Trial record 2 of 2 for:    Dexmedetomidine and Cognitive Reserve

Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeff Silverstein. MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00561678
First received: November 19, 2007
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD.

Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.


Condition Intervention Phase
Postoperative Delirium
PD
Postoperative Cognitive Dysfunction
POCD
Drug: Precedex (Dexmedetomidine)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Delirium Battery [ Time Frame: post surgery ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: postoperative day 1 ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: postoperative day 2 ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: postoperative day 3 if possible ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: postoperative day 4 if possible ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: postoperative day 5 if possible ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: at 3 months postoperatively ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU

  • Delirium Battery [ Time Frame: at 6 months postoperatively ] [ Designated as safety issue: Yes ]
    Occurrence of Post-Operative Delirium in PACU


Secondary Outcome Measures:
  • Neuropsychological testing [ Time Frame: at 3 months postoperatively ] [ Designated as safety issue: No ]
    Rate of change of cognitive function

  • Neuropsychological testing [ Time Frame: at 6 months postoperatively ] [ Designated as safety issue: No ]
    Rate of change of cognitive function


Enrollment: 403
Study Start Date: February 2008
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Precedex
Precedex (Dexmedetomidine)
Drug: Precedex (Dexmedetomidine)
0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
Other Name: Dexmedetomidine
Placebo Comparator: Placebo
Placebo - normal saline
Drug: Placebo
0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
Other Name: Normal Saline

Detailed Description:

Postoperative Delirium or PD and Postoperative Cognitive Dysfunction or POCD are syndromes of central nervous system dysfunction that significantly complicate the recovery of a proportion of elderly patients following surgery.

Delirium is typically a transient syndrome characterized by a de-novo appearance of several pathognomonic behaviors, including disorientation, decreased attention span, sensory misperceptions, a waxing-and-waning type of confusion, and disorganized thinking. PD typically occurs on postoperative days 1 to 3 and is associated with prolonged hospital stays, increased risks for morbidity and mortality and significant health care expenditures.

The neuroendocrine stress response to surgery, including the immediate postoperative period, remains an important potential etiologic factor. In particular, our data suggests that stress in the immediate postoperative period is poorly controlled by all anesthetic techniques and the normal diurnal variation in cortisol is suppressed in subjects who develop POCD.

Dexmedetomidine is a highly selective alpha 2A agonist currently approved for sedation in the ICU. Dexmedetomidine produces analgesia, sympatholysis, and a light sedation characterized by easy arousal. Its action converges on the endogenous substrates for natural sleep to produce their sedative action, an effect that could prove beneficial to elderly postoperative patients.

We hypothesize that treatment with dexmedetomidine will diminish both PD and POCD. The essential proposition is that modulation of perioperative stress can ameliorate perioperative delirium and cognitive dysfunction.

Based on both the concept of cognitive reserve as well as clinical experience, there is concern that patients with preoperative cognitive impairment are particularly vulnerable to POCD. In general, such patients have been excluded from previous studies. This study is unique in that we will assess all participants for mild cognitive impairment prior to surgery. Assessment of the impact of preexisting cognitive impairment is a secondary aim. A broad goal of this interdisciplinary project is to evaluate POCD, which is primarily an anesthesia concept, in the more general context of dementing illness as explored by geriatric psychiatry.

  Eligibility

Ages Eligible for Study:   68 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 68 and older
  • elective major surgery under general anesthesia(major surgery is defined by a planned 2 day hospitalization)
  • ASA physical status I-III
  • capable and willing to consent
  • MMSE > 20 (to exclude dementia)

Exclusion Criteria:

  • Cardiac surgery
  • Intracranial Surgery
  • Emergency Surgery
  • Patients with severe visual or auditory disorder/handicaps
  • Illiteracy
  • Patients with clinically significant Parkinson's Disease
  • Patients not expected to be able to complete the 3 and 6 month postoperative tests
  • Sick sinus syndrome without pacemaker
  • Hypersensitivity to drug or class
  • Current 2nd or 3rd degree AV block
  • History of clinically significant bradycardia
  • Contraindication to the use of an 2A-agonist
  • Presence of a major psychiatric condition such as bipolar disorder, major depression, schizophrenia, or dementia
  • ASA physical status IV or V
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561678

Locations
United States, Florida
University of Miami Medical Center
Miami, Florida, United States, 33136
United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
United States, Minnesota
The Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
Englewood Hospital & Medical Center
Englewood, New Jersey, United States, 07631
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Jeff Silverstein, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Jeff Silverstein. MD, MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00561678     History of Changes
Other Study ID Numbers: GCO 06-0217, 1R01AG029656-01A1
Study First Received: November 19, 2007
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Postoperative Confusion
Postoperative Delirium
PD
Postoperative Cognitive Dysfunction
POCD

Additional relevant MeSH terms:
Delirium, Dementia, Amnestic, Cognitive Disorders
Dexmedetomidine
Delirium
Cognition Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014