Carotid StenosisPhase 2NCT00401921
A Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
A Phase 2 study testing Minocycline in people with Carotid Stenosis, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Carotid Stenosis
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Jun 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with carotid stenosis 60% or more with a clinical indication of CEA.
- Patients that can perform the tests in English.
- 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).
- Ages Eligible for Study: 18 Years - 90 Years
- Genders Eligible for Study: Both
Who cannot join
- Known hypersensitivity to tetracyclines
- Advanced cardiac, pulmonary or renal disease as assessed by the PCP of the patient.
- Previous strokes with important clinical neurological deficits.
- Pregnancy, breast-feeding or lactating
- Baseline MMSE score less or equal to 20.
- Female subjects on oral contraceptives.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Randomized, Placebo-Controlled Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
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.
- The null hypothesis is that there is no difference in cognitive performance changes after CEA between the patients that receive placebo or minocycline.
Read the 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:
- Trail making test - parts A and B (this test evaluates visual concept and visuo-motor track)
- Controlled Oral Word Association (letters C, F and L) (this test evaluates verbal fluency)
- The Boston Naming Test (naming of 60 pictures) (this test evaluates left hemisphere damage)
- Digit Span Forward and Backward (this test evaluates working memory)
- Stroop Task (this test evaluates selective attention and mental flexibility)
- 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.
- Conditions
- Carotid Stenosis
- Being tested
- Minocycline, Placebo oral capsule
- Medical subject headings
- Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Minocycline 100mg/Placebo 0mg
100 mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery
Placebo oral capsuleDrug
1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery.
| Study group | Role | What they receive |
|---|---|---|
| Minocycline arm | Placebo comparator | Minocycline 100mg/Placebo 0mg Minocycline 100mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery Receives: Drug: Minocycline |
| Placebo arm | Placebo comparator | Placebo 0mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychological assessment
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2006 (estimated)
- Study startOct 2006
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: PI moved to a new facility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid StenosisStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joanne O'Hara, Brigham and Women's Hospital
- Investigators
- Robert Friedlander, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00401921
- Sponsor's protocol ID
- 2006-P-001225
- Status last verified
- Jul 2017
- First submitted
- 17 Nov 2006
- Last updated
- 14 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy
- ClinicalTrials.gov ID
- NCT00401921
- Acronym / sponsor ID
- 2006-P-001225
- Conditions
- Carotid Stenosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI moved to a new facility
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Oct 2006
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 22 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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 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:
- Trail making test - parts A and B (this test evaluates visual concept and visuo-motor track)
- Controlled Oral Word Association (letters C, F and L) (this test evaluates verbal fluency)
- The Boston Naming Test (naming of 60 pictures) (this test evaluates left hemisphere damage)
- Digit Span Forward and Backward (this test evaluates working memory)
- Stroop Task (this test evaluates selective attention and mental flexibility)
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minocycline arm | Placebo comparator | Drug: MinocyclineMinocycline 100mg/Placebo 0mg Minocycline 100mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery |
| Placebo arm | Placebo comparator | Drug: Placebo oral capsulePlacebo 0mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with carotid stenosis 60% or more with a clinical indication of CEA.
- Patients that can perform the tests in English.
- 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).
- Ages Eligible for Study: 18 Years - 90 Years
- Genders Eligible for Study: Both
Key exclusion criteria (6 listed)
- Known hypersensitivity to tetracyclines
- Advanced cardiac, pulmonary or renal disease as assessed by the PCP of the patient.
- Previous strokes with important clinical neurological deficits.
- Pregnancy, breast-feeding or lactating
- Baseline MMSE score less or equal to 20.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: Minocycline 100mg/Placebo 0mg100 mg, 1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery | Drug | Minocycline arm |
| Placebo oral capsule1 capsule PO BID starting 36 hours prior to surgery. 2 capsules the morning of surgery. | Drug | Placebo arm |
Primary outcome
Neuropsychological assessment
Time frame: 1 day
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Friedlander, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Minocycline in people with Carotid Stenosis, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuropsychological assessment (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2017.