Translocator Protein and Inflammation After Traumatic Brain Injury

NCT01547780 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 12006312-M-0063
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- People with traumatic brain injury (TBI) often have inflammation in the brain. A protein called the translocator protein (TSPO) is often present with inflammation. Researchers want to see if a radioactive chemical known as \[11C\]PBR28 can be used to study TSPO and inflammation in the brain of people with TBI. Objectives: \- To test whether \[11C\]PBR28 can be used to study changes in the brain after a traumatic brain injury. Eligibility:

• Individuals at least 18 years of age who have had TBI and have had a brain scan that shows signs of inflammation.
• Healthy volunteers at least 18 years of age. Design:
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
• All participants will have two brain scans during an outpatient visit. A magnetic resonance imaging scan will study brain activity. A positron emission tomography (PET) scan will use \[11C\]PBR28 to look for signs of TSPO and brain inflammation.
• Participants with TBI will have two PET scans within 10 days of the head injury, and a PET scan around 90 days after the injury. They may also have MRI scans under this or another study. Tests of thinking, memory, and concentration will be used to study the effects of the injury and inflammation

Conditions

Traumatic Brain Injury (TBI); Healthy

Keywords

Positron Emission Tomography (PET); Inflammation; Microglial Activation; Traumatic Brain Injury; TBI

Outcome Measures

Primary Outcomes (2)

• Receptor Binding (Vt)

  To determine total distribution volume of \[C-11\]PBR28 in the whole brain using PET and arterial input function (concentration of radioligand in arterial plasma over time).

  120 minutes from the start of the PET scan

• Receptor Binding Corrected for Plasma (Vt/fp)

  Total distribution volume divided by plasma free fraction (fp) of \[C-11\]PBR28. Measured with PET and arterial input function (concentration of radioligand in arterial plasma over time).

  120 minutes from the start of the PET scan

Study Arms (4)

Baseline brain PET in acute TBI patient

EXPERIMENTAL

Single intravenous injection of \[C-11\]PBR28, \~10-20 mCi, prior to baseline brain positron emission tomography (PET) scan in Acute (\< 5 months post-injury) traumatic brain injury (TBI) patients.

Drug: [11C]PBR28 and Positron Emission Tomography (PET)

Repeat brain PET in acute TBI patient

EXPERIMENTAL

Single intravenous injection of \[C-11\]PBR28, \~10-20 mCi, prior to repeat brain positron emission tomography (PET) scan in Acute (\< 5 months post-injury) traumatic brain injury (TBI) patients.

Drug: [11C]PBR28 and Positron Emission Tomography (PET)

Single brain PET in Chronic TBI patient

EXPERIMENTAL

Single intravenous injection of \[C-11\]PBR28, \~10-20 mCi, prior to brain positron emission tomography (PET) scan in Chronic (5 months - 5 years post-injury) traumatic brain injury (TBI) patients.

Drug: [11C]PBR28 and Positron Emission Tomography (PET)

Single brain PET in healthy subjects

EXPERIMENTAL

Single intravenous injection of \[C-11\]PBR28, \~10-20 mCi, prior to brain positron emission tomography (PET) scan in Healthy Subjects.

Drug: [11C]PBR28 and Positron Emission Tomography (PET)

Interventions

[11C]PBR28 and Positron Emission Tomography (PET) DRUG

Brain PET with \[11C\]PBR28. 11C\]PBR28 is a new PET ligand that images TSPO with high levels of specific binding.

Baseline brain PET in acute TBI patient; Repeat brain PET in acute TBI patient; Single brain PET in Chronic TBI patient; Single brain PET in healthy subjects

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with TBI:
• Group 1 Acute/subacute phase (n = 20)
• Diagnosis of non-penetrating TBI caused by a head injury within approximately 5 months.
• Ambulatory.
• Able to provide self consent without a legally-authorized representative based on the assessment of the Decision-Making Capacity (DMC) by the Human Subjects Protection Unit (HSPU).
• Show abnormal MRI findings consistent with TBI in protocol 10-N-N122 or in the image database of the CNRM Image Processing Core if the subject is recruited from CNRM Recruitment Core protocol 11-N-0084 or another CNRM protocol that allows referrals to other studies.
• Age 18 or older.
• Group 2 Chronic phase (n = 20)
• A head injury approximately 5 months 5 years ago.
• Enrolled in CNRM Recruitment Core protocol 11-N-0084 or another CNRM protocol that allows referral to other studies.
• Meet at least one of the criteria of Probable or Definite TBI established by CNRM.
• Ambulatory.
• Able to provide self consent without a legally-authorized representative based on the assessment of the Decision-Making Capacity (DMC) by the Human Subjects Protection Unit (HSPU).
• Age 18 or older.
• Group 3 Healthy subjects.

