Cerebrovascular Reactivity and Oxygen Metabolism as Markers of Neurodegeneration After Traumatic Brain Injury

NCT ID: NCT04820881

Last Updated: 2022-04-27

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

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-10-01

Study Completion Date

2024-09-30

Brief Summary

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This grant award entitled, "Cerebrovascular Reactivity and Oxygen Metabolism as Markers for Neurodegeneration after Traumatic Brain Injury" (hereafter, "Neurovascular Study"), aims to determine if neurovascular contributors to neurodegeneration can serve as markers of the emergence or progression of degenerative processes after traumatic brain injury in middle-aged and older adults.

Detailed Description

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This grant award entitled, "Cerebrovascular Reactivity and Oxygen Metabolism as Markers for Neurodegeneration after Traumatic Brain Injury" (hereafter, "Neurovascular Study"), aims to determine if neurovascular contributors to neurodegeneration can serve as markers of the emergence or progression of degenerative processes after traumatic brain injury in middle-aged and older adults. Primary outcomes are cerebrovascular reactivity (CVR), as measured by functional Magnetic Resonance Imaging (MRI) Blood Oxygen Level Dependent (BOLD) and cerebral metabolic rate of oxygen (CMRO2) as assessed by the novel MRI sequence called, "T-2 Relaxation-Under-Spin-Tagging" (TRUST). After the baseline primary endpoints are acquired, a single dose of sildenafil 50mg will be given to assess for the effects of a hypercapnia task on CVR and CMRO2. Other outcomes measured include additional imaging sequences (diffusion, ASL), volumetric analysis, and neuropsychological tests.

Conditions

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Neurodegenerative Diseases

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Case Group

Measurement of cerebrovascular reactivity and oxygen metabolism before and after a single dose of 50mg sildenafil citrate. Diffusion tensor imaging, other structural imaging and cognitive testing will also be completed.

No interventions assigned to this group

Control Group

Measurement of cerebrovascular reactivity and oxygen metabolism before and after a single dose of 50mg sildenafil citrate. Diffusion tensor imaging, other structural imaging and cognitive testing will also be completed.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Ages 50-80 years
* Eligible for Washington, DC Veterans Affairs Medical Center (VAMC) research participation
* Capacity to provide consent to participate in research (assessment made by study neurologist and PI)
* Ability to read and write English


• History of traumatic brain injury of sufficient severity to have resulted in medical attention ascertained via the Ohio State University TBI Identification Questionnaire (OSU TBI-ID). TBI defined by Departments of Defense/Veterans Affairs (DoD/VA) criteria.


• No history of traumatic brain injury of sufficient severity to have resulted in medical attention ascertained via the OSU TBI-ID, and no TBI based upon DOD/VA criteria.

Exclusion Criteria

* History of penetrating brain injury
* History or evidence of disabling neurological or psychiatric condition such as epilepsy (besides posttraumatic epilepsy), multiple sclerosis, hypoxic-ischemic encephalopathy, encephalitis, or schizophrenia
* History or evidence of cortical or subcortical stroke
* History or evidence of diabetes mellitus requiring therapy (Hemoglobin A1c \> 9.0% for purposes of this study)
* History or evidence of uncontrolled hyperlipidemia. For the purposes of this study, "hyperlipidemia" will be defined as total cholesterol of 230 in the presence of either or both diabetes and hypertension and 300 in the absence of both of these conditions.

Statin therapy with normal cholesterol levels is allowed.

* History or evidence of uncontrolled hypertension (defined as systolic pressure \> 160 and/or diastolic pressure \> 110 mmHg), or hypotension (systolic pressure \< 110 and/or diastolic pressure \< 65 mmHg). Hypertension controlled with a single anti- hypertensive medication is allowed.
* Untreated atrial fibrillation
* Active tobacco use
* MRI incompatibility
* If a participant is currently or has previously taken a phosphodiesterase inhibitor (PDESi), then a two week washout period is required immediately prior to the evaluation visit.
* Use of nitrates
Minimum Eligible Age

50 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Henry M. Jackson Foundation for the Advancement of Military Medicine

OTHER

Sponsor Role collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role lead

Responsible Party

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Julie C. Chapman

Neuroscientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Julie C Chapman, PsyD

Role: PRINCIPAL_INVESTIGATOR

Washington, DC VAMC

Locations

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Washington, DC Veterans Affairs Medical Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Julie C Chapman, PsyD

Role: CONTACT

202-745-8000 ext. 55024

Facility Contacts

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Julie C Chapman, PsyD

Role: primary

202-745-8000 ext. 55024

Marshall S Balish, MD, PhD

Role: backup

202.745.8148

Other Identifiers

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MIRB01897

Identifier Type: -

Identifier Source: org_study_id

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