mSIM: Mobile Simultaneous Aerobic Exercise and Memory Training Intervention for Amnestic Mild Cognitive Impairment

Study Overview
=================
Brief Summary
-----------------
The mSIM study involves developing and conducting feasibility testing of a web-based application that will deliver mobile-based simultaneous exercise and memory skills training program (mSIM) for amnesic Mild Cognitive Impairment (aMCI) patients. The randomized control trial (RCT) will evaluate the efficacy of mSIM on memory performance and everyday functioning using 2 study arms (Group 1 activity monitoring control (via Fitbit) (CON) vs Group 2 mSIM intervention plus activity monitoring via Fitbit). mSIM treatment response will be evaluated using neuropsychological and functional evaluation. Concentration levels of peripheral biomarkers Brain-derived neurotrophic factor (BDNF) and norepinephrine (NE) also be assessed.

Detailed Description
-----------------
The purpose of the study is to create a web-based cognitive compensatory, and predominately memory skills, training course that is delivered on a mobile device and compatible with use on a stationary bicycle and test its efficacy on memory and functional ability. Participants will be recruited from (1) the Pacific Brain Health Center in Santa Monica, which is a high-volume memory-care and dementia outpatient clinic within a large physician medical group affiliated with Providence Saint John's Health Center, (2) advertisement to participants in the local community, and (3) establishment of a website landing page that permits interested individuals to contact the trial coordinator. Up to five participants will be course beta testers. They will receive a truncated version of the course and will provide detailed feedback. 30 participants will be randomized into one of two groups. Group 1 (control arm) will have their physical activity levels continuously monitored (via Fitbit). Participants will receive the Experimental Research Subject's Bill of Rights prior to signing the informed consent form (ICF), authorization of use and disclosure of protected health information (PHI), and authorization of medical record release for the subject's treating physician, will be obtained from each participant prior to enrolling in the study. A copy of all signed ICF's will be given to the participants, and the investigator will retain the original. Group 2 (active arm) will receive the mSIM intervention plus activity monitoring (via Fitbit). Group 2 will first undergo 2-6 week of an exercise ramp-up (2x/week) until they can sustain 40 minutes at 50% heart rate reserve (HRR). The intensity for mSIM training will be 40-60% HRR. After the ramp-up phase the mSIM participants will begin the 12-week intervention, comprised of 2 60-minute sessions/week. mSIM treatment response will be evaluated using neuropsychological and functional evaluation. Assessments will occur at baseline, mid-trial (3-4 months) and post-trial (5-6 months). Concentration levels of peripheral biomarkers BDNF and NE at baseline and post-trial (5-6 months) will also be assessed.

Official Title
-----------------
Mobile Technology-Based Simultaneous Aerobic Exercise and Memory Training Intervention for Older Adults With Mild Cognitive Impairment

Conditions
-----------------
Amnestic Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Behavioral: mSIM intervention plus activity monitoring
* Behavioral: Activity monitoring


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Subjects must be age 50 to 80 at time of informed consent. Subjects must confirm an aMCI diagnosis either by providing records from a clinical assessment within 6 months of enrollment in this study or through a brief memory assessment by study staff at screening. Subjects must be proficient in spoken and written English for consenting as well as for study participation since the intervention in this study is currently only available in English. Subjects with medical conditions must be stable for these conditions. Stable control on medication is acceptable. Subjects, with or without assistance, must be able to use a computer and web interface. If assistance is needed, it must be readily available to them. Subjects are required to have internet with Wi-Fi at the location of their mSIM training. Subject must have normal visual acuity (or corrected to normal) and normal color vision as indicated by self-report. Subject must have adequate hearing acuity as indicated by self-report. Subject must have adequate motor capacity to use a mobile phone/iPad/computer as indicated by self-report. Subjects must be able to provide medical clearance to participate in an unsupervised, moderate intensity exercise program from a physician. Exclusion Criteria Subjects must not have an existing diagnosis of a neurodegenerative disorder (e.g., Alzheimer's Disease, Lewy Body Dementia, Frontal-Temporal Dementia). Subjects must not have a prior diagnosis that might impact cognition and movement abilities including: significant cardiovascular disease, significant respiratory disease, illness or injury, substance abuse, schizophrenia, bipolar disorder, or other neurological diseases. Subjects must not have a previous Mini Mental State Exam (MMSE) score below 19. Subjects must not have a previous Clinical Dementia Rating (CDR) global score of ≥2. Subjects must not have a Montreal Cognitive Assessment (MoCA)43 score of below 18 previously or during their screening evaluation. Subjects must not demonstrate a progression of aMCI to dementia at screening based on the best judgement of a study Clinical Neuropsychologist. Subjects must not currently participate in a high level of physical activity prior to study start as assessed by the International Physical Activity Questionnaire (IPAQ) at screening. Subjects must not endorse that they are unable to participate in moderate intensity aerobic activities, such as fast walking or passing/kicking a ball to a partner at screening.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will include two arms: Arm 1: activity monitoring only control (CON), Arm 2: active intervention with mSIM program (mSIM) plus activity monitoring (via Fitbit), to evaluate the efficacy of the mSIM intervention on memory performance and everyday functioning. The 'Activity monitoring only' arm will serve as the control group. Study objectives include measuring treatment related changes in memory performance and everyday functioning along with putative biomarkers of the behavioral changes.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 (No treatment)<br>Group 1: Participants will have continuous activity monitoring (via Fitbit) | Behavioral: mSIM intervention plus activity monitoring<br>* Participants will receive the full mSIM intervention and be monitored (via Fitbit)<br>|
| Experimental: Group 2 (Experimental)<br>Group 2: Participants will receive the mSIM treatment and have their activity monitored continuously (via Fitbit) | Behavioral: Activity monitoring<br>* Participants will have activity monitored (via Fitbit)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory Function Composite Score | Global Z-Score including results from RAVLT (Rey's Auditory Verbal Learning Test), Wechsler Memory Scale Fourth Edition (WMS-IV) Logical Memory and Visual Reproduction tests. | Baseline, approximately 3 months and approximately 6 months | 
| Functional Abilities | Assessed using the Multifactorial Memory Questionnaire (MMQ) | Baseline, approximately 3 months and approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting brain-derived neurotrophic factor (BDNF) | Resting level of serum-derived BDNF | Baseline and approximately 6 months | 
| Resting norepinephrine (NE) | Resting level of plasma-derived norepinephrine (NE) | Baseline and approximately 6 months |