Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium

Prostate Cancer Clinical Trial

— MAPOCD  

Official title:

Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium: A Multicenter, Randomized, Double-Blind Clinical Trail

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02928692
• Other study ID #: 20158202
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: December 2021

Study information

• Verified date: January 2020
• Source: RenJi Hospital
• Contact: Diansan Su, Doctor
• Phone: 18616514088
• Email: diansansu[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

For the placebo and minocycline group;

Inclusion Criteria:

1. Elder than 65 years old

2. Speak Chinese Mandarin

3. Those who will undergo major general surgery like colorectal cancer excision, major urinary surgery like radical prostatectomy and radical nephrectomy

4. Signed the inform consent

5. American Society of Anesthesiologists classification I to III

Exclusion Criteria:

1. Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;

2. Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;

3. Severe audition or vision disorder;

4. Unwillingness to comply with the protocol or procedures.

5. Cannot communicated with Chinese Mandarin

6. With severe skin disease

7. Serious heart or liver or renal insufficiency patients

8. Had surgery in the past 30 days

9. Allergy to tetracycline or minocycline

For the health volunteers;

Inclusion Criteria:

1. Elder than 65 years old

2. Speak Chinese Mandarin

3. Signed the inform consent

4. No major disease health people

Exclusion Criteria:

1. Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis;

2. Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24;

3. Severe audition or vision disorder;

4. Unwillingness to comply with the protocol or procedures.

5. Cannot communicated with Chinese Mandarin

6. Drug abuse, alcoholism

7. Serious heart or liver or renal insufficiency patients

8. Had surgery in the past 30 days

9. Plan to undergo surgery in the following 3 months.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma of the Rectum
• Carcinoma, Renal Cell
• Cognitive Dysfunction
• Colon Cancer
• Delirium
• Kidney Neoplasms
• Prostate Cancer
• Renal Carcinoma

Intervention

Drug:
• Minocycline

• Placebo

Locations

Country	Name	City	State
China	Scales	Shanghai	Shanghai
China	Shanghai Pudong Hospital	Shanghai
China	Shanghai Pudong New Area Dongming Community Health Care Center	Shanghai
China	Shanghai Pudong New Area people's Hopsital	Shanghai
China	Shanghai Tenth Hospital	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
RenJi Hospital	Pudong New Area People's Hospital, Shanghai 10th People's Hospital, Shanghai Pudong Hospital, Shanghai Pudong New Aera Dongming Community Health Care Center

Country where clinical trial is conducted

China, 

References & Publications (21)

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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum in: Lancet 1998 Jun 6;351(9117):1742. — View 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. — View 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. Review. — View 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. — View 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. Review. — View Citation

Sauër 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. Review. — View 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. Review. — View 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. — View 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;18:1481-90. doi: 10.2119/molmed.2012.00351. — View 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. — View Citation

Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106:161-78. doi: 10.1093/bmb/ldt006. Epub 2013 Apr 4. Review. — View 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. — View 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. Review. — View 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. — View 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, ß-amyloid accumulation, and t phosphorylation in old mice. Crit Care Med. 2010 Nov;38(11):2190-8. doi: 10.1097/CCM.0b013e3181f17bcb. — View 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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	POCD incidence 7 days (or before leaving hospital) after surgery		7 days (or before leaving hospital)
Primary	POD incidence		1 to 5 days after surgery
Secondary	POCD incidence 2 months after surgery		2 months after surgery