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PiB PET Scanning in Speech and Language Based Dementias

Primary Purpose

PPA, Primary Progressive Aphasia, Aphasia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
C-11 PiB
F-18 FDG
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for PPA focused on measuring aphasia, apraxia of speech, language

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Over the age of 18
  • Has an informant/study partner who will be able to provide independent evaluation of functioning
  • Speaks English as their primary language (including bilingual patients whose primary language is English)
  • Fulfills diagnostic criteria for PPA (Primary Progressive Aphasia) or Progressive Apraxia of Speech
  • Agrees to and is eligible to undergo MRI and PET scanning
  • If woman of child bearing age, pt must agree to pregnancy test no more than 48 hours before the PET scans

Exclusion Criteria:

  • Any concurrent illnesses that could account for speech and language deficits, such as:

    • traumatic brain injury, strokes and developmental syndromes
    • patients meeting criteria for another neurodegenerative disease (Alzheimer's Disease, Dementia with Lewy Bodies, behavioral variant frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration)
  • Women who is pregnant or post-partum and breast-feeding
  • Patients for which MRI is contraindicated (metal in head, cardiac pace maker, etc.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism,(e.g. chemotherapy)
  • Patient is mute (secondary to dysarthria only)

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PiB and FDG positron emission tomography (PET)

Arm Description

All subjects will receive PiB and FDG PET diagnosis on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.

Outcomes

Primary Outcome Measures

Percentage of patients with different speech and language based dementia (SLD) subtypes who have a [N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positive positron emission tomography (PET) scan at presentation

Secondary Outcome Measures

Percentage of patients who exhibit apraxia of speech as measured by the Apraxia of Speech Rating Scale at presentation
Apraxia of Speech Rating Scale has been developed by the speech pathologists involved in this study, and has tested to be reliable. The scale ranges from 0-4; 0=apraxia of speech not present, 4=apraxia of speech nearly always evident and marked in severity.
Temporoparietal hypometabolism as shown on [18-F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan at presentation
Grey matter loss as shown on magnetic resonance imaging (MRI) at presentation

Full Information

First Posted
June 7, 2012
Last Updated
December 21, 2015
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT01623284
Brief Title
PiB PET Scanning in Speech and Language Based Dementias
Official Title
PiB PET Scanning in Speech and Language Based Dementias
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is designed to determine whether there are clinical features that can be used as biomarkers to predict whether underlying Alzheimer's pathology is the cause of a speech and language based dementia. The primary hypothesis is that the proportion of patients who test positive for beta-amyloid deposition will vary across different speech and language based dementias.
Detailed Description
Speech and language based dementias (SLDs) (often referred to as primary progressive aphasias or PPA) are neurodegenerative diseases in which speech or language impairments are the most salient features of the disease and explain deficits in activities of daily living. Patients with SLDs may have poor grammar, prominent anomia, comprehension deficits, speech production and articulation problems, difficulty with repetition of words or sentences, word finding pauses, or a combination of all these features. The SLDs can be further divided into different subtypes. Up to 50% of patients with SLDs that go on to autopsy have shown Alzheimer type pathology where beta-amyloid deposition is observed; the rest have pathology consistent with frontotemporal lobar degeneration where beta-amyloid deposition is absent. Future disease modifying treatments that target beta-amyloid will most likely differ from treatments that do not target beta-amyloid. As a consequence, biomarkers are needed to differentiate patients with SLDs with and without beta-amyloid deposition. Little research has been done to identify biomarkers that could differentiate patients with SLDs with and without beta-amyloid, mainly because the gold standard to identify the presence of beta-amyloid has been pathological examination, which does not always occur, and may not occur until more than 10 years after onset. The recent development of [N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole also known as 11C Pittsburgh Compound B or PiB is a solution to this problem since PiB allows the in vivo detection of beta-amyloid. Unfortunately, PiB is very expensive. The long term goal of our research is to develop a cost effective algorithmic approach to the evaluation and diagnosis of patients presenting with SLDs. The objective of the studies outlined in this proposal is to identify clinical, neuropsychological, or imaging biomarkers that are readily available, relatively inexpensive, and non-invasive that will allow the differentiation of patients with SLDs with and without beta-amyloid deposition. We will use PiB as an indicator of beta-amyloid pathology. Our proposal is predicated upon our strong preliminary data showing that clinical, neuropsychological and radiological features differ between patients with SLDs with and without beta-amyloid deposition. Our central hypothesis is that temporo-parietal lobe findings such as memory loss, visuospatial/perceptual impairment, parietal lobe atrophy on magnetic resonance imaging (MRI), and parietal lobe hypometabolism on [18-F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET), will be associated with beta-amyloid deposition (PiB positive status). On-the-other hand, frontal lobe features, such as apraxia of speech and behavioral and executive dysfunction, as well as extrapyramidal features such as Parkinsonism, will be associated with absence of beta-amyloid deposition (PiB negative status). The rationale for examining these clinical-imaging relationships is that successful predictions will provide a solid scientific foundation for the ultimate development of a cost effective algorithm to guide the diagnosis of SLDs. Patients found to be eligible and willing to enroll in this study will be asked to undergo a Neurologic Examination, a Speech Pathology Consultation, Neuropsychometric testing, an MRI scan, an FDG PET scan and a PiB PET scan of the brain. This will be done over a period of two days at the Mayo Clinic in Rochester, MN.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PPA, Primary Progressive Aphasia, Aphasia, Non-fluent Aphasia, Semantic Dementia, Apraxia of Speech, Primary Progressive Nonfluent Aphasia, Progressive Aphasia
Keywords
aphasia, apraxia of speech, language

