Traumatic Brain InjuryPhase 1/2TBINCT01058395
Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI)
A Phase 1/2 study testing Minocycline in people with Traumatic Brain Injury, run by Wayne State University at 2 sites in United States.
Trial summary
The purpose of this study is: 1. To assess the safety and feasibility of minocycline administration after TBI in a dose escalation study at two different doses over 7 days. 2. To assess the pharmacokinetic characteristics of two different dosing regimens of minocycline in TBI patients, the effect on biochemical… Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Minocycline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2010to Jan 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male , 18 to 75 years of age, irrespective of race;
- Ability to provide written informed consent or have legal representative provide written informed consent;
- Must be enrolled in the study within 6 of injury and meet the following criteria:
- GCS score of 12 or less within the first 4 hours of injury;
- Evidence of neurological injury on computer tomography (CT) of the head;
- No known allergy to minocycline or other contraindication to receiving this medication.
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- Presence of central venous catheter;
- Participants must not have a known life-threatening disease prior to the brain injury: However, individuals with a stable medical illness in the opinion of the investigator may be allowed to enter the study;
- Participants are not to be on any other interventional studies aimed at enhancing neurorecovery;
- Participants are not to be receiving immunosuppressant agents prior to study enrollment.
Who cannot join
- Participant is a female;
- Participants, guardians or legal representatives who are unwilling to cooperate with the investigation;
- Participants who have received any other investigational drug within 30 days of injury;
- Participants known to have severe ischemic heart disease or congestive heart failure, myocardial infarction, spinal cord injury with ongoing deficits, cancer or any other severe illnesses that in the opinion of the investigator would affect the assessment of therapy;
- Participants with an ongoing neurological disease/condition or previous stroke or TBI;
- Known clinical sequelae of spinal cord injury;
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- Massive cerebral hemisphere or brainstem hematoma, incompatible with survival;
- History of major depression requiring the use of the medication at the time of injury;
- Multiple trauma which in the opinion of the investigator, would jeopardize the assessment of therapy;
- Participants who have any type of penetrating head injury;
- Participants receiving chronic steroid treatment;
- Participants receiving isotretinoin;
- Lack of informed consent signed by either the participant or the subject's legal representative;
- Prior TBI, brain tumor, cerebral vascular event, or other stable brain insult;
- Prior history of Pseudotumor cerebri ;
- Patients with known renal failure, BUN/ Creatinine 20:1; creatinine > 2 mg/dl;
- Patients with known hepatic failure, AST/ALT> 3 x Upper Limit of Normal;
- Thrombocytopenia < 75,000/mm;
- Known allergy or sensitivity to any of the tetracyclines or any of the components of the product formulation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Oakwood Dearborn Hospital
Dearborn, Michigan, 48124
Oakwood Southshore Hospital
Trenton, Michigan, 48183
About this study
Official title: Phase I Study of Minocycline in a Dose Escalation Study as a Safe, Efficacious Therapeutic Intervention for Moderate and Severe TBI in Humans
The purpose of this study is:
- To assess the safety and feasibility of minocycline administration after TBI in a dose escalation study at two different doses over 7 days.
- To assess the pharmacokinetic characteristics of two different dosing regimens of minocycline in TBI patients, the effect on biochemical markers of neuroprotective mechanisms, and effect on neurobehavioral and functional outcome.
- To begin initial assessment of the efficacy of minocycline as a therapeutic agent for severe human TBI.
Read the detailed description
The purpose of this preliminary study is to test the hypothesis that administration of minocycline to humans with moderate and severe TBI is both safe and feasible in the acute post-injury setting, and to characterize its disposition and effects on biomarkers of traumatic CNS injury in a Phase IIa trial. The data collected will serve as the basis for a larger Phase IIb clinical trial in a randomized placebo-controlled parallel group design, to investigate further its potential safety and efficacy as a therapeutic agent for severe human TBI.
Tetracycline derivatives, including doxycycline and minocycline, have been shown to be neuroprotective when given after traumatic brain injury (TBI) and ischemia in rodents. In particular, reduced lesion volume and improved neurological outcome have been demonstrated following minocycline treatment of TBI. The proposed mechanism for these observations is multifactorial, and includes inhibition of microglial activation, caspase-mediated apoptosis, and the excitotoxic N-methyl-D-aspartic acid (NMDA) pathway. Because comparable inflammatory, excitotoxic and apoptotic pathways have also been implicated in human TBI, we hypothesize that administration of minocycline will confer neuroprotection after moderate to severe TBI in that milieu as well, with the potential for significant clinical benefit. Minocycline is highly lipophilic, and thus penetrates the human central nervous system (CNS). In addition, it has been shown to be safe when used in non-traumatic human neurological disorders.
- Conditions
- Traumatic Brain Injury
- Being tested
- Minocycline
- Keywords
- Traumatic Brain Injury, Minocycline, Outcome
- Medical subject headings
- Brain Injuries, Traumatic, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Minocin
Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
| Study group | Role | What they receive |
|---|---|---|
| 800 mg loading then 200 mg Q12 | Experimental | Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Receives: Drug: Minocycline |
| 800 mg loading then 400 mg Q12 | Experimental | Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disability Rating Scale
The main outcome measure after the safety data was the Disability Rating Scale (DRS). It is a 29 point scale with 29 being a severe vegetative state. It is reliable across time and demonstrates better sensitivity than the Glasgow Outcome Scale.It has been a standard primary outcome measure for most pharmaceutical studies for TBI, and was required by the FDA for the IND approval.
Measured: 4 weeks and 3 months
Secondary outcomes (1)
Drug Levels
Serum samples were collected for assessment of minocycline concentrations at the estimated time of steady-state concentrations. Serum concentrations were assessed on Day 4. Data reported will be pKa levels 2 hours after AM dose.
