Reproducibility of the 11C-PBR28 PET Signal

NCT02086240 | Withdrawn

• 1 other identifier: 13HH1842
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The Translocator Protein (TSPO) is a protein which reaches very high levels when there is inflammation in the brain. Recently, radioligands have been developed which attach to the TSPO (a radioligand is a drug which has been tagged with radioactivity). Using positron emission tomography (PET) imaging, the radioligand can be detected following injection into a patient. However, it is difficult to accurately measure the amount of TSPO using PET at the moment. This is because the brain does not have a "reference region" for TSPO (ie an area in the brain with no TSPO at all). "Reference regions" are very useful to help work out how much of a PET signal represents "specific binding" (of the radioligand to the target of interest), and how much represents "non specific binding" (of the radioligand to many other structures which are not of interest). In the absence of a reference region, non specific binding can be estimated by giving a drug which binds to the TSPO. The drug prevents the radioligand binding the TSPO and (in a manner of speaking) "creates" a temporary reference region so non specific binding can be measured. To do this, we will use XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor) to bind TSPO and block binding of the PET ligand (\[11C\]PBR28), a TSPO ligand from the phenoxyarlyacetamide class. Most TSPO PET studies (and in one of our previous studies approved by West London REC) quantify the signal using a ratio of specific binding in the brain to radioactivity in the blood. This requires arterial line insertion which is burdensome for subjects, and increases variability. In this study we aim to determine the ratio of specific binding in the brain to nonspecific binding in the brain by using the temporary reference region. For more accuracy the participants will repeat the scanning procedure so determine test-retest variability of the amount of TSPO.

Conditions

Neurodegenerative Disorders

Outcome Measures

Primary Outcomes (1)

• TSPO Binding Status

  Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.

  Baseline/Screening visit

Other Outcomes (1)

• To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.

  1st and 2nd Study Visit (approximately 10 days after the 1st study visit)

Study Arms (1)

XBD173

EXPERIMENTAL

XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor), a drug which binds the TSPO with high affinity. In a previous study (approved by NRES Committee London-West London, REC ref No. 12/LO/0735), we administered an oral dose of XBD173 (up to 90mg) in 12 subjects. No adverse events due to XBD173 occurred and it was well tolerated.

Drug: XBD173

Interventions

XBD173 DRUG

XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor), a drug which binds the TSPO with high affinity.

Also known as: Emapunil

XBD173

Eligibility Criteria

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

You may qualify if:

• Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, and laboratory tests.
• A female subject is eligible to participate if she is a) of non-childbearing potential, defined as premenopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below.
• Male subject must agree to use one of the contraception methods listed below.
• Able to lie comfortably on back for up to 90 minutes at a time.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
• Any clinical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire.
• Contraindications to blood sampling and arterial cannulation.
• Positive Allen's test.
• Prolonged Prothrombin Time.
• Participation in a research study involving ionisation radiation within the last 3 years.
• Significant radiation exposure other than dental Xrays in last 1 year.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NIHR/Wellcome Trust Imperial Clinical Research Facility

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Neurodegenerative Diseases

Interventions

N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide

Condition Hierarchy (Ancestors)

Nervous System Diseases

Study Officials

• David Owen, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: March 13, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2018
• Study Completion: May 1, 2018
• Last Updated: June 10, 2019

Record last verified: 2019-06

Locations

GB (1)