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
168 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PiB and FDG positron emission tomography (PET)
Arm Type
Experimental
Arm Description
All subjects will receive PiB and FDG PET diagnosis on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.
Intervention Type
Drug
Intervention Name(s)
C-11 PiB
Other Intervention Name(s)
Pittsburgh Compound B
Intervention Description
One time intravenous administration of 740 megabecquerel (MBq) of [N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).
Intervention Type
Drug
Intervention Name(s)
F-18 FDG
Other Intervention Name(s)
Fluorodeoxyglucose-18
Intervention Description
One time intravenous administration of 629 megabecquerel (MBq) of [18-F]-fluoro-deoxy-glucose (FDG) (range 555 - 740 MBq).
Primary Outcome Measure Information:
Title
Percentage of patients with different speech and language based dementia (SLD) subtypes who have a [N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positive positron emission tomography (PET) scan at presentation
Time Frame
Study entry, approximately day 1 or day 2 of study
Secondary Outcome Measure Information:
Title
Percentage of patients who exhibit apraxia of speech as measured by the Apraxia of Speech Rating Scale at presentation
Description
Apraxia of Speech Rating Scale has been developed by the speech pathologists involved in this study, and has tested to be reliable. The scale ranges from 0-4; 0=apraxia of speech not present, 4=apraxia of speech nearly always evident and marked in severity.
Time Frame
Study entry, approximately day 1 or day 2 of study
Title
Temporoparietal hypometabolism as shown on [18-F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan at presentation
Time Frame
Study entry, approximately day 1 or day 2 of study
Title
Grey matter loss as shown on magnetic resonance imaging (MRI) at presentation
Time Frame
Study entry, approximately day 1 or day 2 of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Over the age of 18 Has an informant/study partner who will be able to provide independent evaluation of functioning Speaks English as their primary language (including bilingual patients whose primary language is English) Fulfills diagnostic criteria for PPA (Primary Progressive Aphasia) or Progressive Apraxia of Speech Agrees to and is eligible to undergo MRI and PET scanning If woman of child bearing age, pt must agree to pregnancy test no more than 48 hours before the PET scans Exclusion Criteria: Any concurrent illnesses that could account for speech and language deficits, such as: traumatic brain injury, strokes and developmental syndromes patients meeting criteria for another neurodegenerative disease (Alzheimer's Disease, Dementia with Lewy Bodies, behavioral variant frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration) Women who is pregnant or post-partum and breast-feeding Patients for which MRI is contraindicated (metal in head, cardiac pace maker, etc.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism,(e.g. chemotherapy) Patient is mute (secondary to dysarthria only)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith A Josephs, M.D. MST, MSc
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials

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PiB PET Scanning in Speech and Language Based Dementias

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