Vitamins in Nitrous Oxide Study (VINO)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Washington University School of Medicine.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Foundation for Anesthesia Education and Research
Information provided by (Responsible Party):
Peter Nagele, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00655980
First received: April 4, 2008
Last updated: April 11, 2012
Last verified: April 2012
  Purpose

In this study, we want to find out if laughing gas (nitrous oxide) leads to a higher rate of cardiac complications after surgery in patients with a specific genetic profile (mutations in the MTHFR gene) and if this risk can be prevented by giving patients vitamin B12 and folate during surgery.


Condition Intervention
Major Surgery
Coronary Artery Disease
Drug: Vitamin B12 and folic acid

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Myocardial ischemia [ Time Frame: first 3 postoperative days ] [ Designated as safety issue: No ]
    Measured by serial troponin and ECG


Secondary Outcome Measures:
  • Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI) [ Time Frame: 30 day postoperative ] [ Designated as safety issue: No ]

Estimated Enrollment: 625
Study Start Date: February 2008
Estimated Study Completion Date: July 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients receive N2O during surgery and B-vitamin before and after anesthesia
Drug: Vitamin B12 and folic acid
1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
Placebo Comparator: 2
Patients receive N2O during surgery but receive NO B-vitamins but a "placebo" ( normal saline 100ml)
Drug: Vitamin B12 and folic acid
1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
No Intervention: 3
Patients receive no N2O and no B-vitamins. Patients in this control group will be concurrently enrolled, not randomized, but will meet the identical inclusion and exclusion criteria

Detailed Description:

Background and significance: Recent studies have shown that nitrous oxide (N2O) anesthesia may be associated with an increased risk of adverse cardiovascular outcomes. It is well-known that N2O inhibits vitamin B12-dependent enzymes and as a result increases plasma homocysteine concentrations. Homocysteine has been identified as risk factor for cardiovascular disease. Therefore elevations in homocysteine after N2O may be a causative factor in N2O toxicity. In a previous investigation, we found that patients who carry a homozygous mutation in the MTHFR gene develop higher homocysteine levels after N2O anesthesia than non-carriers. These patients might be at higher risk for adverse cardiac outcomes from N2O. Thus, there may be a pharmacogenetic mechanism to account for the adverse cardiac outcomes from N2O. Moreover, prevention of N2O-increased homocysteine concentrations in these high risk patients by perioperative vitamin B12 and folate supplementation might decrease the incidence of adverse cardiac outcomes.

Hypothesis: Patients carrying a homozygous MTHFR 677C>T or 1298 A>C variant allele will have a higher incidence rate of postoperative myocardial ischemia after N2O anesthesia [detected by serial TnI measurements] due to elevated homocysteine levels than normal "wild-type" non-carriers, and that the incidence rate will be reduced if they receive perioperative vitamin B12/folate supplementation.

Primary outcome: Myocardial ischemia in the first 72 hours after surgery (measured by serial troponin and ECGs).

Secondary outcome: Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI)

Design: Randomized controlled trial. 500 patients will receive N2O during surgery and will be randomized to receive B-vitamins or placebo. 125 patients will receive no N2O and no B-vitamins (control arm). Mendelian randomization of MTHFR genotype.

Intervention: IV vitamin B12 (1 mg) and folate (5 mg) pre- and postoperatively

Study setting: Barnes-Jewish-Hospital, St. Louis, MO

Patients: Patients scheduled for major surgery with or at risk for coronary artery disease

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients; age >18 yrs, ASA III-IV
  • Previously diagnosed coronary artery disease or at risk for coronary artery disease
  • Scheduled for major surgery (>2 hrs)

Exclusion Criteria:

  • Patients not expected to live past 24 hours (ASA 5)
  • Patients with significant pulmonary disease requiring supplemental oxygen
  • Patients taking supplemental vitamin B12 or folate
  • Contraindication against N2O (pneumothorax, mechanical bowel obstruction, middle ear occlusion, laparoscopic surgery, raised intracranial pressure)
  • Hypersensitivity to cobalamins
  • Leber's disease (hereditary optic nerve atrophy) [vitamin B12 interaction]
  • Seizure disorder [folate interference]
  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: NCT00655980

Locations
United States, Missouri
Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Foundation for Anesthesia Education and Research
Investigators
Principal Investigator: Peter Nagele, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Peter Nagele, Assistant Professor of Anesthesiology, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00655980     History of Changes
Other Study ID Numbers: HSC 07-0592
Study First Received: April 4, 2008
Last Updated: April 11, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Folic Acid
Hydroxocobalamin
Vitamin B Complex
Vitamin B 12
Vitamins
Nitrous Oxide
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014