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

Post Operative Cognitive Dysfunction Clinical Trial

— B12-POCD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03485404
• Other study ID #: KY20172057-1
• Status: Terminated
• Phase: N/A
• Start date: January 10, 2019
• Est. completion date: July 29, 2021

Study information

• Verified date: July 2021
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: July 29, 2021
• Est. primary completion date: July 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Post Operative Cognitive Dysfunction

Intervention

Drug:
• methylcobalamin
methylcobalamin tablets, 0.5mg/tablet, 3 tablets/day.
• Folic Acid
folic acid tablets, 5mg/tablet, 1 tablet/day

Other:
• Placebo for methylcobalamin
orange tablets that looks exactly like methylcobalamin
• Placebo for folic acid
yellow tablets that looks exactly like folic acid

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

Behavioral:
• NPB test
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.

Locations

Country	Name	City	State
China	Anhui Provincial Hospital	Hefei	Anhui
China	Shandong Provincial Qianfoshan Hospital	Jinan	Shandong
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Shanghai 10th People's Hospital	Shanghai
China	Shanghai Changzheng Hospital	Shanghai
China	Shanghai Forth People's Hospital	Shanghai
China	Shenzhen University General Hospital	Shenzhen	Guangdong
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Shaanxi Provincial People's Hospital	Xi'an	Shaanxi
China	Tangdu Hospital	Xi'an	Shaanxi
China	Xijing Hospital	Xi'an	Shaanxi
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (7)

Lead Sponsor	Collaborator
Xijing Hospital	Anhui Provincial Hospital, First Affiliated Hospital Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Shanghai 10th People's Hospital, Tang-Du Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Activity daily living score	Telephone interview of activity daily living score (14 items, 1-4 points per item, ranging 14-56 points with 56 being the worst-unable to complete any task of everyday living.)	3 months after operation
Secondary	Serum level of vitamin B12, folic acid and homocysteine	Ten ml of venous blood will be collected from patients to test the differences of serum levels of vitamin B12, folic acid and homocysteine to show the effect of preoperative supplementation and surgery stimulation on these parameters.	Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
Secondary	Serum level of cystatin C and myeloid differentiation protein 2	Ten ml of venous blood will be collected from patients to test the differences of serum levels of cystatin C and myeloid differentiation protein 2.	Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
Secondary	Length of hospital stay	to see if our intervention could reduce the total days of patient spent in hospital,	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.
Secondary	Incidence of in hospital complications	Overall rate of perioperative major complications including hemorrhage, deep vein thrombosis, cardiovascular complications, respiratory complications, acute kidney injury, infection or second operative needed, during patient's hospital stay.	From date of hospital admission to date of hospital discharge after surgery. Usually 7-14 days, assessed up to 100 weeks.