Clinical trial NCT03790657: CONTROL Walking Study
Official title: Cerebral Networks of Locomotor Learning and Retention in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Aging
Keywords: aging
walking
brain
electrical stimulation
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2018-12-31
Enrollment: 100
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will randomized to one of two dosages of transcranial direct current stimulation (tDCS): Dosage A or Dosage B
Primary purpose: BASIC_SCIENCE

Brief summary: Older adults often experience substantial deficits in walking ability, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to changes in the brain that make performance of physical and cognitive tasks more difficult. Rehabilitation can help to improve walking ability, but effective rehabilitation is time consuming and expensive. New approaches are needed to improve the efficiency of rehabilitation so that gains in walking ability are widely attainable. A promising strategy is to focus on enhancing motor learning, which is defined as improved ability to perform a motor task due to practice or experience. The investigators will investigate the use of non-invasive brain stimulation to increase motor learning and retention of the newly learned walking skills. The investigators will also use neuroimaging to assess brain characteristics that explain how motor learning works. The knowledge gained from this study is expected to contribute to better understanding of mechanistic targets and intervention approaches to improve rehabilitation of walking.

Detailed description: Aging often leads to substantial declines in walking function, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to a lack of continued practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery of lost walking function in older adults, but major and persistent improvements are elusive. A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the ability to perform a motor task due to practice or experience. Unfortunately, in most clinical settings, the time and cost demands of delivering a sufficiently intensive motor learning intervention is not feasible. There is a need for research to develop strategies for enhancing motor learning of walking ("locomotor learning") in order to improve the effectiveness of neurorehabilitation.

The objective of this study is to use non-invasive brain stimulation to augment locomotor learning and to investigate brain networks that are responsible for locomotor learning in mobility-compromised older adults. The investigators have shown that frontal brain regions, particularly prefrontal cortex, are crucial to control of complex walking tasks. The investigators' neuroimaging and neuromodulation studies also show that prefrontal cortex structure and network connectivity are important for acquisition and consolidation of new motor skills. However, a major gap exists regarding learning of walking tasks. The proposed study is designed to address this gap. The investigators' pilot data from older adults shows that prefrontal transcranial direct current stimulation (tDCS) administered during learning of a complex obstacle walking task contributes to multi-day retention of task performance. In the proposed study the investigators will build upon this pilot work by conducting a full scale trial that also investigates mechanisms related to brain structure, functional activity, and network connectivity. The investigators will address the following specific aims:

Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task practice for retention of performance on a complex obstacle walking task.

Specific Aim 2: Determine the extent to which retention of performance is associated with individual differences in baseline and practice-induced changes in brain measures (including gray matter volume and brain network segregation).

Specific Aim 3: Investigate the extent to which tDCS modifies resting state network segregation.

The investigators anticipate that prefrontal tDCS will augment retention of locomotor learning, and that the data will provide the first evidence of specific brain mechanisms responsible for locomotor learning/retention in older adults with mobility deficits. This new knowledge will provide a clinically feasible intervention approach as well as reveal mechanistic targets for future interventions to enhance locomotor learning and retention.

Eligibility criteria: Inclusion Criteria:

* age 65 years or older
* preferred 10m walking speed \< 1.1 m/s
* self-report of "some difficulty with walking tasks, such as becoming tired when walking a quarter mile, or when climbing two flights of stairs, or when performing household chores."
* Willingness to be randomized to either study group and to participate in all aspects of study assessment and intervention

Exclusion Criteria:

* Diagnosed neurological disorder or injury of the central nervous system, or observation of symptoms consistent with such a condition (Alzheimer's, Parkinson's, stroke, etc.)
* Contraindications to non-invasive brain stimulation (e.g., metal in head, wound on scalp)
* Contraindications to magnetic resonance imaging (e.g., metal in body, claustrophobia, etc).
* Use of medications affecting the central nervous system
* severe arthritis, such as awaiting joint replacement
* severe obesity (body mass index \> 35)
* current cardiovascular, lung or renal disease; diabetes; terminal illness
* myocardial infarction or major heart surgery in the previous year
* cancer treatment in the past year, except for nonmelanoma skin cancers and cancers having an excellent prognosis (e.g., early stage breast or prostate cancer)
* current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder
* uncontrolled hypertension at rest (systolic \> 180 mmHg and/or diastolic \> 100 mmHg)
* bone fracture or joint replacement in the previous six months
* current participation in physical therapy for lower extremity function or cardiopulmonary rehabilitation
* current enrollment in any clinical trial
* difficulty communicating with study personnel, and/or non-English speaking
* planning to relocate out of the area during the study period
* clinical judgment of investigative team regarding safety or non-compliance

Primary outcomes:
measure: Walking speed change from baseline
timeFrame: Measured at follow up visit (approximately three weeks after baseline)
Secondary outcomes:
measure: Prefrontal cortex gray matter volume change from baseline
timeFrame: Measured at follow up visit (approximately three weeks after baseline)
measure: Brain resting state network segregation
timeFrame: Measured at follow up visit (approximately three weeks after baseline)
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
Study officials:
affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL
name: David J. Clark, DSc
role: PRINCIPAL_INVESTIGATOR
References: