Post Operative Cognitive DysfunctionB12-POCDNCT03485404
Preoperative Vitamin B12 and Folic Acid on POCD in Elderly Non-cardiac Surgical Patients
A study testing methylcobalamin, Folic Acid and non-cardiac surgery in people with Post Operative Cognitive Dysfunction, run by Xijing Hospital at 13 sites in China.
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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Post Operative Cognitive Dysfunction
- What is being tested?
- methylcobalamin, Folic Acid and non-cardiac surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 13 sitesChina
- Study dates
- 10 Jan 2019to 29 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
China13 sites
Anhui Provincial Hospital
Hefei, Anhui, 230001
Shandong Provincial Qianfoshan Hospital
Jinan, Shandong
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008
Shanghai 10th People's Hospital
Shanghai, 200072
Shanghai Changzheng Hospital
Shanghai
Shanghai Forth People's Hospital
Shanghai
Shenzhen University General Hospital
Shenzhen, Guangdong
The Third Hospital of Hebei Medical University
Shijiazhuang, Hebei
First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710032
Shaanxi Provincial People's Hospital
Xi'an, Shaanxi, 710032
Tangdu Hospital
Xi'an, Shaanxi, 710032
Xijing Hospital
Xi'an, Shaanxi, 710032
Henan Provincial People's Hospital
Zhengzhou, Henan
About this study
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
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.
Read the 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.
- Conditions
- Post Operative Cognitive Dysfunction
- Being tested
- methylcobalamin, Folic Acid, Placebo for methylcobalamin, Placebo for folic acid, non-cardiac surgery
- Keywords
- POCD, vitamin B12, folic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylcobalaminDrug
Also called vitamin B12, VB12
methylcobalamin tablets, 0.5mg/tablet, 3 tablets/day.
Folic AcidDrug
Also called vitamin B9
folic acid tablets, 5mg/tablet, 1 tablet/day
Placebo for methylcobalaminOther
orange tablets that looks exactly like methylcobalamin
Placebo for folic acidOther
yellow tablets that looks exactly like folic acid
non-cardiac surgeryProcedure or surgery
patients elective for non-cardiac surgery will undergo scheduled surgery after 7 days of intervention
NPB testBehavioural
Also called neuropsychological battery tests, assessment of POCD
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Behavioral: NPB test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at discharge or at 7 days after operation if the patient is not discharged by then
Secondary outcomes (5)
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.）
Measured: 3 months after operation
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.
Measured: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
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.
Measured: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
Length of hospital stay
to see if our intervention could reduce the total days of patient spent in hospital,
Measured: 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
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.
Measured: From date of hospital admission to date of hospital discharge after surgery. Usually 7-14 days, assessed up to 100 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2018
- Study start10 Jan 2019
- Primary completion29 Jul 2021
- Study completion29 Jul 2021
Why it stopped: Due to slow recruiment. Only 40 patients were recruited in four years.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Operative Cognitive DysfunctionStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- First Affiliated Hospital Xi'an Jiaotong University, Tang-Du Hospital, Shaanxi Provincial People's Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Anhui Provincial Hospital, Shanghai 10th People's Hospital
- Responsible party
- Principal investigator, Lize Xiong, Xijing Hospital
- Investigators
- Lize Xiong, M.D., Ph.D., Study chair, Xijing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03485404
- Sponsor's protocol ID
- KY20172057-1
- Acronym
- B12-POCD
- Status last verified
- Jul 2021
- First submitted
- 7 Mar 2018
- Last updated
- 4 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03485404
- Acronym / sponsor ID
- B12-POCD / KY20172057-1
- Conditions
- Post Operative Cognitive Dysfunction
- Keywords
- POCD, vitamin B12, folic acid
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to slow recruiment. Only 40 patients were recruited in four years.
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Collaborators
- First Affiliated Hospital Xi'an Jiaotong University, Tang-Du Hospital, Shaanxi Provincial People's Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Anhui Provincial Hospital, Shanghai 10th People's Hospital
- Study start
- 10 Jan 2019 (actual)
- Primary completion
- 29 Jul 2021 (actual)
- Study completion
- 29 Jul 2021 (actual)
- First posted
- 2 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VB12+FA | Experimental | Drug: methylcobalamin, Drug: Folic Acid, Procedure: non-cardiac surgery, Behavioral: NPB testPatients will receive oral supplementation of 0.5mg methylcobalamin, 3/day and 5 mg folic acid, 1/day for 7 days before non-cardiac surgery. |
| Placebo | Placebo comparator | Other: Placebo for methylcobalamin, Other: Placebo for folic acid, Procedure: non-cardiac surgery, Behavioral: NPB testPatients 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. |
| Non-surgical controls | Other | Behavioral: NPB testAge 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methylcobalaminAlso: vitamin B12, VB12methylcobalamin tablets, 0.5mg/tablet, 3 tablets/day. | Drug | VB12+FA |
| Folic AcidAlso: vitamin B9folic acid tablets, 5mg/tablet, 1 tablet/day | Drug | VB12+FA |
| Placebo for methylcobalaminorange tablets that looks exactly like methylcobalamin | Other | Placebo |
| Placebo for folic acidyellow tablets that looks exactly like folic acid | Other | Placebo |
| non-cardiac surgerypatients elective for non-cardiac surgery will undergo scheduled surgery after 7 days of intervention | Procedure or surgery | Placebo, VB12+FA |
| NPB testAlso: neuropsychological battery tests, assessment of POCDparticipants 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. | Behavioural | Non-surgical controls, Placebo, VB12+FA |
Primary outcome
Incidence of POCD at discharge or 7 days after operation
Time frame: at discharge or at 7 days after operation if the patient is not discharged by then
POCD incidence is defined as two or more test of the neuropsychological battery declined as compared to preoperative baseline.
5 secondary outcomes
Activity daily living score
Time frame: 3 months after operation
Serum level of vitamin B12, folic acid and homocysteine
Time frame: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
Serum level of cystatin C and myeloid differentiation protein 2
Time frame: Immediately before anesthesia, immediately after surgery and on the morning of postoperative day 1
Length of hospital stay
Time frame: 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
Time frame: From date of hospital admission to date of hospital discharge after surgery. Usually 7-14 days, assessed up to 100 weeks.
Results and safety
The study was stopped early (reason given: Due to slow recruiment. Only 40 patients were recruited in four years.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lize Xiong, M.D., Ph.D. study chair
Xijing Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing methylcobalamin, Folic Acid and non-cardiac surgery in people with Post Operative Cognitive Dysfunction, run by Xijing Hospital at 13 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Due to slow recruiment. Only 40 patients were recruited in four years.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of POCD at discharge or 7 days after operation (time frame: at discharge or at 7 days after operation if the patient is not discharged by then). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2021.