older have Alzheimer's 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 Alzheimer's disease.The proposed study investigates if elderly patients (70 years and older) undergoing spinal anesthesia (patient is awake or slightly sedated) are less likely to develop dementia and Alzheimer's 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 Alzheimer's disease. The particular strength of this study is that it takes into account whether the frequency and/or severity of dementia and Alzheimer's 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 Alzheimer's disease.


Condition Intervention
Alzheimer's Disease
Dementia
Drug: Spinal anesthesia group: bupivacaine 10-15mg
Drug: General anesthesia group: 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)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Change in the incidence and severity of early dementia after surgery. [ Time Frame: baseline, hospital discharge (3 day average), 3 months, 1 year, and 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: March 2014
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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: 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)

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

->70 yrs of age

  • Male or female
  • Scheduled urology (transurethral resection of prostate, transurethral resection of bladder tumor), orthopedic (total knee replacement, total hip replacement) or general surgery (hernia repair, lower abdominal surgery)
  • Signed informed consent and qualify for randomization to receive either General(inhalation) or Local (spinal)anesthesia Exclusion
  • Diagnosis of severe dementia
  • Medical or anatomical reasons that would disqualify a consenting patient from receiving surgery under either a spinal or general anesthetic
  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: 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
London Health Science Centre Not yet recruiting
London, Ontario, Canada, N6A 5A5
Contact: Davy Cheng, MD    (519) 663-3031    davy.cheng@uwo.ca   
Sub-Investigator: Davy Cheng, MD         
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: David Mazer, MD    416- 864-5825    mazerd@smh.toronto.on.ca   
Sub-Investigator: David Mazer, MD         
Toronto General Hospital, UHN Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: George Djaiani, MD    416-340-4800 ext 6205    george.djaiani@uhn.ca   
Principal Investigator: George Djaiani, MD         
Toronto General Hospital, University Health Network Not yet 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         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: George Djaiani, MD Toronto General Hospital, University Health Network
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01903421     History of Changes
Other Study ID Numbers: 13-6122-A
Study First Received: July 11, 2013
Last Updated: March 14, 2014
Health Authority: Canada: Health Canada

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

Additional relevant MeSH terms:
Anesthetics
Anesthetics, General
Anesthetics, Inhalation
Anesthetics, Intravenous
Anesthetics, Local
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Bupivacaine
Isoflurane
Propofol
Sevoflurane
Central Nervous System Agents
Central Nervous System Depressants
Hematologic Agents
Hypnotics and Sedatives
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014