Spinal Cord InjuriesPhase 1/2NCT00559494
Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury
A Phase 1/2 study testing Minocycline and SCPP augmentation in people with Spinal Cord Injuries, run by University of Calgary at 1 site in Canada.
Trial summary
While research in animal models of spinal cord injury have provided many promising insights, human studies have failed to produce effective therapies. We propose to investigate the drug Minocycline (a metalloproteinase inhibitor) for the treatment of spinal cord injured patients aiming to limit neurological injury and… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Spinal Cord Injuries
- What is being tested?
- Minocycline and SCPP augmentation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2004to Aug 2010
- Phase
- Phase 1/2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 or over
- Motor complete or motor incomplete acute spinal cord injury involving bony spinal levels between C0 and T11
- Patient able to provide informed consent
- Randomization and commencement of administration of first drug dose within 12 hours of injury
- surgical decompression if needed to be performed within 24 hours of the injury
- subjects exhibiting spinal cord perfusion pressure (lumbar drain transduced pressure - mean arterial pressure)> 75 mmHg will be randomized to active augmentation protocol versus maintenance of mean arterial pressure
Who cannot join
- Acute spinal cord injury >12 hours old
- Isolated sensory deficit, motor intact
- Isolated cauda equina injury or injury at bony level T12 or below
- History of systemic lupus erythematosus (SLE)
- Pre-existing hepatic or renal disease
- Tetracycline hypersensitivity
Show all 14Show fewer
- Pregnancy or breast feeding
- Isolated sensory deficit
- Isolated radicular motor deficit
- Significant leukopenia (white blood cell count < ½ times the lower limit of normal) at screening
- Elevated liver function tests (AST, ALT, alkaline phosphatase, or total bilirubin > 2 times the upper limit of normal) at screening
- Presence of systemic disease that might interfere with patient safety, compliance or evaluation of the condition under study (e.g. insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, HIV, HTLV-1)
- Associated traumatic conditions interfering with informed consent or outcome assessment (e.g. closed head injury, liver contusion)
- Known uncorrected severe coronary artery disease or evidence of active coronary ischemia (ECG changes, positive Troponin) will be excluded from SCPP randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury
While research in animal models of spinal cord injury have provided many promising insights, human studies have failed to produce effective therapies. We propose to investigate the drug Minocycline (a metalloproteinase inhibitor) for the treatment of spinal cord injured patients aiming to limit neurological injury and improve neurological outcome. This drug influences several secondary injury mechanisms implicated in spinal cord injury and has been effective in improving outcome after spinal cord injury in animal models. We also propose to examine the safety and feasibility of spinal cord perfusion pressure augmentation with a protocol of IV fluids and inotrope medications versus standard maintenance of mean arterial pressure in subjects who exhibit a decrease in perfusion pressure to less than 75 mmHg. The purpose of this pilot study is 1) to evaluate the feasibility of a clinical trial protocol for Minocycline in patients with acute spinal cord injury, and 2) to ensure adequate drug dosing and metabolic effect. After undergoing a process of informed consent, patients agreeing to participate in the study will be randomized to placebo or treatment groups in a double-blind fashion. Clinical neurological examinations, patient-reported quality of life, and functional independence categorization will be combined with serum and cerebrospinal fluid laboratory investigations to establish some of the pharmacological properties and the safety profile of this medication in this group of patients. In addition, patient tolerance to the dosing regimen will be assessed. The results of this study will provide the preliminary data necessary to plan for a larger prospective, randomized, controlled, double-blind clinical trial to assess efficacy and to further assess safety.
- Conditions
- Spinal Cord Injuries
- Being tested
- Minocycline, placebo, SCPP augmentation, SCPP control
- Keywords
- complete spinal cord injury, incomplete spinal cord injury, central cord spinal cord injury, traumatic
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Minocin
Minocycline IV BID x 7 days (first 10 patients 200 mg/dose, subsequent patients adjusted based on pharmacodynamic profiling to 800 mg loading dose, tapered 100 mg each dose to 400 mg then maintain at 400mg until day 7)
placeboDrug
Also called control, saline
Normal saline 250cc via central line similar to minocycline arm administration protocol
SCPP augmentationProcedure or surgery
maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol
SCPP controlProcedure or surgery
maintenance of Mean arterial pressure of >65 mmHg with fluids and inotropes protocol without spinal cord perfusion pressure as target or guiding therapy
| Study group | Role | What they receive |
|---|---|---|
| Minocycline | Experimental | Not described Receives: Drug: Minocycline |
| Placebo | Placebo comparator | Not described Receives: Drug: placebo |
| SCPP augmentation | Experimental | Not described Receives: Procedure: SCPP augmentation |
| SCPP control | Sham comparator | Not described Receives: Procedure: SCPP control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protocol compliance, feasibility and adverse events
Measured: 2 years
Secondary outcomes (7)
American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
Measured: 2 years
Short Form 36 - Quality of Life Assessment
Measured: 2 years
Functional Independence Measure
Measured: 2 years
London Handicap Scale
Measured: 2 years
Spinal Cord Injury Measure
Measured: 2 years
CSF collection (6/day) and biochemical assays
Measured: 7 days
Sequential Anatomical MRI
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2007 (estimated)
- Study startJun 2004
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Paralyzed Veterans of America, American Association of Neurological Surgeons, Hotchkiss Brain Institute, University of Calgary
- Responsible party
- Principal investigator, Steve Casha, University of Calgary
- Investigators
- Steven Casha, MD PhD FRCSC, Principal investigator, University of CalgaryR. John Hurlbert, MD PhD FRCSC, Principal investigator, University of CalgaryDavid Zygun, MD MSc, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00559494
- Sponsor's protocol ID
- 17007
- Other IDs
- PVA2414
- Status last verified
- Mar 2013
- First submitted
- 14 Nov 2007
- Last updated
- 18 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.
