Ignite Creation Date:
2024-05-05 @ 5:11 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00401921
Status:
WITHDRAWN
Last Update Posted:
2017-07-14
First Post:
2006-11-17
Brief Title:
A Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
A Randomized Placebo-Controlled Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
Status:
WITHDRAWN
Status Verified Date:
2017-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
PI moved to a new facility
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary aim of this protocol is to investigate a possible new neuroprotective treatment to prevent cognitive deficits that occur after carotid endarterectomy We will investigate whether a widely used antibiotic agent - minocycline - that has shown neuroprotective effects in animal models of neurological diseases - can reduce the cognitive deficits associated with the surgical procedure of carotid endarterectomy CEA Because these cognitive deficits are believed to be a result of small strokes due to emboli andor hypoperfusion this study will provide preliminary data on the use of this drug as a neuroprotective agent in stroke - a leading cause of disability
1 The first aim of this study is to examine whether 5 doses of minocycline administered 36 hrs before and 1 dose 12 hrs after the surgical procedure in patients undergoing CEA are effective to reduce the cognitive deficits associated with this procedure as compared with placebo
a The null hypothesis is that there is no difference in cognitive performance changes after CEA between the patients that receive placebo or minocycline
1 The first aim of this study is to examine whether 5 doses of minocycline administered 36 hrs before and 1 dose 12 hrs after the surgical procedure in patients undergoing CEA are effective to reduce the cognitive deficits associated with this procedure as compared with placebo
a The null hypothesis is that there is no difference in cognitive performance changes after CEA between the patients that receive placebo or minocycline
Detailed Description:
This protocol is a phase IIa study that will prospectively investigate whether minocycline an antibiotic that showed neuroprotective effects in animal models can decrease the cognitive deficits associated with carotid endarterectomy This trial will be a randomized parallel-group design double-blind placebo controlled clinical trial conducted at the Brigham and Womens Hospital
The principal aim of this investigation is to study the effects of minocycline on cognitive performance after carotid endarterectomy To measure cognitive function we will perform a neuropsychological battery of tests as detailed below This battery of tests will be carried out by a blinded rater a neurologist and will be performed according to the following timetable
Training session before the baseline patients will perform the tasks several times until they reach a stable plateau defined as a variation of less than 10 in the last three trials in order to eliminate the confounding effect of learning
Baseline evaluation the baseline evaluation will be performed in the day prior to the surgery
Post-treatment evaluation post-treatment evaluation will be performed 24 hours after the surgical procedure by the same blinded rater
Neuropsychological battery of tests we based our neuropsychological battery of tests on a similar study that evaluated the cognitive deficits associated with CEA and will consist of the following tests
1 Trail making test - parts A and B this test evaluates visual concept and visuo-motor track
2 Controlled Oral Word Association letters C F and L this test evaluates verbal fluency
3 The Boston Naming Test naming of 60 pictures this test evaluates left hemisphere damage
4 Digit Span Forward and Backward this test evaluates working memory
5 Stroop Task this test evaluates selective attention and mental flexibility
6 Mini-mental state examination this test evaluates an adult patients level of global cognitive functioning
Blood sample analysis As a secondary outcome we will analyze subjects blood sample in respect to two particular substances S100B and neuron specific enolase The rationale for performing proteomic studies is that past research has shown that subtle cerebral injuries after carotid endarterectomy even in the absence of stroke might be associated with a significant increase in serum S100B Connolly 2001 - Neurosurgery 2001 49 5 and also in traumatic brain injury Cotena 2006 J Neurosurg 2006 104 6 In addition neuron specific enolase NSE also seems to be valuable to predict brain damage in patients with brain traumatic injury Naeimi 2006 - Brain Inj 2006 205 thus showing that these two substances might be important biomarkers to be investigated in our study
After eligibility screening inclusion and exclusion criteria consent form medical history and physical exam participants will be randomized to the exposure - minocycline or placebo The pills minocycline and placebo will have the same appearance and only one person will know whether the treatment is active or placebo
Randomization
Because our sample size will be relatively small participants will be randomized to minocycline or placebo through a randomization stratification approach This approach will ensure that both groups will have a similar distribution regarding baseline performance in the cognitive tests Participants will be gathered into groups strata defined by their performance in the neuropsychological tasks baseline Participants within each stratum will be randomized to one of two treatment groups - minocycline and placebo - according to a block randomization of four and using a randomization list generated by a computer that will take into account the study entrance order These groups are defined as follows
Minocycline we will use the dosage of minocycline that is currently used for clinical indications and also used in trials employing this drug as an anti-inflammatory agent Minocycline will be administered in the period of 36 hrs before surgery 100 mg twice a day and 200 mg in the morning of the surgery - total of 5 doses and 12 hrs after surgery single dose of 100 mg
The two doses of minocycline administered in the morning of the surgery will be taken with a small sip of water
Placebo placebo pill will have the same appearance as the real drug minocycline and will be administered using the same timetable as the active drug
The principal aim of this investigation is to study the effects of minocycline on cognitive performance after carotid endarterectomy To measure cognitive function we will perform a neuropsychological battery of tests as detailed below This battery of tests will be carried out by a blinded rater a neurologist and will be performed according to the following timetable
Training session before the baseline patients will perform the tasks several times until they reach a stable plateau defined as a variation of less than 10 in the last three trials in order to eliminate the confounding effect of learning
Baseline evaluation the baseline evaluation will be performed in the day prior to the surgery
Post-treatment evaluation post-treatment evaluation will be performed 24 hours after the surgical procedure by the same blinded rater
Neuropsychological battery of tests we based our neuropsychological battery of tests on a similar study that evaluated the cognitive deficits associated with CEA and will consist of the following tests
1 Trail making test - parts A and B this test evaluates visual concept and visuo-motor track
2 Controlled Oral Word Association letters C F and L this test evaluates verbal fluency
3 The Boston Naming Test naming of 60 pictures this test evaluates left hemisphere damage
4 Digit Span Forward and Backward this test evaluates working memory
5 Stroop Task this test evaluates selective attention and mental flexibility
6 Mini-mental state examination this test evaluates an adult patients level of global cognitive functioning
Blood sample analysis As a secondary outcome we will analyze subjects blood sample in respect to two particular substances S100B and neuron specific enolase The rationale for performing proteomic studies is that past research has shown that subtle cerebral injuries after carotid endarterectomy even in the absence of stroke might be associated with a significant increase in serum S100B Connolly 2001 - Neurosurgery 2001 49 5 and also in traumatic brain injury Cotena 2006 J Neurosurg 2006 104 6 In addition neuron specific enolase NSE also seems to be valuable to predict brain damage in patients with brain traumatic injury Naeimi 2006 - Brain Inj 2006 205 thus showing that these two substances might be important biomarkers to be investigated in our study
After eligibility screening inclusion and exclusion criteria consent form medical history and physical exam participants will be randomized to the exposure - minocycline or placebo The pills minocycline and placebo will have the same appearance and only one person will know whether the treatment is active or placebo
Randomization
Because our sample size will be relatively small participants will be randomized to minocycline or placebo through a randomization stratification approach This approach will ensure that both groups will have a similar distribution regarding baseline performance in the cognitive tests Participants will be gathered into groups strata defined by their performance in the neuropsychological tasks baseline Participants within each stratum will be randomized to one of two treatment groups - minocycline and placebo - according to a block randomization of four and using a randomization list generated by a computer that will take into account the study entrance order These groups are defined as follows
Minocycline we will use the dosage of minocycline that is currently used for clinical indications and also used in trials employing this drug as an anti-inflammatory agent Minocycline will be administered in the period of 36 hrs before surgery 100 mg twice a day and 200 mg in the morning of the surgery - total of 5 doses and 12 hrs after surgery single dose of 100 mg
The two doses of minocycline administered in the morning of the surgery will be taken with a small sip of water
Placebo placebo pill will have the same appearance as the real drug minocycline and will be administered using the same timetable as the active drug
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None