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Asymptomatic Carotid Stenosis and Mobility Function With Exercise Intervention (ACCOF-Ex)

Primary Purpose

Asymptomatic Carotid Stenosis (50-69%), Mobility Impairment

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise Intervention
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asymptomatic Carotid Stenosis (50-69%) focused on measuring Asymptomatic carotid stenosis

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Eligible patients will be at least 18 years of age and will have asymptomatic 50-69% carotid stenosis
  • Asymptomatic status will be confirmed as in NIH trials on asymptomatic carotid stenosis, by medical history, physical examination, and the National Institutes of Health Stroke Scale (NIHSS)
  • Stenosis severity will be determined by duplex sonography, MR angiography, or CT angiography

Exclusion Criteria:

  • previous stroke or transient ischemic attack
  • occlusion or severe stenosis of the non-index carotid artery
  • planned carotid revascularization
  • persons advised by their doctor not to exercise
  • a medical condition that precludes the ability to ambulate
  • exercise or reduces the likelihood of follow-up
  • evidence of a medical condition that would lead to an increased risk of accident, injury, or illness as a result of the proposed testing or intervention
  • orthostatic hypotension
  • severe medical illness that interferes with the evaluation of outcomes
  • uncorrected visual impairment or eye surgery in the past 6 months
  • patients that are unable to undergo PW-MRI due to gadolinium contrast allergy or renal insufficiency will also be excluded
  • given the possibility that comorbid cognitive impairment may influence balance and mobility function, subjects with any documented medical history of dementia or cognitive impairment or those unable to follow commands will be excluded from the study
  • In addition, subjects with other neurological conditions such as Parkinson's, peripheral neuropathy or myopathy, sedative medications, and major depression (Center for Epidemiological Studies Depression Survey Score >16) will be excluded
  • in order to avoid ceiling effects of the Mini BESTest, potential subjects will be prescreened for balance dysfunction using a 10-second Single Leg Stance Test

    • those that are able to complete the test without losing balance on either side will be excluded from the study
  • the investigators will exclude subjects that participate in structured aerobic exercise routinely greater than three times per week within a month of starting the study

Sites / Locations

  • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MDRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control

Exercise Intervention

Arm Description

The control group will undergo standard-of-care vascular risk factor modification. Control participants will be contacted via telephone on a weekly basis to discuss the importance of vascular risk factor management and adherence to prescribed medical management.

The exercise intervention group will undergo 12 weeks of AeroBal exercise training (approximately 3 times/week). Each exercise session will consist of a 5-minute warm-up walk, approximately 30 minutes of aerobic exercise at a goal of 60-75% HRmax, 15 minutes of balance exercises, and a 5-minute cool-down walk.

Outcomes

Primary Outcome Measures

Change in Mini BESTest score
The Mini BESTest is a reliable and valid measure of balance and mobility that is sensitive to changes in individuals with balance dysfunction, and has age-related normative values. It will be the primary outcome measure to evaluate changes in balance and mobility following exercise intervention. The Mini BESTest includes fourteen items that evaluate the following: anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait.

Secondary Outcome Measures

Change in secondary mobility measures (Four square step test [FSST])
The FSST assesses dynamic mobility by timing patients while they quickly step over an object (i.e., canes) while moving forward, laterally, and backward. The score is based on time take to complete the task (seconds). The FSST was chosen because it has excellent reliability, normative values, and scores are predictive of falls in older adults.
Change in time to peak (TTP) delay on perfusion-weighted MRI
TTP is a perfusion-weighted magnetic resonance imaging (PW-MRI) measure that quantifies the delay in time taken for contrast to reach maximum concentration. The difference between the TTP measurements of the ipsilateral and contralateral hemispheres will be calculated to arrive at the TTP delay. TTP delay has low inter-observer and inter-scan variability, and is sensitive to early perfusion impairment.
Secondary measures of cerebral perfusion (breath-holding index [BHI])
Transcranial Doppler is non-invasive, readily available, does not utilize contrast, and allows for quantification of cerebral vasoreactivity via a breath-holding index (BHI). A BHI of <0.69 indicates impaired cerebrovascular hemodynamics.
Change in secondary mobility measures (Walking while talking test [WWT])
The WWT Test is a dual-task interference test that measures divided attention to assess cognitive-motor interactions. Participants will be asked to walk while reciting the alphabet aloud (WWT-simple) and while reciting alternate letters of the alphabet aloud (WWT-complex). The score is based on time taken to complete the task. The WWT Test is responsive to change after exercise intervention in older adults, associated with perceived physical function, and predictive of falls.
Secondary measures of cerebral perfusion (functional near infrared spectroscopy [fNIRS])
fNIRS is a novel imaging technology that measures cerebral hemodynamic responses by using the absorption of near-infrared light to identify changes in oxy- and deoxy- hemoglobin concentrations evoked by neural activity, otherwise known as neurovascular coupling. Change in oxyhemoglobin concentrations measured during tasks at baseline and 12 weeks will be compared.

Full Information

First Posted
June 16, 2022
Last Updated
November 23, 2022
Sponsor
VA Office of Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT05436600
Brief Title
Asymptomatic Carotid Stenosis and Mobility Function With Exercise Intervention
Acronym
ACCOF-Ex
Official Title
Asymptomatic Carotid Stenosis and Mobility Function With Exercise Intervention
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
September 30, 2027 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Moderate (50-69%) asymptomatic carotid artery stenosis (ACAS) is an important and under-appreciated contributor to balance and mobility dysfunction. This is significant because declines in balance and mobility are a significant predictor of falls, disability, loss of independence, and death in older adults. Further, falls and fall-related injuries in older adults cost approximately 50 billion dollars annually in the United States, and are the leading cause of adverse events reported by the Veterans Health Administration. This proposal seeks to: 1) investigate the impact of a supervised aerobic and challenging balance exercise program on balance and mobility function in patients with moderate ACAS; and 2) elucidate whether these changes are related to changes in cerebral perfusion. With 830,000 Veterans estimated to have moderate ACAS and at risk for balance and mobility dysfunction and increased falls, the findings from this study could have significant impacts on the clinical management, quality of life, and functional independence of Veterans with moderate ACAS.
Detailed Description
The investigators will conduct a prospective randomized controlled trial designed to evaluate the effects of a supervised aerobic and challenging balance exercise (AeroBal) program on balance and mobility function (primary outcome), and fall risk and physical function (secondary outcomes) in patients with moderate ACAS. The investigators hypothesize that aerobic and challenging balance exercises will lead to greater improvement in balance and mobility function, de-creased fall risk, and improved perceived physical function in patients with moderate ACAS compared to standard-of-care vascular risk-factor reduction alone. Patients will undergo 1:1 blocked randomization on sex into either the exercise training group plus standard-of-care or the control group undergoing standard-of-care vascular risk-factor modification alone. To account for attrition, the investigators aim to enroll a total of 50 patients and anticipate completing the study with 34 patients. Baseline demographic data, medical history, balance and mobility function, physical function, cerebral perfusion (PW-MRI and fNIRS) and vasoreactivity (TCD) will be collected on all patients. The exercise training group will perform 12 weeks of supervised aerobic and balance exercises. In order to maintain consistency in contact between the clinical research team and the control subjects versus the intervention group, control participants will be contacted via telephone on a weekly basis to discuss the importance of vascular risk factor management and adherence to prescribed medical management. To assess the change in outcome measures, the investigators will repeat measurements in both groups at 6- and 12-weeks. PW-MRI will only be performed at the 12-week visit to minimize patient risk and contain costs. The primary outcome measure (change in Mini BESTest score) and secondary measures (fall rate and physical function) for Aim 1, and the primary outcome measure (TTP on PW-MRI) and secondary outcome measures (BHI on TCD and change in oxy-hemoglobin concentration on fNIRS) for Aim 2 will be analyzed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asymptomatic Carotid Stenosis (50-69%), Mobility Impairment
Keywords
Asymptomatic carotid stenosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients will undergo 1:1 blocked randomization on sex into either the exercise training group plus standard-of-care or the control group undergoing standard-of-care vascular risk-factor modification with weekly contact by the study team.
Masking
Outcomes Assessor
Masking Description
The outcomes assessor will be masked to group assignment.
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm Description
The control group will undergo standard-of-care vascular risk factor modification. Control participants will be contacted via telephone on a weekly basis to discuss the importance of vascular risk factor management and adherence to prescribed medical management.
Arm Title
Exercise Intervention
Arm Type
Experimental
Arm Description
The exercise intervention group will undergo 12 weeks of AeroBal exercise training (approximately 3 times/week). Each exercise session will consist of a 5-minute warm-up walk, approximately 30 minutes of aerobic exercise at a goal of 60-75% HRmax, 15 minutes of balance exercises, and a 5-minute cool-down walk.
Intervention Type
Other
Intervention Name(s)
Exercise Intervention
Other Intervention Name(s)
AeroBal exercise intervention
Intervention Description
The exercise intervention group will undergo 12 weeks of AeroBal exercise training (approximately 3 times/week). Each exercise session will consist of a 5-minute warm-up walk, approximately 30 minutes of aerobic exercise at a goal of 60-75% HRmax, 15 minutes of balance exercises, and a 5-minute cool-down walk.
Primary Outcome Measure Information:
Title
Change in Mini BESTest score
Description
The Mini BESTest is a reliable and valid measure of balance and mobility that is sensitive to changes in individuals with balance dysfunction, and has age-related normative values. It will be the primary outcome measure to evaluate changes in balance and mobility following exercise intervention. The Mini BESTest includes fourteen items that evaluate the following: anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait.
Time Frame
Baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Change in secondary mobility measures (Four square step test [FSST])
Description
The FSST assesses dynamic mobility by timing patients while they quickly step over an object (i.e., canes) while moving forward, laterally, and backward. The score is based on time take to complete the task (seconds). The FSST was chosen because it has excellent reliability, normative values, and scores are predictive of falls in older adults.
Time Frame
Baseline to 12 weeks
Title
Change in time to peak (TTP) delay on perfusion-weighted MRI
Description
TTP is a perfusion-weighted magnetic resonance imaging (PW-MRI) measure that quantifies the delay in time taken for contrast to reach maximum concentration. The difference between the TTP measurements of the ipsilateral and contralateral hemispheres will be calculated to arrive at the TTP delay. TTP delay has low inter-observer and inter-scan variability, and is sensitive to early perfusion impairment.
Time Frame
Baseline to 12 weeks
Title
Secondary measures of cerebral perfusion (breath-holding index [BHI])
Description
Transcranial Doppler is non-invasive, readily available, does not utilize contrast, and allows for quantification of cerebral vasoreactivity via a breath-holding index (BHI). A BHI of <0.69 indicates impaired cerebrovascular hemodynamics.
Time Frame
Baseline to 12 weeks
Title
Change in secondary mobility measures (Walking while talking test [WWT])
Description
The WWT Test is a dual-task interference test that measures divided attention to assess cognitive-motor interactions. Participants will be asked to walk while reciting the alphabet aloud (WWT-simple) and while reciting alternate letters of the alphabet aloud (WWT-complex). The score is based on time taken to complete the task. The WWT Test is responsive to change after exercise intervention in older adults, associated with perceived physical function, and predictive of falls.
Time Frame
Baseline to 12 weeks
Title
Secondary measures of cerebral perfusion (functional near infrared spectroscopy [fNIRS])
Description
fNIRS is a novel imaging technology that measures cerebral hemodynamic responses by using the absorption of near-infrared light to identify changes in oxy- and deoxy- hemoglobin concentrations evoked by neural activity, otherwise known as neurovascular coupling. Change in oxyhemoglobin concentrations measured during tasks at baseline and 12 weeks will be compared.
Time Frame
Baseline to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Eligible patients will be at least 18 years of age and will have asymptomatic 50-69% carotid stenosis Asymptomatic status will be confirmed as in NIH trials on asymptomatic carotid stenosis, by medical history, physical examination, and the National Institutes of Health Stroke Scale (NIHSS) Stenosis severity will be determined by duplex sonography, MR angiography, or CT angiography Exclusion Criteria: previous stroke or transient ischemic attack occlusion or severe stenosis of the non-index carotid artery planned carotid revascularization persons advised by their doctor not to exercise a medical condition that precludes the ability to ambulate exercise or reduces the likelihood of follow-up evidence of a medical condition that would lead to an increased risk of accident, injury, or illness as a result of the proposed testing or intervention orthostatic hypotension severe medical illness that interferes with the evaluation of outcomes uncorrected visual impairment or eye surgery in the past 6 months patients that are unable to undergo PW-MRI due to gadolinium contrast allergy or renal insufficiency will also be excluded given the possibility that comorbid cognitive impairment may influence balance and mobility function, subjects with any documented medical history of dementia or cognitive impairment or those unable to follow commands will be excluded from the study In addition, subjects with other neurological conditions such as Parkinson's, peripheral neuropathy or myopathy, sedative medications, and major depression (Center for Epidemiological Studies Depression Survey Score >16) will be excluded in order to avoid ceiling effects of the Mini BESTest, potential subjects will be prescreened for balance dysfunction using a 10-second Single Leg Stance Test those that are able to complete the test without losing balance on either side will be excluded from the study the investigators will exclude subjects that participate in structured aerobic exercise routinely greater than three times per week within a month of starting the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarasijhaa K Desikan, MD
Phone
(410) 605-7000
Email
sdesikan@som.umaryland.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kimberlly A Nordstrom
Phone
(410) 706-3941
Email
kimberlly.nordstrom@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarasijhaa K Desikan, MD
Organizational Affiliation
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frederick M Ivey, PhD
Phone
410-605-7000
Ext
56510
Email
Frederick.Ivey@va.gov
First Name & Middle Initial & Last Name & Degree
Natalie V Dugger, BS
Phone
(410) 605-7000
Ext
56407
Email
Natalie.Dugger@va.gov
First Name & Middle Initial & Last Name & Degree
Sarasijhaa K Desikan, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Asymptomatic Carotid Stenosis and Mobility Function With Exercise Intervention

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