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Reshaping the Path of Vascular Cognitive Impairment (VCI)

Primary Purpose

Transient Ischemic Attack, Vascular Cognitive Impairment, Subcortical Vascular Dementia

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Resistance exercise training
Control: stretching and relaxation program
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transient Ischemic Attack

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI -- the presence of both cognitive impairment and small vessel ischaemic disease.

Specifically, individuals must meet the following inclusion criteria:

  1. Montreal Cognitive Assessment (MoCA) score less than 26 at screening;
  2. MMSE score of = or > 20 at screening;
  3. Community-dwelling;
  4. Lives in Metro Vancouver;
  5. Able to comply with scheduled visits, treatment plan, and other trial procedures;
  6. Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity;
  7. Stable on a fixed dose of cognitive medications (e.g., donepezil, galantamine, rivastigmine, memantine, etc.) that is not expected to change during the 12-month study period, or, if they are not on any of these medications, they are not expected to start them during the 12-month study period;
  8. Provide a personally signed and dated informed consent document indicating that the individual (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. In addition, an assent form will be provided at baseline and again at regular intervals;
  9. Able to walk independently; and
  10. Must be in sufficient health to participate in study's aerobic-based exercise training program. This will be based on medical history, vital signs, physical examination by study physicians, and written recommendation by family physician indicating individual's appropriateness to participate in an aerobic-based exercise training program.

Exclusion Criteria:

  1. Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or MRI;
  2. Diagnosed with another type of dementia (e.g., AD) or other neurological conditions (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and mobility;
  3. Diagnosed previously with a genetic cause of SIVCI (e.g., CADASIL);
  4. At high risk for cardiac complications during exercise and/or unable to self-regulate activity or to understand recommended activity level (i.e., Class C of the American Heart Risk Stratification Criteria);
  5. Participating in regular RT in the last six months;
  6. Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility;
  7. Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid, etc.); or
  8. Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study.
  9. Unable to meet the specific scanning requirements of the UBC 3T MRI Research Centre. Specifically, we will exclude anyone with: pacemaker, brain aneurysm clip, cochlear implant, recent surgery or tattoos within the past 6 weeks, electrical stimulator for nerves or bones, implanted infusion pump, history of any eye injury involving metal fragments, artificial heart valve, orthopedic hardware, other metallic prostheses, coil, catheter or filter in any blood vessel, ear or eye implant, bullets, or other metallic fragments.

Sites / Locations

  • University of British Columbia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Resistance Training (RT)

Stretching and Relaxation (CON)

Arm Description

The RT program will be a twice-weekly program. A pressurized air system and free weights will be used . The pressurized air system exercises will consist of biceps curls, triceps extension, seated row, latissmus dorsi pull downs, leg press, hamstring curls, and calf raises. Other exercises, with free weights, will include mini-squats, mini-lunges, and lunge walks. The intensity of the training stimulus will initially be at 50% to 60% of 1 repetition maximum (RM) as determined at week two, and progress to 75% to 85% of 1-RM at a work level of 6 to 8 repetitions (2 sets) by week four. The training stimulus will be increased using the 7 RM method. To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of a set of resistance bands of various weights. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and compliance.

The CON program will be a twice-weekly program. The CON group will consist of stretching exercises, basic core-strength/kegal exercises, and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the exercises. To meet the public health mandates of COVID-19, when it is necessary, training will occur at home. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and compliance.

Outcomes

Primary Outcome Measures

Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)
ADAS-Cog 13 Plus additional cognitive tests
Change in white matter health as measured by total white matter lesion volume
White matter hyperintensity volume in mm3

Secondary Outcome Measures

Executive functions as measured by standard neuropsychological tests
Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV)
Cardiometabolic risk factors as measured by blood panel (subset only)
Cardiometabolic risk factors as measured by body mass index
Cardiometabolic risk factors as measured by waist to hip ratio
Physiological falls risk as measured by the Physiological Profile Assessment
Mobility and balance as measured by the Short Physical Performance Battery
Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
Quality of life as measured by the Medical Outcomes Study Short Form-6D (SF-6D)
White matter integrity as measured by diffusion tensor imaging
Myelin plasticity as measured by multicomponent relaxation imaging
Memory as measured by standard neuropsychological tests
Upper body strength as measured by grip strength
Lower body strength as measured by 30 sec sit to stand test (subset only)
Functional capacity as measured by 6 minute walk test
Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only)
Self-reported physical activity as measured by the PASE questionnaire
NIH Cognitive Toolbox
Isokinetic strength of the lower limb (subset only)
Functional connectivity using resting state fMRI (subset only)
Health resource utilization
Prospective falls via monthly falls calendars
Mobility using timed up and go test
Dual-task ability using dual-task timed up and go test
Dual task gait using Gaitrite mat (subset only)
Cognitive function using ADAS-Cog 13
Dominant quad isometric strength using a strain gauge
Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only)
Regional brain volumes using structural MRI
Selected Pro- and anti-inflammatory cytokines in blood (subset only)
IFN-alpha, IL-1 alpha, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-17, TNF-alpha, Rantes, CXCL1, IL-18, TGF-B
Telomere Length

Full Information

First Posted
January 14, 2016
Last Updated
April 3, 2023
Sponsor
University of British Columbia
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1. Study Identification

Unique Protocol Identification Number
NCT02669394
Brief Title
Reshaping the Path of Vascular Cognitive Impairment (VCI)
Official Title
Reshaping the Path of Vascular Cognitive Impairment With Resistance Training
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
May 17, 2016 (Actual)
Primary Completion Date
June 2, 2022 (Actual)
Study Completion Date
June 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators will conduct a proof-of-concept randomized controlled trial study to provide preliminary evidence of efficacy of a resistance exercise training program for maintaining white matter health and improving cognitive function in older adults with vascular cognitive impairment, defined as the presence of cognitive impairment combined with cerebral small vessel disease, compared with a stretch and relaxation program.
Detailed Description
A total of 88 adults with vascular cognitive impairment will be randomized to either a 12-month twice-weekly resistance training program or stretch and relaxation program. There will be three measurement sessions: baseline, 6 months (midpoint of intervention period), and 12 months (end of intervention period).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transient Ischemic Attack, Vascular Cognitive Impairment, Subcortical Vascular Dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Resistance Training (RT)
Arm Type
Experimental
Arm Description
The RT program will be a twice-weekly program. A pressurized air system and free weights will be used . The pressurized air system exercises will consist of biceps curls, triceps extension, seated row, latissmus dorsi pull downs, leg press, hamstring curls, and calf raises. Other exercises, with free weights, will include mini-squats, mini-lunges, and lunge walks. The intensity of the training stimulus will initially be at 50% to 60% of 1 repetition maximum (RM) as determined at week two, and progress to 75% to 85% of 1-RM at a work level of 6 to 8 repetitions (2 sets) by week four. The training stimulus will be increased using the 7 RM method. To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of a set of resistance bands of various weights. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and compliance.
Arm Title
Stretching and Relaxation (CON)
Arm Type
Active Comparator
Arm Description
The CON program will be a twice-weekly program. The CON group will consist of stretching exercises, basic core-strength/kegal exercises, and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the exercises. To meet the public health mandates of COVID-19, when it is necessary, training will occur at home. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and compliance.
Intervention Type
Behavioral
Intervention Name(s)
Resistance exercise training
Other Intervention Name(s)
RT Program
Intervention Description
Twelve months of twice-weekly resistance training program that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).
Intervention Type
Behavioral
Intervention Name(s)
Control: stretching and relaxation program
Other Intervention Name(s)
CON Program
Intervention Description
Twelve months of twice-weekly stretching and relaxation program that includes stretches, deep breathing and relaxation techniques, general core control exercises, and general posture and health education. Each session will be 60 minutes.
Primary Outcome Measure Information:
Title
Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)
Description
ADAS-Cog 13 Plus additional cognitive tests
Time Frame
Baseline, 6 months, and 12 months
Title
Change in white matter health as measured by total white matter lesion volume
Description
White matter hyperintensity volume in mm3
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Executive functions as measured by standard neuropsychological tests
Time Frame
Baseline, 6 months, and 12 months
Title
Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV)
Time Frame
Baseline and 12 months
Title
Cardiometabolic risk factors as measured by blood panel (subset only)
Time Frame
Baseline, 6 months, and 12 months
Title
Cardiometabolic risk factors as measured by body mass index
Time Frame
baseline, 6 months, and 12 months
Title
Cardiometabolic risk factors as measured by waist to hip ratio
Time Frame
baseline, 6 months, and 12 months
Title
Physiological falls risk as measured by the Physiological Profile Assessment
Time Frame
baseline, 6 months, and 12 months
Title
Mobility and balance as measured by the Short Physical Performance Battery
Time Frame
baseline, 6 months, and 12 months
Title
Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
Time Frame
baseline, 6 months, and 12 months
Title
Quality of life as measured by the Medical Outcomes Study Short Form-6D (SF-6D)
Time Frame
baseline, 6 months, and 12 months
Title
White matter integrity as measured by diffusion tensor imaging
Time Frame
baseline and 12 months
Title
Myelin plasticity as measured by multicomponent relaxation imaging
Time Frame
baseline and 12 months
Title
Memory as measured by standard neuropsychological tests
Time Frame
baseline, 6 months, and 12 months
Title
Upper body strength as measured by grip strength
Time Frame
baseline, 6 months, and 12 months
Title
Lower body strength as measured by 30 sec sit to stand test (subset only)
Time Frame
baseline, 6 months, and 12 months
Title
Functional capacity as measured by 6 minute walk test
Time Frame
Baseline, 6 months, 12 months
Title
Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only)
Time Frame
Baseline, 6 months, 12 months
Title
Self-reported physical activity as measured by the PASE questionnaire
Time Frame
Monthly
Title
NIH Cognitive Toolbox
Time Frame
Baseline, 6 months, 12 months
Title
Isokinetic strength of the lower limb (subset only)
Time Frame
Baseline, 6 months, 12 months
Title
Functional connectivity using resting state fMRI (subset only)
Time Frame
Baseline and 12 months
Title
Health resource utilization
Time Frame
Baseline and every 3 months
Title
Prospective falls via monthly falls calendars
Time Frame
Monthly
Title
Mobility using timed up and go test
Time Frame
Baseline, 6 months, 12 months
Title
Dual-task ability using dual-task timed up and go test
Time Frame
Baseline, 6 months, 12 months
Title
Dual task gait using Gaitrite mat (subset only)
Time Frame
Baseline, 6 months, 12 months
Title
Cognitive function using ADAS-Cog 13
Time Frame
Baseline, 6 months, 12 months
Title
Dominant quad isometric strength using a strain gauge
Time Frame
Baseline, 6 months, 12 months
Title
Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only)
Time Frame
Baseline, 6 months, 12 months
Title
Regional brain volumes using structural MRI
Time Frame
Baseline and 12 months
Title
Selected Pro- and anti-inflammatory cytokines in blood (subset only)
Description
IFN-alpha, IL-1 alpha, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-17, TNF-alpha, Rantes, CXCL1, IL-18, TGF-B
Time Frame
Baseline, 6 months, and 12 months
Title
Telomere Length
Time Frame
Baseline, 6 months, and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI -- the presence of both cognitive impairment and small vessel ischaemic disease. Specifically, individuals must meet the following inclusion criteria: Montreal Cognitive Assessment (MoCA) score less than 26 at screening; MMSE score of = or > 20 at screening; Community-dwelling; Lives in Metro Vancouver; Able to comply with scheduled visits, treatment plan, and other trial procedures; Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity; Stable on a fixed dose of cognitive medications (e.g., donepezil, galantamine, rivastigmine, memantine, etc.) that is not expected to change during the 12-month study period, or, if they are not on any of these medications, they are not expected to start them during the 12-month study period; Provide a personally signed and dated informed consent document indicating that the individual (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. In addition, an assent form will be provided at baseline and again at regular intervals; Able to walk independently; and Must be in sufficient health to participate in study's aerobic-based exercise training program. This will be based on medical history, vital signs, physical examination by study physicians, and written recommendation by family physician indicating individual's appropriateness to participate in an aerobic-based exercise training program. Exclusion Criteria: Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or MRI; Diagnosed with another type of dementia (e.g., AD) or other neurological conditions (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and mobility; Diagnosed previously with a genetic cause of SIVCI (e.g., CADASIL); At high risk for cardiac complications during exercise and/or unable to self-regulate activity or to understand recommended activity level (i.e., Class C of the American Heart Risk Stratification Criteria); Participating in regular RT in the last six months; Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility; Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid, etc.); or Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study. Unable to meet the specific scanning requirements of the UBC 3T MRI Research Centre. Specifically, we will exclude anyone with: pacemaker, brain aneurysm clip, cochlear implant, recent surgery or tattoos within the past 6 weeks, electrical stimulator for nerves or bones, implanted infusion pump, history of any eye injury involving metal fragments, artificial heart valve, orthopedic hardware, other metallic prostheses, coil, catheter or filter in any blood vessel, ear or eye implant, bullets, or other metallic fragments.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teresa Liu-Ambrose, PhD, PT
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Best, PhD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jennifer Davis, PhD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Charlie Goldsmith, PhD
Organizational Affiliation
Simon Fraser University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ging-Yuek Robin Hsiung, MD, PhD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roger Tam, PhD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thalia Field, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kenneth Madden, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33736706
Citation
Liu-Ambrose T, Dao E, Crockett RA, Barha CK, Falck RS, Best JR, Hsiung GR, Field TS, Madden KM, Alkeridy WA, Boa Sorte Silva NC, Davis JC, Ten Brinke LF, Doherty S, Tam RC. Reshaping the path of vascular cognitive impairment with resistance training: a study protocol for a randomized controlled trial. Trials. 2021 Mar 18;22(1):217. doi: 10.1186/s13063-021-05156-1.
Results Reference
derived

Learn more about this trial

Reshaping the Path of Vascular Cognitive Impairment (VCI)

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