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

NCT ID: NCT00526916

Last Updated: 2019-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-04

Study Completion Date

2014-09-05

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Neurocysticercosis Healthy

Keywords

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Epilepsy Taenia Solium Microglia Neuroinflammation Compartment Model Neurocysticercosis Healthy Volunteer HV

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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[C-11]PBR28

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Common to patients with neurocysticercosis and healthy subjects:

Ages between 18 and 75, inclusive.


CONTROL SUBJECTS:

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

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.


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.


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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Masahiro Fujita, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Mental Health (NIMH)

Locations

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National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 2987488 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6321699 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3001071 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29749279 (View on PubMed)

Other Identifiers

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07-M-0208

Identifier Type: -

Identifier Source: secondary_id

070208

Identifier Type: -

Identifier Source: org_study_id