Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia

NCT ID: NCT00901394

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-01-31

Brief Summary

The goal of this study is to find out if giving intravenous B-vitamins before general anesthesia with nitrous oxide prevents the increase in homocysteine, a metabolite that has been linked to cardiovascular complications.

Detailed Description

Patients will be randomized into the following arms:

• Arm A: patients will receive N2O (60% N2O/40% O2) in an open-label fashion during surgery and vitamin supplementation (vitamin B12, 1 mg, and folate, 5 mg) before surgery.
• Arm B: patients will receive N2O 60% N2O/40% O2) in an open-label fashion during surgery and placebo before and after surgery.
• Arm C: patients will not receive N2O, vitamin supplementation, or placebo during/before surgery. Patients in this arm will not be randomized.

Patients will have blood drawn (total of 1-2 teaspoons over 3 days). We will take these samples before their surgery, when their surgery is completed, and in the morning of post-operative day 1. We will be checking their troponin I and troponin T, homocysteine, Vitamin B12, and folate levels. We will also perform a 12-lead EKG. Before and after surgery for patients in Arm A or B, will receive either vitamin B12 (1 mg) and folic acid (5 mg) (or placebo) added to their IV infusion. We also plan to use a non-invasive test known as a nerve conduction study to measure the function of their nerve system. Briefly, 2 small electrodes are attached to their skin over a nerve and, like an EKG, faint electrical pulses are generated and recorded. A typical nerve conduction measurement lasts about 10 minutes.

After the patients surgery we will do genetic testing of MTHFR genotype.

All study samples have been collected.

Of note: there were no secondary outcomes.

Conditions

Cardiovascular Abnormalities

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment 1

B12-Folic acid, nitrous oxide

Group Type: EXPERIMENTAL

B12-Folic Acid, nitrous oxide

Intervention Type: DRUG

IV vitamin B12 (cyanocobalamin) 1 mg, single administration over 30 min.

IV folic acid, 5 mg, single administration over 30 min.

Both diluted in 250 ml normal saline.

Nitrous oxide (NO) and placebo

Intervention Type: DRUG

60% nitrous oxide anesthesia plus saline

Treatment 2

Nitrous oxide (NO) and placebo

Group Type: ACTIVE_COMPARATOR

Nitrous oxide (NO) and placebo

Intervention Type: DRUG

60% nitrous oxide anesthesia plus saline

Placebo

Intervention Type: OTHER

Saline

Control group

oxygen nitrogen

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Saline

oxygen nitrogen

Intervention Type: OTHER

60% air and oxygen mix.

Interventions

B12-Folic Acid, nitrous oxide

IV vitamin B12 (cyanocobalamin) 1 mg, single administration over 30 min.

IV folic acid, 5 mg, single administration over 30 min.

Both diluted in 250 ml normal saline.

Intervention Type: DRUG

Nitrous oxide (NO) and placebo

60% nitrous oxide anesthesia plus saline

Intervention Type: DRUG

Placebo

Saline

Intervention Type: OTHER

oxygen nitrogen

60% air and oxygen mix.

Intervention Type: OTHER

Other Intervention Names

b supplements; nitrous oxide; saline; air

Eligibility Criteria

Inclusion Criteria

• Adult patients scheduled for elective surgery with expected duration > 2 hours
• Healthy patients undergoing moderate surgery where the use of N2O is unproblematic

Exclusion Criteria

• Contraindication against N2O (pneumothorax, mechanical bowel obstruction, middle ear occlusion, laparoscopic surgery, raised intracranial pressure)
• Patients requiring supplemental oxygen
• Urgent or emergent surgery
• Patients with vitamin B12 or folate deficiency or megaloblastic anemia
• Patients with seizure disorder (epilepsy)
• Allergy or hypersensitivity against IV cobalamin or folate
• Patients with Leber's disease (hereditary optic nerve atrophy)
• Patients taking supplemental vitamin B12 or folate

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Anesthesia Education and Research

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Nagele, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Barnes Jewish Hospital

St Louis, Missouri, United States

Countries

United States

References

Nagele P, Zeugswetter B, Wiener C, Burger H, Hupfl M, Mittlbock M, Fodinger M. Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia. Anesthesiology. 2008 Jul;109(1):36-43. doi: 10.1097/ALN.0b013e318178820b.

Reference Type: BACKGROUND

PMID: 18580170 (View on PubMed)

Nagele P, Zeugswetter B, Eberle C, Hupfl M, Mittlbock M, Fodinger M. A common gene variant in methionine synthase reductase is not associated with peak homocysteine concentrations after nitrous oxide anesthesia. Pharmacogenet Genomics. 2009 May;19(5):325-9. doi: 10.1097/FPC.0b013e328328d54c.

Reference Type: BACKGROUND

PMID: 19339913 (View on PubMed)

Myles PS, Chan MT, Kaye DM, McIlroy DR, Lau CW, Symons JA, Chen S. Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function. Anesthesiology. 2008 Oct;109(4):657-63. doi: 10.1097/ALN.0b013e31818629db.

Reference Type: BACKGROUND

PMID: 18813045 (View on PubMed)

Other Identifiers

09-0074

Identifier Type: -

Identifier Source: org_study_id