Interaction of Cobalamin Status With Nitrous Oxide in Relation to Postoperative Cognitive Changes in the Elderly
Subtle Disturbances of Cobalamin Status
2 other identifiers
interventional
444
1 country
2
Brief Summary
Low cobalamin (vitamin B12) levels are frequent in the elderly. Most often they reflect a mild metabolic abnormality without clinical symptoms (subclinical cobalamin deficiency). It is unclear if these elderly people require medical intervention, unlike that small minority with clinical symptoms which can progress and create severe blood or nervous system problems. The study aims to determine if nitrous oxide (N2O), a common anesthetic agent, worsens cobalamin status in elderly patients with unrecognized subclinical cobalamin deficiency. The reason for concern is that N2O inactivates cobalamin and can aggravate the clinical picture of patients who already have clinical manifestations of cobalamin deficiency. The elderly are known to have an increased risk of developing mental changes after surgery and it may be that sometimes these result from aggravation of subclinical cobalamin deficiency. The study recruits people over the age of 60 years who are undergoing clinically indicated elective surgery requiring general anesthesia for more than 1 hour. Patients meeting exclusion and inclusion criteria are randomized to receive either a standard anesthetic regimen that includes N2O or a nearly identical one without N2O. Before surgery and 2 weeks and 4 weeks after surgery, each patient undergoes (1) a broad battery of tests of cognition and mood and (2) blood tests measuring cobalamin, folate and homocysteine-methionine metabolism to determine whether they have any subtle biochemical impairment of cobalamin status. DNA from blood cells is also tested for the presence of common mutations that affect key enzymes in those metabolic pathways. A brief testing for postoperative delirium is also done 2 hours after surgery. The patient subgroups' are analyzed for neuropsychologic changes over time, using the preoperative test as the baseline for all comparisons, and associations of those changes with metabolic, genetic, demographic and clinical data. The primary question is what effect routine N2O exposure has on the latter compared with non-N2O anesthesia in elderly people who either have or do not have subclinical cobalamin deficiency. It will help answer whether or not the combination can help explain the increased risk of cognitive problems after surgery in elderly patients, and by extension whether preoperative cobalamin testing and treatment may be indicated in the elderly. It will also test whether genetic predisposition affects the described problems.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2003
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2003
CompletedFirst Submitted
Initial submission to the registry
September 13, 2005
CompletedFirst Posted
Study publicly available on registry
September 21, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedAugust 8, 2022
November 1, 2012
4.9 years
September 13, 2005
August 3, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
neuropsychologic performance changes
4 weeks
Secondary Outcomes (1)
metabolic changes
4 weeks
Study Arms (2)
General anesthesia with nitrous oxide
EXPERIMENTALGeneral anesthesia without nitrous oxide
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- age \>60 years; elective surgery requiring general anesthesia for an hour or more; English speaker
You may not qualify if:
- Surgery involving CNS, blood supply to head, or cardiovascular system; preexisting dementia, psychosis or stroke; contraindication to any of the planned anesthetic agents; exposure to nitrous oxide in past 6 months; clinical status other than ASA class 1 or 2; bronchospastic or chronic obstructive lung disease; use of cobalamin injections in past 6 months; serum creatinine \>1.8 mg.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
New York Methodist Hospital
Brooklyn, New York, 11215, United States
WeillMedical College of Cornell University
New York, New York, 10021, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ralph Carmel, MD
New York Presbyterian Brooklyn Methodist Hospital
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2005
First Posted
September 21, 2005
Study Start
September 1, 2003
Primary Completion
August 1, 2008
Study Completion
August 1, 2008
Last Updated
August 8, 2022
Record last verified: 2012-11