PubMed 22505632Carnini A, Casha S, Yong VW, Hurlbert RJ, Braun JE. Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury. Prion. 2010 Apr-Jun;4(2):80-6. doi: 10.4161/pri.4.2.11756. Epub 2010 Apr 10.
PubMed 20418657
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT00559494
- Acronym / sponsor ID
- 17007
- Conditions
- Spinal Cord Injuries
- Keywords
- complete spinal cord injury, incomplete spinal cord injury, central cord spinal cord injury, traumatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Paralyzed Veterans of America, American Association of Neurological Surgeons, Hotchkiss Brain Institute, University of Calgary
- Study start
- Jun 2004
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 16 Nov 2007 (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.
While research in animal models of spinal cord injury have provided many promising insights, human studies have failed to produce effective therapies. We propose to investigate the drug Minocycline (a metalloproteinase inhibitor) for the treatment of spinal cord injured patients aiming to limit neurological injury and improve neurological outcome. This drug influences several secondary injury mechanisms implicated in spinal cord injury and has been effective in improving outcome after spinal cord injury in animal models. We also propose to examine the safety and feasibility of spinal cord perfusion pressure augmentation with a protocol of IV fluids and inotrope medications versus standard maintenance of mean arterial pressure in subjects who exhibit a decrease in perfusion pressure to less than 75 mmHg. The purpose of this pilot study is 1) to evaluate the feasibility of a clinical trial protocol for Minocycline in patients with acute spinal cord injury, and 2) to ensure adequate drug dosing and metabolic effect. After undergoing a process of informed consent, patients agreeing to participate in the study will be randomized to placebo or treatment groups in a double-blind fashion. Clinical neurological examinations, patient-reported quality of life, and functional independence categorization will be combined with serum and cerebrospinal fluid laboratory investigations to establish some of the pharmacological properties and the safety profile of this medication in this group of patients. In addition, patient tolerance to the dosing regimen will be assessed. The results of this study will provide the preliminary data necessary to plan for a larger prospective, randomized, controlled, double-blind clinical trial to assess efficacy and to further assess safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Experimental | Drug: Minocycline |
| Placebo | Placebo comparator | Drug: placebo |
| SCPP augmentation | Experimental | Procedure: SCPP augmentation |
| SCPP control | Sham comparator | Procedure: SCPP control |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age 16 or over
- Motor complete or motor incomplete acute spinal cord injury involving bony spinal levels between C0 and T11
- Patient able to provide informed consent
- Randomization and commencement of administration of first drug dose within 12 hours of injury
- surgical decompression if needed to be performed within 24 hours of the injury
Key exclusion criteria (14 listed)
- Acute spinal cord injury >12 hours old
- Isolated sensory deficit, motor intact
- Isolated cauda equina injury or injury at bony level T12 or below
- History of systemic lupus erythematosus (SLE)
- Pre-existing hepatic or renal disease
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: MinocinMinocycline IV BID x 7 days (first 10 patients 200 mg/dose, subsequent patients adjusted based on pharmacodynamic profiling to 800 mg loading dose, tapered 100 mg each dose to 400 mg then maintain at 400mg until day 7) | Drug | Minocycline |
| placeboAlso: control, salineNormal saline 250cc via central line similar to minocycline arm administration protocol | Drug | Placebo |
| SCPP augmentationmaintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol | Procedure or surgery | SCPP augmentation |
| SCPP controlmaintenance of Mean arterial pressure of >65 mmHg with fluids and inotropes protocol without spinal cord perfusion pressure as target or guiding therapy | Procedure or surgery | SCPP control |
Primary outcome
Protocol compliance, feasibility and adverse events
Time frame: 2 years
7 secondary outcomes
American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
Time frame: 2 years
Short Form 36 - Quality of Life Assessment
Time frame: 2 years
Functional Independence Measure
Time frame: 2 years
London Handicap Scale
Time frame: 2 years
Spinal Cord Injury Measure
Time frame: 2 years
CSF collection (6/day) and biochemical assays
Time frame: 7 days
Sequential Anatomical MRI
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2013.
- Results publication: PubMed 22505632Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.
- Derived from this study: PubMed 20418657Carnini A, Casha S, Yong VW, Hurlbert RJ, Braun JE. Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury. Prion. 2010 Apr-Jun;4(2):80-6. doi: 10.4161/pri.4.2.11756. Epub 2010 Apr 10.
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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.
Steven Casha, MD PhD FRCSC principal investigator
University of Calgary
R. John Hurlbert, MD PhD FRCSC principal investigator
University of Calgary
David Zygun, MD MSc principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Minocycline and SCPP augmentation in people with Spinal Cord Injuries, run by University of Calgary at 1 site in Canada.
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 6 inclusion and 14 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: finished, as of the sponsor's last update on 18 Mar 2013. 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 Canada. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Protocol compliance, feasibility and adverse events (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00559494, which also lists 2 linked publications.
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 18 Mar 2013.