Clinical trial NCT02320864: The Strong Brain Study
Official title: A Pilot Study to Evaluate the Role of Brain Integrity on Post-hospital Sarcopenia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Osteoarthritis
Sarcopenia
Keywords: muscle strength
muscle weakness
hospitalization
surgery
total knee replacement
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2014-12-19
Enrollment: 18
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will comprise two age-matched participant groups: 1.) 'Healthy' non-demented (n=20) patients undergoing elective total knee arthroplasty, and 2.) age, education, and disease matched (osteoarthritis knee pain; n=20) non-surgery peers. We expect to screen 60 potential participants to yield 40 participants who complete the protocol. All participants will be recruited with the assistance of the Orthopedic Surgery Department at UFHealth. The parallel control group will originate from the parent study physician. Only right-handers will participate in this experiment because left-handedness is associated with greater variability in white matter organization and cognitive functions.

Brief summary: To evaluate operational aspects of studying pre to post surgery/hospitalization changes in the integrity of a major white matter pathways and how these contribute to reductions in the ability to produce forceful muscle contractions.

Detailed description: Hospitalization is a strong and independent risk factor for Sarcopenia. Older adults who are hospitalized in the previous year experience greater losses of lean mass and muscle strength than their non-hospitalized peers. Most of the research has focused on understanding muscle atrophy as the cause of weakness. However, post-hospitalization muscle weakness is not solely due to muscle atrophy- it explains less than 10% of the variance. The investigators propose that the sequela of hospitalization (e.g. deconditioning, disease severity, etc.) reduces the integrity of brain motor pattern that is used to produce forceful muscle contractions. Evidence from the literature suggests that central nervous system impairments explain approximately 60% of the variance in the loss in muscle strength observed following hospitalization. However, while these findings have helped to move the field forward, the measures lack spatial resolution. Accordingly, there remains a major gap in understanding whether deterioration of specific brain motor tracts contribute to post-hospitalization induced sarcopenia. The investigators intend to conduct a prospective cohort study to examine the integrity of the cortical-spinal white matter tract in post-hospitalized older adults. However, the investigators lack some essential elements in which to conduct this future study. Therefore, this pilot study will refine the following: patient eligibility, feasibility of collecting outcomes in patients, variances for statistical power, influence of covariates, timeline, patient attrition rates, data analysis strategies and magnetic resonance imaging protocol for mapping the cortical-spinal tract. The investigators will accomplish these operational aims efficiently and cost-effectively by leveraging funding with a newly awarded R01 by Dr. Catherine Price, which seeks to identify pre-surgical neuroimaging biomarkers following total knee arthroplasty (TKA) (R01NR014181; IRB# 487-2012). Specifically, the investigators will add measures of sarcopenia (muscle strength, mass and gait) and assess the integrity of the cortico-spinal tract. Measures will be collected in 20 patients before and after hospitalization (prior to surgery, 3 months and 12 months post-surgery) and 20 controls who are matched in age and disease severity at similar time points. In summary, there are long-term impairments that result from hospitalization in older adults that are not explained by the illness alone. This pilot study will result in subsequent larger NIH funded studies because the research is distinct from all others being conducted on muscle function, aging and effects of hospitalization.

Eligibility criteria: Inclusion Criteria:

* Aged 60 years old or older with no upper limit at time of baseline assessment
* Right handed; restriction due to left-right hemisphere laterality and white matter pathways
* Able to understand and speak English
* Willing to give informed consent

Exclusion Criteria:

* Any conditions that pose health risk with physical exertion during a strength test as discovered on a medical history (e.g. heart failure, surgical complications etc.)
* Cancer requiring treatment in past 5 years (exception: non-melanoma skin cancer)
* Serious infectious diseases (e.g., self-reported HIV, sepsis)
* Myocardial infarction/ CVA within last six months
* Congestive heart failure (NY stage III or IV)
* Chronic hepatitis
* History of organ transplantation
* Seizure disorders
* History of head trauma resulting in intensive care
* Current diagnosis of alcoholism
* Drug dependence, or a history of major tranquilizer use
* History of major stroke(s)
* Exposure to toxins or neuroleptics
* History of encephalitis
* Neurological signs of upper motor neuron disease, cerebellar involvement, supranuclear palsy, or orthostatic hypertension that causes fainting
* Major Depression or Major Depressive Episode within three months prior to study
* Claustrophobia
* Non-medical bodily metal
* Pace-maker device
* Less than five years of formal education
* Inability to read or write
* Self-reported hearing or vision impairment that interferes with standardized test administration

Primary outcomes:
measure: muscle strength
timeFrame: Change in baseline, 3 months and 12 months
measure: Muscle mass
timeFrame: Change in baseline, 3 months and 12 months
Secondary outcomes:
measure: Short physical performance batter score (SPPB)
timeFrame: Change in baseline, 3 months and 12 months
measure: 6-minute walk distance
timeFrame: Change in baseline, 3 months and 12 months
measure: Spatiotemporal gait characteristics
timeFrame: Change in baseline, 3 months and 12 months
measure: Brain MRI derived corticospinal tract integrity from foot motor cortex to cerebral peduncle
timeFrame: Change in baseline, 3 months and 12 months
Other outcomes:
measure: perceived pain
timeFrame: Change in baseline, 3 months and 12 months
measure: physical activity
timeFrame: Change in baseline, 3 months and 12 months
Locations:
city: Gainesville
country: United States
facility: Institute on Aging
state: Florida
Study officials:
affiliation: University of Florida
name: Todd M Manini, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Adam J Woods, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: