Traumatic Brain InjuryPhase 1/2NCT02496975
Traumatic Brain Injury and Effects of Acute Cyclosporine A
A Phase 1/2 study testing Cyclosporine A in people with Traumatic Brain Injury, run by Edward Hall,PhD at 1 site in United States.
Trial summary
This is a prospective, randomized, placebo-controlled study about Cyclosporine A (CSP) and traumatic brain injury (TBI). Cyclosporine A is a drug already marketed and available for other diseases, but is not approved by the Food and Drug Administration for treatment of traumatic brain injury. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Cyclosporine A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2017to 7 Aug 2017
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is between the ages of 18 and 65
- Participant speaks and understands English
- CT Scan evidence of severe TBI
- Post resuscitation GSC 4-8 with at least one reactive pupil
- motor score of greater than 5
- Study medication will be administered within 8 hours injury
Who cannot join
- Participant received high dose systemic corticosteroids, such as Methylprednisolone >15 mg/kg or equivalent,
- Participant has a known allergy to cyclosporine A,
- Participant is pregnant,
- Participant is less than 18 years of age or greater than 65 years of
- Participant has a history of kidney problems, history of stroke or spinal cord injury,
- Participant has a history of cardiovascular disease, or use of immunosuppressive therapy in the last three months,
Show all 9Show fewer
- Participant has a history of malignant tumors unless they have been in remission at least five years.
- Participant has an active infection
- Participant has taken part in another investigational trial within the last 30 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Medical Center
Lexington, Kentucky, 40536
About this study
Official title: Oxidative Damage and Calcium-Activated Proteolytic Biomarkers After Traumatic Brain Injury and Effects of Acute Cyclosporine A
This is a prospective, randomized, placebo-controlled study about Cyclosporine A (CSP) and traumatic brain injury (TBI). Cyclosporine A is a drug already marketed and available for other diseases, but is not approved by the Food and Drug Administration for treatment of traumatic brain injury. The effect of Cyclosporine A on chemicals produced following brain injury is being determined using doses no larger than those used for patients having organ transplant. It is also being given for a much shorter time period (3 days). It is not know if side effects seen in patients taking cyclosporine A will occur when it is given for only 3 days. It is not known if patients with brain injury that are treated with cyclosporine A will have side effects like those seen in organ transplant patients.
Read the detailed description
The purpose of this research study is to measure the chemicals produced by the brain after it is injured and also if Cyclosporine A treatment changes these chemicals. By doing this study, the investigators hope to learn if cyclosporine A therapy helps patients with this injury.
The research procedures will happen at the University of Kentucky (UK) Chandler Medical Center. The study will last for the first 7 days while the participant is admitted to UK Medical Center, or until they are released. Participants will not be asked to stay longer in the hospital for this research study.
Participants in this study will receive all therapies currently available for treatment of severe brain injury. Each participant will be assigned randomly (by chance) to either placebo (a substance without active drug) or cyclosporine A treatment. Neither the participant nor any of the study personnel will know what study treatment has been assigned to the participant.
If assigned to the cyclosporine A treatment group (study drug) participants will be continuously administered the study drug through a tube placed into the vein. A placebo will be given to participants assigned to the placebo group.
Blood and cerebrospinal fluid will be collected at the following time points (12, 24, 36, 48, 60 and 72 hours) for research purposes. These tests will help us understand the participant's ability to make red and white blood cells to fight infection, how well their kidneys function, how well their liver functions, and triglyceride/cholesterol levels.
Cerebrospinal fluid will only be collected from participants who have a drain catheter placed as part of their routine care.
Daily blood collections will occur so the investigators can measure how much of the study drug is present, to assess the body chemicals from the brain and also for safety. Blood samples will be collected by using an already placed line through a vein or artery, or by puncturing the skin with a needle. The chemicals will be measured daily in the urine and also any fluid draining from the line placed into the head for medical management for up to 7 days.
Any unexpected events (side effects) possibly caused by cyclosporine A will be noted and medically managed by the physician. The investigators will be notified when there is need for intervention.
After up to three days of continuous dosing, the study drug will be stopped, but the participant will continue to be carefully monitored for up to 7 days, or until they are released.
Participants will receive the usual treatment for severe traumatic brain injury in addition to receiving the cyclosporine A treatment or placebo.
- Conditions
- Traumatic Brain Injury
- Being tested
- Cyclosporine A, Placebo
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclosporine ADrug
Participants will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours)
PlaceboOther
Participants will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours)
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporine A | Experimental | Participants assigned to this group will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) Receives: Drug: Cyclosporine A |
| Placebo | Active comparator | Participants assigned to this group will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum lipid peroxidation products: isoprostanes and neuroprostaneses measured by gas-chromatography with mass spectometry
Serum lipid peroxidation products will be measured by gas-chromatography with mass spectometry
Measured: first 7 days after TBI
Cerebrospinal fluid (CSF) calpain-mediated cytoskeletal breakdown products measured by western blotting
cytoskeletal breakdown products will be measured by western blotting
Measured: first 7 days after TBI
Secondary outcomes (1)
ICP Therapy Intensity Level (TIL) Summary
The intensity of the use of therapeutic maneuvers to maintain intracranial pressure levels below 20 mm Hg
Measured: first 7 days after TBI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study start7 Aug 2017
- Primary completion7 Aug 2017
- Study completion7 Aug 2017
Why it stopped: Recent studies suggest that cyclosporine A has a very sharp biphasic dose-response problem that is going to make further clinical translation difficult.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Edward Hall,PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Edward Hall,PhD, University of Kentucky
- Investigators
- Edward Hall, PhD, Principal investigator, Sponsor-Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02496975
- Sponsor's protocol ID
- 14-0469-F6A
- Status last verified
- Oct 2017
- First submitted
- 3 Feb 2015
- Last updated
- 26 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hatton J, Rosbolt B, Empey P, Kryscio R, Young B. Dosing and safety of cyclosporine in patients with severe brain injury. J Neurosurg. 2008 Oct;109(4):699-707. doi: 10.3171/JNS/2008/109/10/0699.
PubMed 18826358
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Damage and Calcium-Activated Proteolytic Biomarkers After Traumatic Brain Injury and Effects of Acute Cyclosporine A
- ClinicalTrials.gov ID
- NCT02496975
- Acronym / sponsor ID
- 14-0469-F6A
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Recent studies suggest that cyclosporine A has a very sharp biphasic dose-response problem that is going to make further clinical translation difficult.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Edward Hall,PhDUniversity, hospital or other
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 7 Aug 2017 (actual)
- Study completion
- 7 Aug 2017 (actual)
- First posted
- 14 Jul 2015 (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.
This is a prospective, randomized, placebo-controlled study about Cyclosporine A (CSP) and traumatic brain injury (TBI). Cyclosporine A is a drug already marketed and available for other diseases, but is not approved by the Food and Drug Administration for treatment of traumatic brain injury. The effect of Cyclosporine A on chemicals produced following brain injury is being determined using doses no larger than those used for patients having organ transplant. It is also being given for a much shorter time period (3 days). It is not know if side effects seen in patients taking cyclosporine A will occur when it is given for only 3 days. It is not known if patients with brain injury that are treated with cyclosporine A will have side effects like those seen in organ transplant patients.
Detailed description
The purpose of this research study is to measure the chemicals produced by the brain after it is injured and also if Cyclosporine A treatment changes these chemicals. By doing this study, the investigators hope to learn if cyclosporine A therapy helps patients with this injury.
The research procedures will happen at the University of Kentucky (UK) Chandler Medical Center. The study will last for the first 7 days while the participant is admitted to UK Medical Center, or until they are released. Participants will not be asked to stay longer in the hospital for this research study.
Participants in this study will receive all therapies currently available for treatment of severe brain injury. Each participant will be assigned randomly (by chance) to either placebo (a substance without active drug) or cyclosporine A treatment. Neither the participant nor any of the study personnel will know what study treatment has been assigned to the participant.
If assigned to the cyclosporine A treatment group (study drug) participants will be continuously administered the study drug through a tube placed into the vein. A placebo will be given to participants assigned to the placebo group.
Blood and cerebrospinal fluid will be collected at the following time points (12, 24, 36, 48, 60 and 72 hours) for research purposes. These tests will help us understand the participant's ability to make red and white blood cells to fight infection, how well their kidneys function, how well their liver functions, and triglyceride/cholesterol levels.
Cerebrospinal fluid will only be collected from participants who have a drain catheter placed as part of their routine care.
Daily blood collections will occur so the investigators can measure how much of the study drug is present, to assess the body chemicals from the brain and also for safety. Blood samples will be collected by using an already placed line through a vein or artery, or by puncturing the skin with a needle. The chemicals will be measured daily in the urine and also any fluid draining from the line placed into the head for medical management for up to 7 days.
Any unexpected events (side effects) possibly caused by cyclosporine A will be noted and medically managed by the physician. The investigators will be notified when there is need for intervention.
After up to three days of continuous dosing, the study drug will be stopped, but the participant will continue to be carefully monitored for up to 7 days, or until they are released.
Participants will receive the usual treatment for severe traumatic brain injury in addition to receiving the cyclosporine A treatment or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporine A | Experimental | Drug: Cyclosporine AParticipants assigned to this group will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) |
| Placebo | Active comparator | Other: PlaceboParticipants assigned to this group will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participant is between the ages of 18 and 65
- Participant speaks and understands English
- CT Scan evidence of severe TBI
- Post resuscitation GSC 4-8 with at least one reactive pupil
- motor score of greater than 5
Key exclusion criteria (9 listed)
- Participant received high dose systemic corticosteroids, such as Methylprednisolone >15 mg/kg or equivalent,
- Participant has a known allergy to cyclosporine A,
- Participant is pregnant,
- Participant is less than 18 years of age or greater than 65 years of
- Participant has a history of kidney problems, history of stroke or spinal cord injury,
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 |
|---|---|---|
| Cyclosporine AParticipants will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) | Drug | Cyclosporine A |
| PlaceboParticipants will receive 2.5mg/kg load then 5mg/kg qd continuous infusion x 3 days (72hours) | Other | Placebo |
Primary outcome
Serum lipid peroxidation products: isoprostanes and neuroprostaneses measured by gas-chromatography with mass spectometry
Time frame: first 7 days after TBI
Serum lipid peroxidation products will be measured by gas-chromatography with mass spectometry
Cerebrospinal fluid (CSF) calpain-mediated cytoskeletal breakdown products measured by western blotting
Time frame: first 7 days after TBI
cytoskeletal breakdown products will be measured by western blotting
1 secondary outcome
ICP Therapy Intensity Level (TIL) Summary
Time frame: first 7 days after TBI
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 26 Oct 2017.
- Background: PubMed 18826358Hatton J, Rosbolt B, Empey P, Kryscio R, Young B. Dosing and safety of cyclosporine in patients with severe brain injury. J Neurosurg. 2008 Oct;109(4):699-707. doi: 10.3171/JNS/2008/109/10/0699.
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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.
Edward Hall, PhD principal investigator
Sponsor-Investigator
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 Cyclosporine A in people with Traumatic Brain Injury, run by Edward Hall,PhD 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 6 inclusion and 9 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 26 Oct 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. 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 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?
Serum lipid peroxidation products: isoprostanes and neuroprostaneses measured by gas-chromatography with mass spectometry (time frame: first 7 days after TBI). The study lists 2 primary outcomes in all. 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 NCT02496975, 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 26 Oct 2017.