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Interaction of Cobalamin Status With Nitrous Oxide in Relation to Postoperative Cognitive Changes in the Elderly

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00212147
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : August 8, 2022
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

Condition or disease Intervention/treatment Phase
Avitaminosis Delirium, Dementia, Amnestic, Cognitive Disorders Drug: General anesthesia with nitrous oxide Drug: General anesthesia without nitrous oxide Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 444 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: Subtle Disturbances of Cobalamin Status
Study Start Date : September 2003
Actual Primary Completion Date : August 2008
Actual Study Completion Date : August 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: General anesthesia with nitrous oxide Drug: General anesthesia with nitrous oxide
Active Comparator: General anesthesia without nitrous oxide Drug: General anesthesia without nitrous oxide

Primary Outcome Measures :
  1. neuropsychologic performance changes [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. metabolic changes [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • age >60 years; elective surgery requiring general anesthesia for an hour or more; English speaker

Exclusion Criteria:

  • 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.

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 identifier (NCT number): NCT00212147

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United States, New York
New York Methodist Hospital
Brooklyn, New York, United States, 11215
WeillMedical College of Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Ralph Carmel, MD New York Presbyterian Brooklyn Methodist Hospital
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00212147    
Other Study ID Numbers: DK32640 (completed)
R01DK032640 ( U.S. NIH Grant/Contract )
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: August 8, 2022
Last Verified: November 2012
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Additional relevant MeSH terms:
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Cognition Disorders
Neurocognitive Disorders
Nervous System Diseases
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Deficiency Diseases
Nutrition Disorders
Nitrous Oxide
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Inhalation
Anesthetics, General
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents