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CompletedNCT00526916Updated Dec 12, 2019

PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Neurocysticercosis Using [C-11]PBR28

A Phase 1 interventional study of [C-11]PBR28 in Neurocysticercosis and Healthy, sponsored by National Institute of Mental Health (NIMH). Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-12-12.

Sponsored by National Institute of Mental Health (NIMH) · Phase 1, Interventional, and Diagnostic

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this protocol is to measure peripheral benzodiazepine receptors in the brain using positron emission tomography (PET) and compare the imaging results between patients and healthy people.

Read the detailed description

Objective

In endemic regions neurocysticercosis is the most common cause of adult acquired epilepsy and thus an important public health problem. The disease is caused by infection with the larval form of the tapeworm, Taenia solium. Although neurocysticercosis is common only in many developing regions, an increased number of patients are diagnosed in developed countries mostly due to immigration of infected individuals.

The peripheral benzodiazepine receptor (PBR) can be a clinically useful marker to detect neuroinflammation because activated microglia in inflammatory areas expresses much greater levels of PBR than in microglia in resting conditions. PBR has been imaged with positron emission tomography (PET) using [(11)C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195), which provides low levels of specific signal. Recently we developed a new ligand, [(11)C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28), which showed much greater specific signal than [(11)C]PK11195 in non-human primates.

The major objective of this protocol is to assess the utility of [(11)C]PBR28 PET to detect neuroinflammation in patients with neurocysticercosis.

Study population

Thirty patients will be recruited and clinically followed under protocol 85-I-0127, Treatment of Cysticercosis including Neurocysticercosis with Praziquantel or Albendazole, (PI: Theodore E. Nash, MD, NIAID). Thirty healthy subjects will be recruited.

Design

Fifteen patients with neurocysticercosis and the first 15 age-matched healthy subjects will have brain PET scans. Patients will have up to three [(11)C]PBR28 PET scans during the follow-up and the treatment under 85-I-0127, typically a few weeks apart.

Outcome measures

PBR28 binding will be compared with clinical symptoms and MRI findings. In addition, the binding will be compared between patients and age-matched control subjects because the high levels of specific binding may allow detection of an increase of PBR in regions where MRI does not detect inflammation.

02

Conditions studied

  • Neurocysticercosis
  • Healthy

Keywords

  • Epilepsy
  • Taenia Solium
  • Microglia
  • Neuroinflammation
  • Compartment Model
  • Neurocysticercosis
  • Healthy Volunteer
  • HV
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

Common to patients with neurocysticercosis and healthy subjects:

Ages between 18 and 75, inclusive.

Patients must meet the inclusion criteria of protocol 85-I-0127.

CONTROL SUBJECTS:

Are healthy based on history, physical exams, ECG, and lab tests.

Exclusion criteria

EXCLUSION CRITERIA:

COMMON TO ALL SUBJECTS:

Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.

ECG with clinically significant abnormalities. Any existing physical exam and ECG within one year will be reviewed and if none already exists in the chart, these will be obtained and reviewed.

Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual guideline of RSC.

Pregnancy or breast feeding.

Claustrophobia.

Positive HIV test.

Cannot lie on back for a few hours for the PET scans.

Presence of ferromagnetic metal in the body or heart pacemaker.

ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS:

Medically unstable.

Seizures are not well controlled with medications.

A history of brain disease other than neurocysticercosis.

Laboratory tests with clinically significant abnormalities unrelated to neurocysticercosis or its treatment.

ADDITIONAL EXCLUSION CRITERIA FOR HEALTHY SUBJECTS:

Laboratory tests with clinically significant abnormalities.

A history of brain disease.

The usage of nonsteroidal and other anti-inflammatory medications is not an exclusion criterion.

04

Study design

Phase
Phase 1
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Interventions

  • Drug[C-11]PBR28
05

What researchers measure

Primary outcomes

  1. Binding of [C-11]PBR28 at peripheral benzodiazepine receptors

Secondary outcomes

  1. MRI

    Time frame: years

06

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
07

References and documents

Publications

  • Anholt RR, De Souza EB, Oster-Granite ML, Snyder SH. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats. J Pharmacol Exp Ther. 1985 May;233(2):517-26. PubMed 2987488 ↗
  • Anholt RR, Murphy KM, Mack GE, Snyder SH. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves. J Neurosci. 1984 Feb;4(2):593-603. doi: 10.1523/JNEUROSCI.04-02-00593.1984. PubMed 6321699 ↗
  • Anholt RR, Pedersen PL, De Souza EB, Snyder SH. The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. J Biol Chem. 1986 Jan 15;261(2):576-83. PubMed 3001071 ↗
  • 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. PubMed 29749279 ↗
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Registry details

Key details

Study ID
NCT00526916
Lead sponsor
National Institute of Mental Health (NIMH)
Responsible party
Sponsor
First posted
Sep 10, 2007
Start date
Sep 4, 2007
Completion
Sep 5, 2014
Last update
Dec 12, 2019

Study contacts

Masahiro Fujita, M.D.
principal investigator · National Institute of Mental Health (NIMH)
View the source record on ClinicalTrials.gov ↗

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