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

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00212147
First received: September 13, 2005
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

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 Intervention
Avitaminosis
Delirium, Dementia, Amnestic, Cognitive Disorders
Drug: general anesthesia

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Subtle Disturbances of Cobalamin Status

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • neuropsychologic performance changes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • metabolic changes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 444
Study Start Date: September 2003
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: I
General anesthesia that includes nitrous oxide
Drug: general anesthesia
anesthesia regimen with nitrous oxide or without nitrous oxide
Active Comparator: II
General anesthesia not including nitrous oxide
Drug: general anesthesia
anesthesia regimen with nitrous oxide or without nitrous oxide

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00212147

Locations
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
Investigators
Principal Investigator: Ralph Carmel, MD New York Methodist Hospital
  More Information

No publications provided

Responsible Party: Ralph Carmel - Principal Investigator, New York Methodist Hospital
ClinicalTrials.gov Identifier: NCT00212147     History of Changes
Other Study ID Numbers: DK32640 (completed)
Study First Received: September 13, 2005
Last Updated: November 6, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
cobalamin
anesthesia
cognition

Additional relevant MeSH terms:
Deficiency Diseases
Avitaminosis
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Malnutrition
Mental Disorders
Nutrition Disorders
Anesthetics
Nitrous Oxide
Analgesics
Analgesics, Non-Narcotic
Anesthetics, General
Anesthetics, Inhalation
Central Nervous System Agents
Central Nervous System Depressants
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014