Reshaping the Path of Vascular Cognitive Impairment (VCI)

Transient Ischemic Attack Clinical Trial

Official title:

Reshaping the Path of Vascular Cognitive Impairment With Resistance Training

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02669394
• Other study ID #: H15-00972
• Status: Completed
• Phase: N/A
• Start date: May 17, 2016
• Est. completion date: June 2, 2022

Study information

• Verified date: January 2024
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: June 2, 2022
• Est. primary completion date: June 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Dementia, Vascular
• Ischemic Attack, Transient
• Subcortical Vascular Dementia
• Transient Ischemic Attack
• Vascular Cognitive Impairment

Intervention

Behavioral:
• Resistance exercise training
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).
• Control: stretching and relaxation program
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.

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)	ADAS-Cog 13 Plus additional cognitive tests	Baseline, 6 months, and 12 months
Primary	Change in white matter health as measured by total white matter lesion volume	White matter hyperintensity volume in mm3	Baseline to 12 months
Secondary	Executive functions as measured by standard neuropsychological tests		Baseline, 6 months, and 12 months
Secondary	Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV) (subset only)		Baseline and 12 months
Secondary	Cardiometabolic risk factors as measured by blood panel (subset only)		Baseline, 6 months, and 12 months
Secondary	Cardiometabolic risk factors as measured by body mass index		baseline, 6 months, and 12 months
Secondary	Cardiometabolic risk factors as measured by waist to hip ratio		baseline, 6 months, and 12 months
Secondary	Physiological falls risk as measured by the Physiological Profile Assessment		baseline, 6 months, and 12 months
Secondary	Mobility and balance as measured by the Short Physical Performance Battery		baseline, 6 months, and 12 months
Secondary	Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)		baseline, 6 months, and 12 months
Secondary	Quality of life as measured by the Medical Outcomes Study Short Form-6D (SF-6D)		baseline, 6 months, and 12 months
Secondary	White matter integrity as measured by diffusion tensor imaging		baseline and 12 months
Secondary	Myelin plasticity as measured by multicomponent relaxation imaging		baseline and 12 months
Secondary	Memory as measured by standard neuropsychological tests		baseline, 6 months, and 12 months
Secondary	Upper body strength as measured by grip strength		baseline, 6 months, and 12 months
Secondary	Lower body strength as measured by 30 sec sit to stand test		baseline, 6 months, and 12 months
Secondary	Functional capacity as measured by 6 minute walk test		Baseline, 6 months, 12 months
Secondary	Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only)		Baseline, 6 months, 12 months
Secondary	Self-reported physical activity as measured by the PASE questionnaire		Monthly
Secondary	NIH Cognitive Toolbox		Baseline, 6 months, 12 months
Secondary	Isokinetic strength of the lower limb (subset only)		Baseline, 6 months, 12 months
Secondary	Functional connectivity using resting state fMRI (subset only)		Baseline and 12 months
Secondary	Health resource utilization		Baseline and every 3 months
Secondary	Prospective falls via monthly falls calendars		Monthly
Secondary	Mobility using Timed up and Go Test		Baseline, 6 months, 12 months
Secondary	Dual-task ability using dual-task timed up and go test		Baseline, 6 months, 12 months
Secondary	Dual task gait using Gaitrite mat (subset only)		Baseline, 6 months, 12 months
Secondary	Cognitive function using ADAS-Cog 13		Baseline, 6 months, 12 months
Secondary	Dominant quad isometric strength using a strain gauge		Baseline, 6 months, 12 months
Secondary	Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only)		Baseline, 6 months, 12 months
Secondary	Regional brain volumes using structural MRI		Baseline and 12 months
Secondary	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	Baseline, 6 months, and 12 months
Secondary	Telomere Length (subset only)		Baseline, 6 months, and 12 months
Secondary	Sleep quality as measured by MW8		Baseline, 6 months, and 12 months