The Effects of Anesthesia on Patients Undergoing Surgery for Repair of a Thoracoabdominal Aneurysm.

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01772537
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 14
• Location: 1
• Arms: 3
• Duration (Months): 21.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Alzheimer's disease represents a growing public health problem in developed countries. Although the pathogenesis is not clearly defined, accumulation of extracellular amyloid, neurofibrillary tangles and neuronal loss are the hallmarks of Alzheimer's disease. The effect of anesthetic agents on changes in these proteins in humans is not well characterized, but in-vitro evidence suggests that anesthetic agents can accelerate potential pathogenic mechanisms, such as increasing amyloid formation or rates of apoptosis in cultured cells and increasing amyloid levels in mice. Human data on the effect of anesthetic agents on amyloid and tau proteins is limited to a small series of 11 patients and showed a significant increase in tau levels after exposure to anesthetics. In this study the investigators propose to measure CSF and serum biomarkers in a population of patients with normal CSF dynamics, who are undergoing surgery for repair of a thoracoabdominal aneurysm. The investigators will also obtain preliminary data on whether changes in CSF levels of these proteins are associated with postoperative delirium or cognitive change.

Condition or Disease	Intervention/Treatment	Phase
Thoracic Aneurysm; Aneurysm Stent; Cardiopulmonary Bypass; Abdominal Aneurysm	Drug: Propofol; Drug: isoflurane	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: The Effect of Anesthesia on Potential Cerebrospinal Fluid (CSF) and Serum Markers of Alzheimer's Disease.
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Open repair of thoracoabdominal aneurysms These will be patients undergoing an open repair of thoracoabdominal aneurysms with or without cardiopulmonary bypass. The will be observational only.
Active Comparator: Stent graft repair of thoracoabdominal aneurysms isoflurane These patients are patients receiving repair of thoracoabdominal aneurysms using stent grafts. These patients will be randomized to receive isoflurane as their primary anesthetic.	Drug: isoflurane
Active Comparator: Stent graft repair of thoracoabdominal aneurysms propofol These patients are patients receiving repair of thoracoabdominal aneurysms using stent grafts. These patients will be randomized to receive propofol as their primary anesthetic.	Drug: Propofol; Intravenous anesthetic

Outcome Measures

Primary Outcome Measures

1. Changes in Cerebrospinal Fluid (CSF) Levels of Tau [From insertion of spinal drain until removal]

   Quantitative levels of tau will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane. .

2. Changes in CSF Levels of Amyloid [From insertion of spinal drain until removal]

   Quantitative levels of amyloid will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane.

Secondary Outcome Measures

1. Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM) [Immediately after surgery and at 3 and 12 months post-op]

   Delirium was measured using the Confusion Assessment Method and the Confusion Assessment Method- Intensive Care Unit (CAM-ICU) based upon post-operative location of patient. The patients were divided into to two groups, patients that had an open thoracoabdominal aneurysm repair versus patients that had stenting of their aneurysms. Patients that had stenting of their aneurysms were also randomized to receive either Propofol or Isoflurane as for their anesthetic.

Other Outcome Measures

1. Serum Inflammatory Markers [From the start of the surgery to 24 hours post-op]

   Serum inflammatory markers will be compared per anesthetic group, Propofol versus Isoflurane. A sample of 10 individuals from each group will have biomarkers measured

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age 21-100 years of age

• Patients presenting for surgical repair of a thoracoabdominal aneurysm

• Insertion of a CSF spinal drain for clinically indicated reason

Exclusion Criteria:

• Patients with pre-existing delirium

• Inability to speak and understand English

• Severe hearing impairment, resulting in inability to converse

• Pregnancy. Pregnancy status will be assessed using a serum pregnancy test during preoperative evaluation as part of the standard of care.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Charles Brown, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01772537
• Other Study ID Numbers: NA_00067716; 5KL2RR025006
• First Posted: Jan 21, 2013
• Last Update Posted: Mar 31, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Johns Hopkins University: thoracoabdominal; aneurysm; open; stent; cardiopulmonary; abdominal; bypass
• Additional relevant MeSH terms: Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Propofol; Isoflurane

Study Results

Participant Flow

Arm/Group Title	Stent Graft Repair Propofol	Stent Graft Repair Isoflurane	Open Repair
Arm/Group Description	Patients have a stent graft repair receiving intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic	standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane	These patient will receive no intervention, just standard of care.
Period Title: Overall Study
STARTED	5	3	6
COMPLETED	4	3	6
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Stent Graft Repair Propofol	Stent Graft Repair Isoflurane	Open Repair	Total
Arm/Group Description	Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic	standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane	These patients received no intervention, just standard of care.	Total of all reporting groups
Overall Participants	5	3	6	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	2 66.7%	3 50%	8 57.1%
>=65 years	2 40%	1 33.3%	3 50%	6 42.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67 (13)	62 (13)	71 (5.3)	65.7 (11.2)
Sex: Female, Male (Count of Participants)
Female	2 40%	1 33.3%	2 33.3%	5 35.7%
Male	3 60%	2 66.7%	4 66.7%	9 64.3%
Region of Enrollment (participants) [Number]
United States	5 100%	3 100%	6 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Cerebrospinal Fluid (CSF) Levels of Tau
Description	Quantitative levels of tau will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane. .
Time Frame	From insertion of spinal drain until removal

Outcome Measure Data

Analysis Population Description

The data for changes in CSF levels of tau are not available. The study did not have adequate funding to appropriately measure these variables.

Arm/Group Title	Propofol	Isoflurane
Arm/Group Description	Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic	standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane
Measure Participants	0	0

2. Primary Outcome

Title	Changes in CSF Levels of Amyloid
Description	Quantitative levels of amyloid will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane.
Time Frame	From insertion of spinal drain until removal

Outcome Measure Data

Analysis Population Description

The data for changes in CSF levels of amyloid are not available. The study did not have adequate funding to appropriately measure these variables.

Arm/Group Title	Propofol	Isoflurane
Arm/Group Description	Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic	standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM)
Description	Delirium was measured using the Confusion Assessment Method and the Confusion Assessment Method- Intensive Care Unit (CAM-ICU) based upon post-operative location of patient. The patients were divided into to two groups, patients that had an open thoracoabdominal aneurysm repair versus patients that had stenting of their aneurysms. Patients that had stenting of their aneurysms were also randomized to receive either Propofol or Isoflurane as for their anesthetic.
Time Frame	Immediately after surgery and at 3 and 12 months post-op

Outcome Measure Data

Analysis Population Description

Of the 6 patients that received an open thoracoabdominal aneurysm repair 2 were found to have delirium. Of the 5 subjects that had stenting and received Propofol as their primary anesthetic, 0 were found to have delirium. Of the 3 stenting subjects that received Isoflurane as their primary anesthetic, 1 were found to have delirium.

Arm/Group Title	Delirum Status Post Open Thoracoabdominal Aneurysm Repair	Delerium Staus Post Stenting of Aneuryms Propofol	Stent Graft Aneurysm Repair Isoflurane
Arm/Group Description	These are participants that received open thoracoabdominal aneurysm repair instead of aneurysm stenting.	These are participants that received stenting of thoracoabdominal aneurysms instead of an open repair and received Propofol as their primary anesthetic.	These are participants that received stenting of thoracoabdominal aneurysms instead of an open repair and received Isoflurane as their primary anesthetic.
Measure Participants	6	5	3
Number [participants]	2 40%	0 0%	1 16.7%

4. Other Pre-specified Outcome

Title	Serum Inflammatory Markers
Description	Serum inflammatory markers will be compared per anesthetic group, Propofol versus Isoflurane. A sample of 10 individuals from each group will have biomarkers measured
Time Frame	From the start of the surgery to 24 hours post-op

Outcome Measure Data

Analysis Population Description

No data is available for serum inflammatory markers. The study did not have adequate funding to appropriately measure these variables.

Arm/Group Title	Propofol	Isoflurane
Arm/Group Description	Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic	standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane
Measure Participants	0	0

Adverse Events

Arm/Group Title	Stent Graft Repair Propofol		Stent Graft Repair Isoflurane		Open Thoracoabdominal Aneurysm Repair
Arm/Group Description	Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol. Propofol: Intravenous anesthetic		standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane. isoflurane		These are patients that received open thoracabdominal aneurysm repair instead of aneurysm stenting.
All Cause Mortality
	Stent Graft Repair Propofol		Stent Graft Repair Isoflurane		Open Thoracoabdominal Aneurysm Repair
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Stent Graft Repair Propofol		Stent Graft Repair Isoflurane		Open Thoracoabdominal Aneurysm Repair
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/3 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Stent Graft Repair Propofol		Stent Graft Repair Isoflurane		Open Thoracoabdominal Aneurysm Repair
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/3 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.