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

April 25, 2022 updated by: Julie C. Chapman, Washington D.C. Veterans Affairs Medical Center
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.

Study Overview

Status

Recruiting

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.

Study Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • District of Columbia
      • Washington, District of Columbia, United States, 20422
        • Recruiting
        • Washington, DC Veterans Affairs Medical Center
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Middle-aged and older adults with previous head injury experiencing current neurodegeneration.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cerebrovascular Reactivity (CVR)
Time Frame: Two years
Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasoactive stimulus, in this case hypercapnia induced by 5% carbon dioxide as measured by MRI BOLD
Two years
Cerebral Metabolic Rate of Oxygen (CMRO2)
Time Frame: Two years
Cerebral metabolic rate of oxygen represents the amount of oxygen consumed as measured by the MRI T2-Relaxation-Under-Spin-Tagging (TRUST) sequence.
Two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Julie C Chapman, PsyD, Washington, DC VAMC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2021

Primary Completion (ANTICIPATED)

September 1, 2024

Study Completion (ANTICIPATED)

September 1, 2024

Study Registration Dates

First Submitted

March 24, 2021

First Submitted That Met QC Criteria

March 26, 2021

First Posted (ACTUAL)

March 29, 2021

Study Record Updates

Last Update Posted (ACTUAL)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 25, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The grant that funds this study requires that de-identified data be submitted annually to the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System, of which the Department of Veterans Affairs is part. The FITBIR database, maintained by the National Institutes of Health, allows other researchers studying traumatic brain injury to apply for approval to utilize this previously collected, de-identified data for qualified research projects. Only de-identified data, which does not include anything that might directly identify participants, will be shared with FITBIR users who have been approved for research use.

IPD Sharing Time Frame

Time frame specified by the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics Program.

IPD Sharing Access Criteria

Access criteria specified by the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics Program.

IPD Sharing Supporting Information Type

  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neurodegenerative Diseases

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