A Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
Information source: Brigham and Women's Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Carotid Stenosis
Intervention: Minocycline (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Brigham and Women's Hospital Official(s) and/or principal investigator(s): Robert Friedlander, MD, Principal Investigator, Affiliation: Brigham and Women's Hospital
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 and/or
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.
Clinical Details
Official title: A Randomized, Placebo-Controlled Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Primary outcome: Neuropsychological assessment
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 Women's 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 patient's 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 20(5)), 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 90 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients with carotid stenosis 60% or more with a clinical indication of CEA.
2. Patients that can perform the tests in English.
3. Women of childbearing age must be non-lactating and surgically sterile or using an
effective method of birth control and have a negative pregnancy test (adequate birth
control includes use of intra uterine device, or a barrier method, e. g. condom,
diaphragm).
4. Ages Eligible for Study: 18 Years - 90 Years
5. Genders Eligible for Study: Both
Exclusion Criteria:
1. Known hypersensitivity to tetracyclines
2. Advanced cardiac, pulmonary or renal disease as assessed by the PCP of the patient.
3. Previous strokes with important clinical neurological deficits.
4. Pregnancy, breast-feeding or lactating
5. Baseline MMSE score less or equal to 20.
6. Female subjects on oral contraceptives.
Locations and Contacts
Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
Additional Information
Starting date: October 2006
Last updated: June 22, 2011
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