Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium (MAPOCD)
Primary Purpose
Prostate Cancer, Carcinoma of the Rectum, Colon Cancer
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Minocycline
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Prostate Cancer focused on measuring Minocycline, Postoperative cognitive dysfunction, Postoperative delirium
Eligibility Criteria
For the placebo and minocycline group;
Inclusion Criteria:
- Elder than 65 years old
- Speak Chinese Mandarin
- Those who will undergo major general surgery like colorectal cancer excision, major urinary surgery like radical prostatectomy and radical nephrectomy
- Signed the inform consent
- American Society of Anesthesiologists classification I to III
Exclusion Criteria:
- Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;
- Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;
- Severe audition or vision disorder;
- Unwillingness to comply with the protocol or procedures.
- Cannot communicated with Chinese Mandarin
- With severe skin disease
- Serious heart or liver or renal insufficiency patients
- Had surgery in the past 30 days
- Allergy to tetracycline or minocycline
For the health volunteers;
Inclusion Criteria:
- Elder than 65 years old
- Speak Chinese Mandarin
- Signed the inform consent
- No major disease health people
Exclusion Criteria:
- Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;
- Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;
- Severe audition or vision disorder;
- Unwillingness to comply with the protocol or procedures.
- Cannot communicated with Chinese Mandarin
- Drug abuse, alcoholism
- Serious heart or liver or renal insufficiency patients
- Had surgery in the past 30 days
- Plan to undergo surgery in the following 3 months.
Sites / Locations
- ScalesRecruiting
- Shanghai Pudong Hospital
- Shanghai Pudong New Area Dongming Community Health Care CenterRecruiting
- Shanghai Pudong New Area people's HopsitalRecruiting
- Shanghai Tenth HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
No Intervention
Arm Label
Placebo
Minocycline
Volunteers
Arm Description
Placebo administered before surgery
Minocycline was administrated before surgery
Health people for calculate the incidence of POCD
Outcomes
Primary Outcome Measures
POCD incidence 7 days (or before leaving hospital) after surgery
POD incidence
Secondary Outcome Measures
POCD incidence 2 months after surgery
Full Information
NCT ID
NCT02928692
First Posted
October 5, 2016
Last Updated
January 25, 2020
Sponsor
RenJi Hospital
Collaborators
Shanghai 10th People's Hospital, Pudong New Area People's Hospital, Shanghai Pudong Hospital, Shanghai Pudong New Aera Dongming Community Health Care Center
1. Study Identification
Unique Protocol Identification Number
NCT02928692
Brief Title
Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium
Acronym
MAPOCD
Official Title
Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium: A Multicenter, Randomized, Double-Blind Clinical Trail
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2016 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
RenJi Hospital
Collaborators
Shanghai 10th People's Hospital, Pudong New Area People's Hospital, Shanghai Pudong Hospital, Shanghai Pudong New Aera Dongming Community Health Care Center
4. Oversight
5. Study Description
Brief Summary
Postoperative cognitive dysfunction (POCD) and postoperative delirium occurs mainly in aged patients. POCD and POD may increase the mortality and morbidity. However, the mechanism of POCD is not clear yet and no effective therapy method was proved. According to previous study, the neuroinflammation is the main reason both for POCD and POD. Minocycline is a tetracycline derivative. Due to it's lipophilic structure, it is easy to pass through blood brain barrier and attenuate neuroinflammation. It's neuroprotective effects has been proven in many experimental animal models such as Alzheimer's disease, Huntington's disease and Parkinson's syndrome. In present study, the investigators hypothesized that minocycline would attenuate the incidence of POCD and POD in the aged patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Carcinoma of the Rectum, Colon Cancer, Renal Carcinoma
Keywords
Minocycline, Postoperative cognitive dysfunction, Postoperative delirium
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
750 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered before surgery
Arm Title
Minocycline
Arm Type
Experimental
Arm Description
Minocycline was administrated before surgery
Arm Title
Volunteers
Arm Type
No Intervention
Arm Description
Health people for calculate the incidence of POCD
Intervention Type
Drug
Intervention Name(s)
Minocycline
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
POCD incidence 7 days (or before leaving hospital) after surgery
Time Frame
7 days (or before leaving hospital)
Title
POD incidence
Time Frame
1 to 5 days after surgery
Secondary Outcome Measure Information:
Title
POCD incidence 2 months after surgery
Time Frame
2 months after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
For the placebo and minocycline group;
Inclusion Criteria:
Elder than 65 years old
Speak Chinese Mandarin
Those who will undergo major general surgery like colorectal cancer excision, major urinary surgery like radical prostatectomy and radical nephrectomy
Signed the inform consent
American Society of Anesthesiologists classification I to III
Exclusion Criteria:
Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;
Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;
Severe audition or vision disorder;
Unwillingness to comply with the protocol or procedures.
