PROMOTE: Promotion of the Mind Through Exercise

• ClinicalTrials.gov Identifier: NCT01027858
• Recruitment Status: Completed
• First Posted: December 9, 2009
• Last Update Posted: October 4, 2017
• Sponsor: University of British Columbia
• Collaborators: Canadian Stroke Network; Heart and Stroke Foundation of Canada
• Information provided by (Responsible Party): Teresa Liu-Ambrose, University of British Columbia

Study Description

Brief Summary:

The investigators will conduct a proof-of-concept study to provide preliminary evidence of efficacy of aerobic-based exercise training for maintaining cognitive function, executive function, and everyday function in adults with mild vascular cognitive impairment.

Condition or disease	Intervention/treatment	Phase
Vascular Cognitive Impairment	Behavioral: Aerobic-based exercise training; Behavioral: CON (control; usual care)	Not Applicable

Detailed Description:

A total of 70 adults diagnosed with Ischaemic Vascular Cognitive Impairment (SIVCI) will be randomized to either a 6 month thrice weekly walking program or usual care. After 6 months of intervention, they will be followed for an additional 6 months. There will be three measurement sessions: baseline, 6 months (end of intervention period); and 12 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Role of Exercise on Cognition and Function in Seniors With Vascular Cognitive Impairment: A Randomized Controlled Trial
• Study Start Date: December 2009
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; AT (aerobic-based exercise training)	Behavioral: Aerobic-based exercise training; Six months of thrice-weekly walking 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).
Active Comparator: 2; CON (control; usual care)	Behavioral: CON (control; usual care); Nutrition education and usual care as prescribed by neurologist

Outcome Measures

Primary Outcome Measures :

1. This is a proof-of-concept study. The primary endpoints are: ADAS-Cog [ Time Frame: baseline, 6 months, and 12 months ]
2. EXIT-25 [ Time Frame: baseline, 6 months, and 12 months ]
3. ADCS-ADL [ Time Frame: baseline, 6 months, and 12 months ]

Secondary Outcome Measures :

1. Secondary outcomes of interest include: performance of specific executive processes [ Time Frame: baseline, 6 months, and 12 months ]
2. Physical function [ Time Frame: baseline, 6 months, and 12 months ]
3. Inflammatory biomarkers [ Time Frame: baseline, 6 months, and 12 months ]
4. Serum glucose and lipids. These will be assessed at 6 and 12 months. [ Time Frame: baseline, 6 months, and 12 months ]

Other Outcome Measures:

1. Brain Structure [ Time Frame: Baseline and 6 months ]
   Volume and white matter lesions.
2. Brain Function [ Time Frame: Baseline and 6 months ]
   fMRI and resting state

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI as outlined by Erkinjuntti and colleagues (1), which requires the presence of both cognitive syndrome (as defined in Section A below) and small vessel ischaemic disease (as defined in Section B below).

A. Cognitive Syndrome defined as:

1. Dysexecutive Syndrome: Some impairment in goal formulation, initiation, planning, organizing, sequencing, executing, set-shifting and maintenance, or abstracting.
2. Memory Deficit: Some impairment in recall, relative intact recognition, less severe forgetting, benefit from cues.
3. Progression: Deterioration of A1 and A2 from a previous higher level of functioning that are not per se interfering with complex occupational and social activities.

B. Small Vessel Ischaemic Disease defined as:

1. Evidence of relevant cerebrovascular disease by brain imaging (in the last 12 months) defined as the presence of both:

   i. Periventricular and deep white matter lesions: Patchy areas of low attenuation (intermediate density between that of normal white matter and that of intraventricular cerebro-spinal fluid) or diffuse symmetrical areas of low attenuation with ill defined margins extending to the centrum semiovale plus at least one lacunar infarct (correlating to the white matter grading scale greater than 3 from the Cardiovascular Health Study) (2,3); and ii. Absence of cortical and/or cortico-sub-cortical non-lacunar territorial infarcts and watershed infarcts, haemorrhages indicating large vessel disease, signs of normal pressure hydrocephalus, or other specific causes of white matter lesions (e.g., multiple sclerosis, leukodystrophies, sarcoidosis, brain irradiation, etc).

2. Presence or a history of neurological signs as evidence for cerebrovascular disease such as hemiparesis, lower facial weakness, Babinski sign, sensory deficit, dysarthria, gait disorder, extrapyramidal signs consistent with sub-cortical brain lesion(s).

