Preoperative Vitamin B12 and Folic Acid on POCD in Elderly Non-cardiac Surgical Patients

NCT03485404 | Terminated DMC

• 1 other identifier: KY20172057-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

Brief Summary

This study will recruit patients more than 65 years old eligible for non-cardiac surgery. Patients who participate will take either vitamin B12 and folic acid supplementation or placebo for 7 days before surgery. Neuropsychological test battery (NPB) will be tested before intervention and at discharge for determination of Post operative cognitive dysfunction (POCD). Another group of non-surgical elderly participants will also be tested for NPB to account for learning effect in POCD diagnosis. The hypothesis is that preoperative vitamin B12 supplementation will reduce the incidence of POCD in elderly patients undergoing non-cardiac surgery.

Conditions

Post Operative Cognitive Dysfunction

Keywords

POCD; vitamin B12; folic acid

Outcome Measures

Primary Outcomes (1)

• Incidence of POCD at discharge or 7 days after operation

  POCD incidence is defined as two or more test of the neuropsychological battery declined as compared to preoperative baseline.

  at discharge or at 7 days after operation if the patient is not discharged by then

Secondary Outcomes (5)

• Activity daily living score

  3 months after operation

• Serum level of vitamin B12, folic acid and homocysteine

  Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1

• Serum level of cystatin C and myeloid differentiation protein 2

  Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1

• Length of hospital stay

  Date from hospital admission to hospital discharge. This length is usually around 7-14 days. It may be longer if the patient have one or more complications. The length will be documented at patient discharge, up to 100 weeks.

• Incidence of in hospital complications

  From date of hospital admission to date of hospital discharge after surgery. Usually 7-14 days, assessed up to 100 weeks.

Study Arms (3)

VB12+FA

EXPERIMENTAL

Patients will receive oral supplementation of 0.5mg methylcobalamin, 3/day and 5 mg folic acid, 1/day for 7 days before non-cardiac surgery.

Drug: methylcobalamin; Drug: Folic Acid; Procedure: non-cardiac surgery; Behavioral: NPB test

Placebo

PLACEBO COMPARATOR

Patients with receive oral tablets of placebo for folic acid 1/d and placebo for methylcobalamin 3/d, which look exactly like the interventional drugs as oral supplementation for 7 days before non-cardiac surgery.

Other: Placebo for methylcobalamin; Other: Placebo for folic acid; Procedure: non-cardiac surgery; Behavioral: NPB test

Non-surgical controls

OTHER

Age and sex-matched community elderly people are included for two sessions of NPB test evaluation for calculation of POCD incidence as normal control to in Z value calculation of POCd incidence to rule out learning effect.

Behavioral: NPB test

Interventions

methylcobalamin DRUG

methylcobalamin tablets, 0.5mg/tablet, 3 tablets/day.

Also known as: vitamin B12, VB12

VB12+FA

Folic Acid DRUG

folic acid tablets, 5mg/tablet, 1 tablet/day

Also known as: vitamin B9

VB12+FA

Placebo for methylcobalamin OTHER

orange tablets that looks exactly like methylcobalamin

Placebo

Placebo for folic acid OTHER

yellow tablets that looks exactly like folic acid

Placebo

non-cardiac surgery PROCEDURE

patients elective for non-cardiac surgery will undergo scheduled surgery after 7 days of intervention

Placebo; VB12+FA

NPB test BEHAVIORAL

participants will accept Mini-Mental State Examination (MMSE), Patient Health Questionnaire (PHQ-9), ADL, and NPB test before intervention, and NPB by discharge or similar time intermittent after the first assessment for non-surgical controls. Also ADL will be tested again through telephone interview at 3 months after discharge.

Also known as: neuropsychological battery tests, assessment of POCD

Non-surgical controls; Placebo; VB12+FA

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• \. Age equals or over 65
• \. Scheduled for spinal or joint replacement surgery under general anesthesia，estimated surgery time over 2h.
• \. Signed written informed consent obtained
• \. Non-surgical Controls are age and sex - matched community elderly residents.

You may not qualify if:

• \. Disease of the central nervous system that impairs cognitive function, including all kinds of dementia, and depression
• \. MMSE score \< 24
• \. Received education for less than 5 years
• \. Currently taking sedative or antidepressant drugs
• \. Has taken vitamin B12, folic acid or their derivatives (methycobalamin, cobalamin, tetrahydrofolic acid, etc.) within 6 months.
• \. Has accepted cardiac or neurological surgery within one year.
• \. Was admitted for other clinical trials within 3 month
• \. Patients that regularly taking drugs that affect vitamin B absorption, including colchicine, neomycin, salicylate.
• \. Has severe visual or auditory problems
• \. Alcohol or drug dependent (alcohol dependent: drank more than 100 mL of Chinese liqueur with alcohol concentration over 40% everyday for the past 3 months).
• \. Patients that are already admitted for this study can not be admitted the second time, no matter the cause of surgery

Sponsors & Collaborators

• Xijing Hospital: lead
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Tang-Du Hospital: collaborator
• Shaanxi Provincial People's Hospital: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Anhui Provincial Hospital: collaborator
• Shanghai 10th People's Hospital: collaborator

Study Sites (13)

Anhui Provincial Hospital

Hefei, Anhui, 230001, China

Location

Shenzhen University General Hospital

Shenzhen, Guangdong, China

Location

The Third Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Location

Henan Provincial People's Hospital

Zhengzhou, Henan, China

Location

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710032, China

Location

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, 710032, China

Location

Tangdu Hospital

Xi'an, Shaanxi, 710032, China

Location

Xijing Hospital

Xi'an, Shaanxi, 710032, China

Location

Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

Location

Shanghai 10th People's Hospital

Shanghai, 200072, China

Location

Shanghai Changzheng Hospital

Shanghai, China

Location

Shanghai Forth People's Hospital

Shanghai, China

Location

MeSH Terms

Interventions

mecobalamin; Vitamin B 12; Folic Acid

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring

Study Officials

• Lize Xiong, M.D., Ph.D.

  Xijing Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Central randomization. Groups are marked as A and B with no participants, care provider, investigator and outcome assessors know which group is the drug and which is the placebo. Placebo are made as tablets that mimics the color, shape and size of the drugs.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: April 2, 2018
• Study Start: January 10, 2019
• Primary Completion: July 29, 2021
• Study Completion: July 29, 2021
• Last Updated: August 4, 2021

Record last verified: 2021-07

Locations

CN (13)