Clinical trial NCT04820881: Cerebrovascular Reactivity and Oxygen Metabolism as Markers of Neurodegeneration After Traumatic Brain Injury
Official title: Cerebrovascular Reactivity and Oxygen Metabolism as Markers of Neurodegeneration After Traumatic Brain Injury
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neurodegenerative Diseases
Lead sponsor: Washington D.C. Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: Henry M. Jackson Foundation for the Advancement of Military Medicine
First posted: 2021-03-29
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Middle-aged and older adults with previous head injury experiencing current neurodegeneration.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria (All Participants):

* 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

Inclusion Criteria Case Group:

• 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.

Inclusion Criteria Control Group:

• 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 (All Participants):

* 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

Primary outcomes:
measure: Cerebrovascular Reactivity (CVR)
timeFrame: Two years
measure: Cerebral Metabolic Rate of Oxygen (CMRO2)
timeFrame: Two years
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington, DC Veterans Affairs Medical Center
state: District of Columbia
Study officials:
affiliation: Washington, DC VAMC
name: Julie C Chapman, PsyD
role: PRINCIPAL_INVESTIGATOR
References: