Clinical trial NCT04029623: Partnered Rhythmic Rehabilitation in Prodromal Alzheimer's Disease
Official title: Partnered Rhythmic Rehabilitation for Enhanced Motor-Cognition in Prodromal Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prodromal Alzheimer's Disease
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-07-23
Enrollment: 66
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Interventions that affect many different aspects of human ability rather than just one aspect of human health are more likely to be successful in preventing and treating Alzheimer's disease (AD). Functional decline in AD is severely impacted by impaired ability to do physical actions while having to make decisions and concentrating, something scientists call motor-cognitive integration. Combined motor and cognitive training has been recommended for people with early AD, thus this study will use partnered, rhythmic rehabilitation (PRR), as an intervention to simultaneously target cardiovascular, social and motor-cognitive domains important to AD. PRR is moderate intensity, cognitively-engaging social dance that targets postural control systems, involves learning multiple, varied stepping and rhythmic patterns, and fosters tactile communication of motor goals between partners, enhancing social interaction's effect on cognition. Previous research demonstrates that PRR classes are safe and result in no injurious falls.

This study is a 12-month long Phase II single- blind randomized clinical trial using PRR in 66 patients with early AD. Participants with early AD will be randomly assigned to participate in PRR or a walking program for three months of biweekly sessions, followed by nine months of weekly sessions of PRR or walking. The overarching hypothesis is that PRR is safe, tolerable and associated with improved motor-cognitive function, and brain (neuronal), vascular (blood vessels) and inflammatory biomarkers that might affect function.

Detailed description: For people with early Alzheimer's disease (AD), treatment options to prevent declined function are extremely limited, because AD affects many areas of function. In early AD, people may have trouble physically doing things while also thinking, which is necessary for many activities in daily life. This problem might be helped by doing activities that challenge the mind and the body at the same time. Partnered rhythmic rehabilitation (PRR), which targets fitness, cognition, mobility and social engagement and may prevent future functional problems in AD.

This is a phase II single-blind randomized clinical trial to assess the safety, tolerability, and efficacy of PRR in individuals in the early stages of AD, also called prodromal AD (pAD) . Participants will be randomly assigned to 90-minute PRR or WALK classes. Both interventions will receive equal contact and monitoring from study staff. Participants will have two phases of intervention. In the three-month Training phase, participants will be assigned to 20, biweekly (90-minute) lessons over 12 weeks. In the nine-month Maintenance phase, participants will attend weekly lessons at least 3 times per month. Participants will undergo either PRR or Walking Exercise (WALK) interventions for one year, which will use de-escalating doses: two times per week for three months (Training) and weekly for nine months (Maintenance).

The first study aim is to determine acceptability, safety, tolerability and satisfaction with PRR in pAD. The second aim is to determine a) efficacy of PRR vs. WALK for improving motor-cognitive integration in pAD; b) to identify sensitive endpoints to power a future phase III trial. The researchers will also explore potential mechanisms by which PRR affects pAD. These mechanisms include functional brain measures, vascular, and inflammation measures (arterial stiffness; cerebral perfusion, task functional magnetic resonance imaging \[fMRI\]; inflammatory markers: cytokines and chemokines, endothelial adhesion markers.

Eligibility criteria: Inclusion Criteria:

* Amnestic mild cognitive impairment (MCI) will be defined using the AD Neuroimaging Initiative (ADNI) criteria (http://www.adni-info.org/Scientists/ADNIStudyProcedures.aspx). All MCI participants in ADNI are required to have an amnestic subtype defined as:

  * Subjective memory concern or a memory problem noted by their partner
  * Abnormal memory function documented by a specified education adjusted cutoff score on the delayed paragraph recall of the Anna Thompson story of the Logical Memory subtest from the Wechsler Memory Scale-Revised
  * Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive). Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI
  * Single or multi-domain amnestic MCI (both subtypes are at high risk for progression to AD)
  * Clinical Dementia Rating (CDR) = 0.5 (Memory Box score must be at least 0.5)
  * General functional performance sufficiently preserved
* Ability to walk 10 or more feet without an assistive device
* Completed six grades of education or has a good work history (sufficient to exclude intellectual disabilities)
* Achieves less than 150 minutes of moderate intensity or 75 minutes of vigorous intensity aerobic activity per week, which is the recommended amount of weekly exercise as per the US Department of Health and Human Services. Not involved in any structured exercise program within the past 3 months (brisk walks are considered formal exercise but leisurely walks are not)
* Not hospitalized within the last 60 days
* Willing to commit to a one year research program

Exclusion Criteria:

* Acute medical illness requiring hospitalization
* Uncontrolled congestive heart failure
* History of stroke in the past three years
* Inability to perform study procedures
* Inability to perform MRI (e.g. metal implants or cardiac pacemaker, claustrophobia)
* Medical or physical conditions that would preclude participation (e.g., severe arthritis or mobility problems, uncontrolled hypertension or diabetes, renal failure, history of angina with activity)
* On medications that could adversely affect cognition, eg: antipsychotics, opioids, stimulants, chemotherapy, anti-parkinsonian drugs (eg Levodopa), neurologic prescriptions to treat Multiple sclerosis and/or Parkinson's. Patients will also be excluded if they are not on stable doses of Aricept, or anticholinesterase inhibitors, eg Namenda, for at least 3 months
* Psychotic disorders
* Confounding neurologic conditions (e.g., active central nervous system (CNS) opportunistic infections, seizure disorders, head injury with loss of consciousness \>30 minutes, intracranial neoplasms, stroke with neurological or neuropsychiatric sequelae)
* Substance Use Disorder, Major Depressive and Generalized Anxiety Disorders within six months of evaluation

Primary outcomes:
measure: Change in Four Square Step Test (FSST) Time
timeFrame: Baseline, 3 months, 12 months
measure: Change in Acceptability
timeFrame: Baseline, Month 12
measure: Number of Injurious Falls
timeFrame: Month 12
measure: Attrition
timeFrame: Month 12
Secondary outcomes:
measure: Change in Timed Up and Go (TUG) Test - Cognitive Time
timeFrame: Baseline, 3 months, 12 months
measure: Change in Body Position Spatial Task (BPST)
timeFrame: Baseline, 3 months, 12 months
measure: Change in Lawton Instrumental Activities of Daily Living (IADL) Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Composite Physical Function (CPF) Scale Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Short Physical Performance Battery (SPPB) Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Mini-Balance Evaluation Systems Test (Mini-BESTest) Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in 6 Minute Walk Test (6MWT) Distance
timeFrame: Baseline, 3 months, 12 months
measure: Change in Preferred Gait Speed
timeFrame: Baseline, 3 months, 12 months
measure: Change in Backward Gait Speed
timeFrame: Baseline, 3 months, 12 months
measure: Change in Fast Gait Speed
timeFrame: Baseline, 3 months, 12 months
measure: Change in Clinical Dementia Rating (CDR) Questionnaire Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Flanker Task Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Set Shifting Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Spatial 1-Back Test Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Dot Counting Test Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Verbal Fluency Test Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Reverse Corsi Blocks Levels Completed
timeFrame: Baseline, 3 months, 12 months
measure: Change in Patient Health Questionnaire (PHQ-9) Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Multidimensional Scale of Perceived Social Support (MSPSS) Score
timeFrame: Baseline, 3 months, 12 months
measure: Change in Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline, 3 months, 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Madeleine Hackney, PhD
role: PRINCIPAL_INVESTIGATOR
References: