Clinical trial NCT03485404: Preoperative Vitamin B12 and Folic Acid on POCD in Elderly Non-cardiac Surgical Patients
Official title: Effect of Preoperative Vitamin B12 on Post Operative Cognitive Dysfunction in Elderly Patients Undergoing Non-cardiac Surgery: A Multi-Center, Prospective, Randomized, Double-blinded, Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Post Operative Cognitive Dysfunction
Keywords: POCD
vitamin B12
folic acid
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital Xi'an Jiaotong University
name: Tang-Du Hospital
name: Shaanxi Provincial People's Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Anhui Provincial Hospital
name: Shanghai 10th People's Hospital
First posted: 2018-04-02
Enrollment: 40
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: Vitamin B12 has long been suggested to have neural nutrient effect and widely used in clinical settings for patients with peripheral nerve injury as well as complementary medicine for patients with CNS disorders, including cognitive dysfunction. Evidences showed that, although no significant improvement in cognitive function was observed in healthy elderly after vitamin B12 supplementation, some studies suggested that patients with pre-existing CNS disorder may benefit from Vitamin B12. Post operational cognitive dysfunction (POCD) is severe, and long-lasting complication that affects as high as 53% of patients in high risk surgeries. Age is an independent risk factor for POCD. Researches have shown that serum vitamin B12 level decrease with age, and methylcobalamin (active form of Vitamin B12) content in the frontal cortex of aged patients are lower than that of younger patients. However, there are no report on effect of preemptive supplementation of vitamin B12 on POCD incidence. Therefore, the current research is aimed to explore the preoperative methylcobalamin supplementation (500 mg, 3/day for 7 days before surgery) on incidence of POCD. Folic acid supplementation is a common companion for vitamin B12 treatment in clinical settings because they are in the same methionine cycle, increase of one may result in deficiency of another. So we added 5 mg, 1/day of folic acid with methylcobalamin in the treatment group.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 1. Disease of the central nervous system that impairs cognitive function, including all kinds of dementia, and depression
* 2. MMSE score \< 24
* 3. Received education for less than 5 years
* 4. Currently taking sedative or antidepressant drugs
* 5. Has taken vitamin B12, folic acid or their derivatives (methycobalamin, cobalamin, tetrahydrofolic acid, etc.) within 6 months.
* 6. Has accepted cardiac or neurological surgery within one year.
* 7. Was admitted for other clinical trials within 3 month
* 8. Patients that regularly taking drugs that affect vitamin B absorption, including colchicine, neomycin, salicylate.
* 9. Has severe visual or auditory problems
* 10. 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).
* 11. Patients that are already admitted for this study can not be admitted the second time, no matter the cause of surgery

Primary outcomes:
measure: Incidence of POCD at discharge or 7 days after operation
timeFrame: at discharge or at 7 days after operation if the patient is not discharged by then
Secondary outcomes:
measure: Activity daily living score
timeFrame: 3 months after operation
measure: Serum level of vitamin B12, folic acid and homocysteine
timeFrame: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
measure: Serum level of cystatin C and myeloid differentiation protein 2
timeFrame: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
measure: Length of hospital stay
timeFrame: 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.
measure: Incidence of in hospital complications
timeFrame: From date of hospital admission to date of hospital discharge after surgery. Usually 7-14 days, assessed up to 100 weeks.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Shenzhen
country: China
facility: Shenzhen University General Hospital
state: Guangdong
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai 10th People's Hospital
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Forth People's Hospital
Study officials:
affiliation: Xijing Hospital
name: Lize Xiong, M.D., Ph.D.
role: STUDY_CHAIR
References: