Clinical trial NCT02669394: Reshaping the Path of Vascular Cognitive Impairment (VCI)
Official title: Reshaping the Path of Vascular Cognitive Impairment With Resistance Training
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transient Ischemic Attack
Vascular Cognitive Impairment
Subcortical Vascular Dementia
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2016-02-01
Enrollment: 91
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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:

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.

Primary outcomes:
measure: Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)
timeFrame: Baseline, 6 months, and 12 months
measure: Change in white matter health as measured by total white matter lesion volume
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Executive functions as measured by standard neuropsychological tests
timeFrame: Baseline, 6 months, and 12 months
measure: Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV) (subset only)
timeFrame: Baseline and 12 months
measure: Cardiometabolic risk factors as measured by blood panel (subset only)
timeFrame: Baseline, 6 months, and 12 months
measure: Cardiometabolic risk factors as measured by body mass index
timeFrame: baseline, 6 months, and 12 months
measure: Cardiometabolic risk factors as measured by waist to hip ratio
timeFrame: baseline, 6 months, and 12 months
measure: Physiological falls risk as measured by the Physiological Profile Assessment
timeFrame: baseline, 6 months, and 12 months
measure: Mobility and balance as measured by the Short Physical Performance Battery
timeFrame: baseline, 6 months, and 12 months
measure: Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
timeFrame: baseline, 6 months, and 12 months
measure: Quality of life as measured by the Medical Outcomes Study Short Form-6D (SF-6D)
timeFrame: baseline, 6 months, and 12 months
measure: White matter integrity as measured by diffusion tensor imaging
timeFrame: baseline and 12 months
measure: Myelin plasticity as measured by multicomponent relaxation imaging
timeFrame: baseline and 12 months
measure: Memory as measured by standard neuropsychological tests
timeFrame: baseline, 6 months, and 12 months
measure: Upper body strength as measured by grip strength
timeFrame: baseline, 6 months, and 12 months
measure: Lower body strength as measured by 30 sec sit to stand test
timeFrame: baseline, 6 months, and 12 months
measure: Functional capacity as measured by 6 minute walk test
timeFrame: Baseline, 6 months, 12 months
measure: Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only)
timeFrame: Baseline, 6 months, 12 months
measure: Self-reported physical activity as measured by the PASE questionnaire
timeFrame: Monthly
measure: NIH Cognitive Toolbox
timeFrame: Baseline, 6 months, 12 months
measure: Isokinetic strength of the lower limb (subset only)
timeFrame: Baseline, 6 months, 12 months
measure: Functional connectivity using resting state fMRI (subset only)
timeFrame: Baseline and 12 months
measure: Health resource utilization
timeFrame: Baseline and every 3 months
measure: Prospective falls via monthly falls calendars
timeFrame: Monthly
measure: Mobility using Timed up and Go Test
timeFrame: Baseline, 6 months, 12 months
measure: Dual-task ability using dual-task timed up and go test
timeFrame: Baseline, 6 months, 12 months
measure: Dual task gait using Gaitrite mat (subset only)
timeFrame: Baseline, 6 months, 12 months
measure: Cognitive function using ADAS-Cog 13
timeFrame: Baseline, 6 months, 12 months
measure: Dominant quad isometric strength using a strain gauge
timeFrame: Baseline, 6 months, 12 months
measure: Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only)
timeFrame: Baseline, 6 months, 12 months
measure: Regional brain volumes using structural MRI
timeFrame: Baseline and 12 months
measure: Selected Pro- and anti-inflammatory cytokines in blood (subset only)
timeFrame: Baseline, 6 months, and 12 months
measure: Telomere Length (subset only)
timeFrame: Baseline, 6 months, and 12 months
measure: Sleep quality as measured by MW8
timeFrame: Baseline, 6 months, and 12 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Teresa Liu-Ambrose, PhD, PT
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: John Best, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Jennifer Davis, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Simon Fraser University
name: Charlie Goldsmith, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Ging-Yuek Robin Hsiung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Roger Tam, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Thalia Field, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Kenneth Madden, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.