Cannot communicated with Chinese Mandarin
With severe skin disease
Serious heart or liver or renal insufficiency patients
Had surgery in the past 30 days
Allergy to tetracycline or minocycline
For the health volunteers;
Inclusion Criteria:
Elder than 65 years old
Speak Chinese Mandarin
Signed the inform consent
No major disease health people
Exclusion Criteria:
Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;
Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;
Severe audition or vision disorder;
Unwillingness to comply with the protocol or procedures.
Cannot communicated with Chinese Mandarin
Drug abuse, alcoholism
Serious heart or liver or renal insufficiency patients
Had surgery in the past 30 days
Plan to undergo surgery in the following 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Diansan Su, Doctor
Phone
18616514088
Email
diansansu@yahoo.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Li, Master Degree Candidate
Phone
15216711923
Email
56428923@qq.com
Facility Information:
Facility Name
Scales
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diansan Su, Dr.
Phone
18616514088
Email
diansansu@yahoo.com
First Name & Middle Initial & Last Name & Degree
Hui Li, M.S.
Phone
15216711923
Email
56428923@qq.com
First Name & Middle Initial & Last Name & Degree
Diansan Su, Dr.
First Name & Middle Initial & Last Name & Degree
Hui Li, M.S.
Facility Name
Shanghai Pudong Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongwei Duan
Phone
189-1879-0035
Facility Name
Shanghai Pudong New Area Dongming Community Health Care Center
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shifen Zhang
Phone
13916517543
Facility Name
Shanghai Pudong New Area people's Hopsital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lizhi Li, M.D.
Phone
139-1768-2738
Email
Fmlilizhi@sina.com.cn
Facility Name
Shanghai Tenth Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shukun Fu, M.D.
Phone
13816343916
Email
shukunfu@163.com
12. IPD Sharing Statement
Citations:
PubMed Identifier
23153950
Citation
Large MC, Reichard C, Williams JT, Chang C, Prasad S, Leung Y, DuBeau C, Bales GT, Steinberg GD. Incidence, risk factors, and complications of postoperative delirium in elderly patients undergoing radical cystectomy. Urology. 2013 Jan;81(1):123-8. doi: 10.1016/j.urology.2012.07.086. Epub 2012 Nov 13.
Results Reference
background
PubMed Identifier
25017770
Citation
Pol RA, van Leeuwen BL, Izaks GJ, Reijnen MM, Visser L, Tielliu IF, Zeebregts CJ. C-reactive protein predicts postoperative delirium following vascular surgery. Ann Vasc Surg. 2014 Nov;28(8):1923-30. doi: 10.1016/j.avsg.2014.07.004. Epub 2014 Jul 10.
Results Reference
background
PubMed Identifier
24384981
Citation
Nadelson MR, Sanders RD, Avidan MS. Perioperative cognitive trajectory in adults. Br J Anaesth. 2014 Mar;112(3):440-51. doi: 10.1093/bja/aet420. Epub 2014 Jan 2.
Results Reference
background
PubMed Identifier
24093540
Citation
Westhoff D, Witlox J, Koenderman L, Kalisvaart KJ, de Jonghe JF, van Stijn MF, Houdijk AP, Hoogland IC, Maclullich AM, van Westerloo DJ, van de Beek D, Eikelenboom P, van Gool WA. Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients. J Neuroinflammation. 2013 Oct 7;10:122. doi: 10.1186/1742-2094-10-122.
Results Reference
background
PubMed Identifier
23040284
Citation
Shim JJ, Leung JM. An update on delirium in the postoperative setting: prevention, diagnosis and management. Best Pract Res Clin Anaesthesiol. 2012 Sep;26(3):327-43. doi: 10.1016/j.bpa.2012.08.003.
Results Reference
background
PubMed Identifier
25516034
Citation
van Meenen LC, van Meenen DM, de Rooij SE, ter Riet G. Risk prediction models for postoperative delirium: a systematic review and meta-analysis. J Am Geriatr Soc. 2014 Dec;62(12):2383-90. doi: 10.1111/jgs.13138.
Results Reference
background
PubMed Identifier
25535170
Citation
American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg. 2015 Feb;220(2):136-48.e1. doi: 10.1016/j.jamcollsurg.2014.10.019. Epub 2014 Nov 14. No abstract available.
Results Reference
background
PubMed Identifier
24890941
Citation
Bellelli G, Mazzola P, Morandi A, Bruni A, Carnevali L, Corsi M, Zatti G, Zambon A, Corrao G, Olofsson B, Gustafson Y, Annoni G. Duration of postoperative delirium is an independent predictor of 6-month mortality in older adults after hip fracture. J Am Geriatr Soc. 2014 Jul;62(7):1335-40. doi: 10.1111/jgs.12885. Epub 2014 Jun 2.
Results Reference
background
PubMed Identifier
19825488
Citation
Ramaiah R, Lam AM. Postoperative cognitive dysfunction in the elderly. Anesthesiol Clin. 2009 Sep;27(3):485-96, table of contents. doi: 10.1016/j.anclin.2009.07.011.
Results Reference
background
PubMed Identifier
19444566
Citation
Sauer AM, Kalkman C, van Dijk D. Postoperative cognitive decline. J Anesth. 2009;23(2):256-9. doi: 10.1007/s00540-009-0744-5. Epub 2009 May 15.
Results Reference
background
PubMed Identifier
9525362
Citation
Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0. Erratum In: Lancet 1998 Jun 6;351(9117):1742.
Results Reference
background
PubMed Identifier
18156878
Citation
Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30. doi: 10.1097/01.anes.0000296071.19434.1e.
Results Reference
background
PubMed Identifier
19225398
Citation
Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS; ISPOCD Group. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009 Mar;110(3):548-55. doi: 10.1097/ALN.0b013e318195b569.
Results Reference
background
PubMed Identifier
23558082
Citation
Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106(1):161-78. doi: 10.1093/bmb/ldt006. Epub 2013 Apr 4.
Results Reference
background
PubMed Identifier
17325501
Citation
Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.
Results Reference
background
PubMed Identifier
21575676
Citation
Fidalgo AR, Cibelli M, White JP, Nagy I, Maze M, Ma D. Systemic inflammation enhances surgery-induced cognitive dysfunction in mice. Neurosci Lett. 2011 Jul 1;498(1):63-6. doi: 10.1016/j.neulet.2011.04.063. Epub 2011 May 6.
Results Reference
background
PubMed Identifier
20818791
Citation
Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360-8. doi: 10.1002/ana.22082.
Results Reference
background
PubMed Identifier
22190370
Citation
Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF, Akassoglou K, Maze M. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011 Dec;70(6):986-995. doi: 10.1002/ana.22664.
Results Reference
background
PubMed Identifier
24162463
Citation
Vacas S, Degos V, Tracey KJ, Maze M. High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow-derived macrophages. Anesthesiology. 2014 May;120(5):1160-7. doi: 10.1097/ALN.0000000000000045.
Results Reference
background
PubMed Identifier
20711073
Citation
Wan Y, Xu J, Meng F, Bao Y, Ge Y, Lobo N, Vizcaychipi MP, Zhang D, Gentleman SM, Maze M, Ma D. Cognitive decline following major surgery is associated with gliosis, beta-amyloid accumulation, and tau phosphorylation in old mice. Crit Care Med. 2010 Nov;38(11):2190-8. doi: 10.1097/CCM.0b013e3181f17bcb.
Results Reference
background
PubMed Identifier
23296426
Citation
Su X, Feng X, Terrando N, Yan Y, Chawla A, Koch LG, Britton SL, Matthay MA, Maze M. Dysfunction of inflammation-resolving pathways is associated with exaggerated postoperative cognitive decline in a rat model of the metabolic syndrome. Mol Med. 2013 Feb 8;18(1):1481-90. doi: 10.2119/molmed.2012.00351.
Results Reference
background
Learn more about this trial
Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium
We'll reach out to this number within 24 hrs