Measured: 4 days after start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2010 (estimated)
- Study startFeb 2010
- Primary completionSep 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jay M Meythaler, Wayne State University
- Investigators
- Jay M Meythaler, MD, Principal investigator, Wayne State UniversityKristina Freese, PA, Study director, Wayne State University Dept. PM&R OakwoodJohn Fath, MD, Principal investigator, Oakwood Hospital Dearborn, Trauma Surgery DirectorAllen Lamb, DO, Study director, Oakwood Southshore Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01058395
- Sponsor's protocol ID
- #H133A080044 -01
- Other IDs
- IND# 104298
- Acronym
- TBI
- Status last verified
- Aug 2018
- First submitted
- 19 Jan 2010
- Last updated
- 17 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, Reineke J, Peduzzi-Nelson J, Roskos PT. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33(5):679-689. doi: 10.1080/02699052.2019.1566968. Epub 2019 Feb 12.
PubMed 30744442
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Minocycline in a Dose Escalation Study as a Safe, Efficacious Therapeutic Intervention for Moderate and Severe TBI in Humans
- ClinicalTrials.gov ID
- NCT01058395
- Acronym / sponsor ID
- TBI / #H133A080044 -01
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic Brain Injury, Minocycline, Outcome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Sep 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 28 Jan 2010 (estimated)
- Results
- Posted 17 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is:
- To assess the safety and feasibility of minocycline administration after TBI in a dose escalation study at two different doses over 7 days.
- To assess the pharmacokinetic characteristics of two different dosing regimens of minocycline in TBI patients, the effect on biochemical markers of neuroprotective mechanisms, and effect on neurobehavioral and functional outcome.
- To begin initial assessment of the efficacy of minocycline as a therapeutic agent for severe human TBI.
Detailed description
The purpose of this preliminary study is to test the hypothesis that administration of minocycline to humans with moderate and severe TBI is both safe and feasible in the acute post-injury setting, and to characterize its disposition and effects on biomarkers of traumatic CNS injury in a Phase IIa trial. The data collected will serve as the basis for a larger Phase IIb clinical trial in a randomized placebo-controlled parallel group design, to investigate further its potential safety and efficacy as a therapeutic agent for severe human TBI.
Tetracycline derivatives, including doxycycline and minocycline, have been shown to be neuroprotective when given after traumatic brain injury (TBI) and ischemia in rodents. In particular, reduced lesion volume and improved neurological outcome have been demonstrated following minocycline treatment of TBI. The proposed mechanism for these observations is multifactorial, and includes inhibition of microglial activation, caspase-mediated apoptosis, and the excitotoxic N-methyl-D-aspartic acid (NMDA) pathway. Because comparable inflammatory, excitotoxic and apoptotic pathways have also been implicated in human TBI, we hypothesize that administration of minocycline will confer neuroprotection after moderate to severe TBI in that milieu as well, with the potential for significant clinical benefit. Minocycline is highly lipophilic, and thus penetrates the human central nervous system (CNS). In addition, it has been shown to be safe when used in non-traumatic human neurological disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 800 mg loading then 200 mg Q12 | Experimental | Drug: MinocyclineMinocycline 800 mg. loading followed by 200 mg. Q 12 hours. |
| 800 mg loading then 400 mg Q12 | Experimental | Drug: MinocyclineMinocycline 800 mg. loading followed by 400 mg. Q 12 hours. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male , 18 to 75 years of age, irrespective of race;
- Ability to provide written informed consent or have legal representative provide written informed consent;
- Must be enrolled in the study within 6 of injury and meet the following criteria:
- Presence of central venous catheter;
- Participants must not have a known life-threatening disease prior to the brain injury: However, individuals with a stable medical illness in the opinion of the investigator may be allowed to enter the study;
Key exclusion criteria (19 listed)
- Participant is a female;
- Participants, guardians or legal representatives who are unwilling to cooperate with the investigation;
- Participants who have received any other investigational drug within 30 days of injury;
- Participants known to have severe ischemic heart disease or congestive heart failure, myocardial infarction, spinal cord injury with ongoing deficits, cancer or any other severe illnesses that in the opinion of the investigator would affect the assessment of therapy;
- Participants with an ongoing neurological disease/condition or previous stroke or TBI;
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 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days. | Drug | 800 mg loading then 200 mg Q12, 800 mg loading then 400 mg Q12 |
Primary outcome
Disability Rating Scale
Time frame: 4 weeks and 3 months
The main outcome measure after the safety data was the Disability Rating Scale (DRS). It is a 29 point scale with 29 being a severe vegetative state. It is reliable across time and demonstrates better sensitivity than the Glasgow Outcome Scale.It has been a standard primary outcome measure for most pharmaceutical studies for TBI, and was required by the FDA for the IND approval.
1 secondary outcome
Drug Levels
Time frame: 4 days after start
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30744442Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, Reineke J, Peduzzi-Nelson J, Roskos PT. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33(5):679-689. doi: 10.1080/02699052.2019.1566968. Epub 2019 Feb 12.
- Individual participant dataSharing planned: No
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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.
Jay M Meythaler, MD principal investigator
Wayne State University
Kristina Freese, PA study director
Wayne State University Dept. PM&R Oakwood
John Fath, MD principal investigator
Oakwood Hospital Dearborn, Trauma Surgery Director
2 sites 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 in people with Traumatic Brain Injury, run by Wayne State University at 2 sites 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 10 inclusion and 19 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 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
Yes. Results are posted in the registry (first posted 17 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disability Rating Scale (time frame: 4 weeks and 3 months). 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 NCT01058395, which also lists 1 linked publication.
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 17 Sep 2018.