You may not qualify if:

• Subjects with TBI for both groups 1 and 2 are not eligible for participation in this research study if any of the following conditions exist:
• Present or past history of brain disease other than TBI.
• Subjects with abnormal MRI findings that suggest a diagnosis other than TBI or a second lesion such as brain tumor in addition to the changes consistent with TBI.
• Serious medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries. The Medical Advisory Investigator of this protocol will determine whether the subject needs to be excluded.
• Contraindication to MRI scanning including certain metal implants or devices such as: cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear, otologic, or ear implant, transdermal medication patch (Nitroglycerine) that cannot be removed for the study, body piercing(s), bone/joint pin, screw, nail, plate, wire sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal imbedded in a subject's body (such as from war wounds or accidents or previous work in metal fields or machines that may have left any metallic fragments in or near the subject's eyes).
• Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.).
• In female subjects, pregnancy or breastfeeding.
• Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
• HEALTHY SUBJECTS ARE NOT ELIGIBLE FOR PARTICIPATION IN THIS RESEARCH IF ANY OF THE FOLLOWING CONDITIONS EXIST:
• Any past or present history of DSM Axis I disorder, with the exception of substance abuse that ended over 6 months prior to enrollment.
• Contraindication to MRI scanning including certain metal implants or devices such as: cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear, otologic, or ear implant, transdermal medication patch (Nitroglycerine) that cannot be removed for the study, body piercing(s), bone/joint pin, screw, nail, plate, wire sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal imbedded in a subject's body (such as from war wounds or accidents or previous work in metal fields or machines that may have left any metallic fragments in or near the subject's eyes).
• Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.).
• In female subjects, pregnancy or breastfeeding.
• Clinically significant laboratory abnormalities, as defined as laboratory values that are out of normal range or require clinical workup and/or treatment.
• Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead
• Suburban Hospital: collaborator
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Brown AK, Fujita M, Fujimura Y, Liow JS, Stabin M, Ryu YH, Imaizumi M, Hong J, Pike VW, Innis RB. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med. 2007 Dec;48(12):2072-9. doi: 10.2967/jnumed.107.044842. Epub 2007 Nov 15.

  PMID: 18006619 BACKGROUND

• Cernak I, O'Connor C, Vink R. Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats. Clin Exp Pharmacol Physiol. 2001 Nov;28(11):922-5. doi: 10.1046/j.1440-1681.2001.03549.x.

  PMID: 11703397 BACKGROUND

• Conzen M, Ebel H, Swart E, Skreczek W, Dette M, Oppel F. Long-term neuropsychological outcome after severe head injury with good recovery. Brain Inj. 1992 Jan-Feb;6(1):45-52. doi: 10.3109/02699059209008121.

  PMID: 1739852 BACKGROUND

• Paul S, Gallagher E, Liow JS, Mabins S, Henry K, Zoghbi SS, Gunn RN, Kreisl WC, Richards EM, Zanotti-Fregonara P, Morse CL, Hong J, Kowalski A, Pike VW, Innis RB, Fujita M. Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.

  PMID: 29749279 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Inflammation

Interventions

(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Robert Innis
• Organization: National Institute of Mental Health

innisr@mail.nih.gov

+1 301 594 1368

Study Officials

• Robert Innis, MD, PhD

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: March 8, 2012
• Study Start: January 20, 2012
• Primary Completion: September 28, 2017
• Study Completion: September 28, 2017
• Last Updated: July 30, 2021
• Results First Posted: July 30, 2021

Record last verified: 2017-09-28

Locations

US (1)