In addition, individuals must meet the following inclusion criteria:

1. Montreal Cognitive Assessment (MoCA) (4) score less than 26 at screening;
2. MMSE (5) score of > 20 at screening;
3. Community-dwelling;
4. Lives in Metro Vancouver;
5. Have a caregiver, family member, or friend who interacts with him/her on a weekly basis;
6. Able to comply with scheduled visits, treatment plan, and other trial procedures;
7. Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity;
8. 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;
9. 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;
10. Able to walk independently; and
11. 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. 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);
4. Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility;
5. 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
6. Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study.

Contacts and Locations

Locations

Canada, British Columbia

University of British Columbia

Vancouver, British Columbia, Canada

Sponsors and Collaborators

University of British Columbia

Canadian Stroke Network

Heart and Stroke Foundation of Canada

Investigators

• Principal Investigator: Teresa Liu-Ambrose, Ph.D, PT; University of British Columbia
• Study Director: Janice Eng, Ph.D; University of British Columbia
• Study Director: Lara Boyd, Ph.D; University of British Columbia
• Study Director: Robin Hsiung, Ph.D; University of British Columbia
• Study Director: Claudia Jacova, Ph.D; University of British Columbia
• Study Director: Howard Feldman, MD; University of British Columbia
• Study Director: Penny Brasher, Ph.D; University of British Columbia
• Study Director: Philip Lee, Ph.D; University of British Columbia

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Barha CK, Hsiung GYR, Liu-Ambrose T. The Role of S100B in Aerobic Training Efficacy in Older Adults with Mild Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial. Neuroscience. 2019 Jul 1;410:176-182. doi: 10.1016/j.neuroscience.2019.04.052. Epub 2019 May 7.

Dao E, Best JR, Hsiung GR, Sossi V, Jacova C, Tam R, Liu-Ambrose T. Associations between cerebral amyloid and changes in cognitive function and falls risk in subcortical ischemic vascular cognitive impairment. BMC Geriatr. 2017 Jun 28;17(1):133. doi: 10.1186/s12877-017-0522-4.

Davis JC, Hsiung GR, Bryan S, Best JR, Eng JJ, Munkacsy M, Cheung W, Chiu B, Jacova C, Lee P, Liu-Ambrose T. Economic evaluation of aerobic exercise training in older adults with vascular cognitive impairment: PROMoTE trial. BMJ Open. 2017 Mar 29;7(3):e014387. doi: 10.1136/bmjopen-2016-014387.

Liu-Ambrose T, Best JR, Davis JC, Eng JJ, Lee PE, Jacova C, Boyd LA, Brasher PM, Munkacsy M, Cheung W, Hsiung GR. Aerobic exercise and vascular cognitive impairment: A randomized controlled trial. Neurology. 2016 Nov 15;87(20):2082-2090. Epub 2016 Oct 19.

Davis JC, Hsiung GY, Bryan S, Jacova C, Jacova P, Munkacsy M, Cheung W, Lee P, Liu-Ambrose T. Agreement between Patient and Proxy Assessments of Quality of Life among Older Adults with Vascular Cognitive Impairment Using the EQ-5D-3L and ICECAP-O. PLoS One. 2016 Apr 21;11(4):e0153878. doi: 10.1371/journal.pone.0153878. eCollection 2016.

Dao E, Hsiung GY, Sossi V, Jacova C, Tam R, Dinelle K, Best JR, Liu-Ambrose T. Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment. BMC Neurol. 2015 Oct 12;15:197. doi: 10.1186/s12883-015-0459-1. Erratum in: BMC Neurol. 2016;16(1):157.

Liu-Ambrose T, Eng JJ, Boyd LA, Jacova C, Davis JC, Bryan S, Lee P, Brasher P, Hsiung GY. Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment. BMC Neurol. 2010 Feb 17;10:14. doi: 10.1186/1471-2377-10-14.

• Responsible Party: Teresa Liu-Ambrose, Principal Investigator, University of British Columbia
• ClinicalTrials.gov Identifier: NCT01027858
• Other Study ID Numbers: H09-00529
• First Posted: December 9, 2009
• Last Update Posted: October 4, 2017
• Last Verified: October 2017

Keywords provided by Teresa Liu-Ambrose, University of British Columbia:

exercise; aerobic exercise training; vascular cognitive impairment; Mild Sub-cortical Ischaemic Vascular Cognitive Impairment (SIVCI)

Additional relevant MeSH terms:

Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders