Tau Imaging of Chronic Traumatic Encephalopathy

• ClinicalTrials.gov Identifier: NCT02191267
• Recruitment Status: Completed
• First Posted: July 16, 2014
• Results First Posted: May 17, 2018
• Last Update Posted: May 17, 2018
• Sponsor: Brigham and Women's Hospital
• Collaborators: U.S. Army Medical Research and Development Command; Boston University
• Information provided by (Responsible Party): Martha E Shenton, Brigham and Women's Hospital

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Chronic Traumatic Encephalopathy
• Interventions: Radiation: [F18]-T807; Radiation: [F18]-Florbetapir; Device: MRI/MRS; Genetic: Genetic Analysis for Genetic Risk Score for Tau.
• Enrollment: 30

Participant Flow

Recruitment Details	24 subjects at presumed risk for Chronic Traumatic Encephalopathy (CTE), 6 healthy control subjects without a history of repetitive brain trauma, and 4 Alzheimer's Disease (AD) subjects were recruited from the Boston University Center for the study of Chronic Traumatic Encephalopathy.
Pre-assignment Details	Subjects were pre-assigned according to previously assigned study diagnostic status based on prior participation in studies at the Boston Center for the study of Chronic Traumatic Encephalopathy.

Arm/Group Title	Presumed CTE Group	Control Group	AD Dementia Group
Arm/Group Description	Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Period Title: Overall Study
Started	20	6	4
Completed	19	6	4
Not Completed	1	0	0
Reason Not Completed
Withdrawal by Subject	1	0	0

Baseline Characteristics

Arm/Group Title		Presumed CTE Group	Control Group	AD Dementia Group	Total
Arm/Group Description		Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Total of all reporting groups
Overall Number of Baseline Participants		19	6	4	29
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	6 participants	4 participants	29 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	19 100.0%	6 100.0%	4 100.0%	29 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	6 participants	4 participants	29 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	19 100.0%	6 100.0%	4 100.0%	29 100.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	6 participants	4 participants	29 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	6 31.6%	1 16.7%	0 0.0%	7 24.1%
	White	13 68.4%	5 83.3%	4 100.0%	22 75.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	19 participants	6 participants	4 participants	29 participants
		19	6	4	29

Outcome Measures

1. Primary Outcome

Title	Tau Protein Uptake..
Description	Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr). Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes. SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.
Time Frame	Day 1 - of 2 day study.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Presumed CTE Group	Control Group	AD Dementia Group
Arm/Group Description:	Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Overall Number of Participants Analyzed	19	6	4
Mean (Standard Deviation); Unit of Measure: SUVr
	1.1871 (0.0762)	1.1652 (0.0670)	1.5910 (0.3807)

2. Secondary Outcome

Title	Beta-Amyloid (Aβ) Protein Uptake.
Description	Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions. Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir. SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.
Time Frame	Day 2 - of 2 day study.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Presumed CTE Group	Control Group	AD Dementia Group
Arm/Group Description:	Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Overall Number of Participants Analyzed	19	6	4
Mean (Standard Deviation); Unit of Measure: SUVr
Posterior Cingulate	1.346 (0.215)	1.290 (0.068)	1.760 (0.352)
Superior Parietal	1.225 (0.180)	1.118 (0.073)	1.708 (1.708)
Lateral Frontal	1.196 (0.178)	1.145 (0.085)	1.728 (0.291)
Medial Frontal	1.253 (0.190)	1.182 (0.083)	1.847 (0.261)
Lateral Temporal	1.178 (0.164)	1.113 (0.083)	1.766 (0.345)
Occipital	1.288 (0.191)	1.157 (0.039)	1.540 (1.540)

Adverse Events

Time Frame	Through study completion, Subjects were assessed for adverse effects immediately following each scan (On Day 1 and Day 2) and again by telephone 72 hours following study participation. Thus, assessment for adverse events were made over over a 5-day period which included Days 1 and 2 of the study visit and a follow-up telephone assessment on Day 5.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Presumed CTE Group	Control Group	AD Dementia Group
Arm/Group Description	Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.	Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan. [F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain. [F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
All-Cause Mortality
	Presumed CTE Group	Control Group	AD Dementia Group
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	0/6 (0.00%)	0/4 (0.00%)
Serious Adverse Events
	Presumed CTE Group	Control Group	AD Dementia Group
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	0/6 (0.00%)	0/4 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Presumed CTE Group	Control Group	AD Dementia Group
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	0/6 (0.00%)	0/4 (0.00%)

Limitations and Caveats

Exploratory aims including potential MRI and MRS biomarkers and genetic analysis for genetic risk score for Tau will also be analyzed but are not primary or secondary outcome measures.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Martha Shenton
• Organization: Brigham and Women's Hospital
• Phone: 617-699-6152
• EMail: shenton@bwh.harvard.edu

Publications:

Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.

Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.

• Responsible Party: Martha E Shenton, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT02191267
• Other Study ID Numbers: 2014P000035
• First Submitted: July 15, 2014
• First Posted: July 16, 2014
• Results First Submitted: March 15, 2018
• Results First Posted: May 17, 2018
• Last Update Posted: May 17, 2018