Clinical trial NCT03122236: Combining tDCS and Neurorehabilitation to Treat Age-related Deficits of Mobility and Cognition: UPfront Walking Study
Official title: Combining tDCS and Neurorehabilitation to Treat Age-related Deficits of Mobility and Cognition: UPfront Walking Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mobility Limitation
Cognitive Impairment
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2017-04-20
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Maximum age (years): 110
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will take part in a 6-week, 18-session neurorehabilitation led by qualified and trained study personnel. Participants will be randomized to one of three groups: 1) standard walking neurorehabilitation with sham tDCS ('standard/sham' group), 2) complex walking neurorehabilitation with sham tDCS ('complex/sham' group), or 3) complex walking neurorehabilitation with active anodal tDCS ('complex/active' group). Training logs will be maintained to gauge the content and intensity of training.
Primary purpose: TREATMENT

Brief summary: Loss of mobility and cognitive ability are serious conditions that threaten the independence of older adults. The objective of this study is to initiate a line of research to develop a novel therapeutic intervention to enhance both mobility and cognition via neuroplasticity of frontal/executive circuits.

Detailed description: Frontal lobe dysfunction has been implicated as a factor contributing to gait deficits in some individuals with Alzheimer's disease, frontotemporal dementia and vascular dementia. There is a critical gap in knowledge about what therapeutic strategies are effective for maintaining or reinstating function in this critical brain region in order to preserve physical and cognitive health in older adults. The goal of our research is to develop a novel therapeutic intervention to enhance both mobility and cognition via neuroplasticity of frontal/executive control circuits. The Investigator will engage neuroplasticity of frontal circuits in two ways. The first is through neurorehabilitation with "complex walking tasks" (CWTs), such as obstacle crossing, obstacle avoidance and walking on non-uniform surfaces. CWTs are a potent behavioral approach for engaging prefrontal circuits. Furthermore, CWTs are crucial to successful ambulation in the home and community settings and therefore provide an ecologically valid therapeutic approach. The second approach that the Investigator will use to engage neuroplasticity of frontal circuits is anodal transcranial direct current stimulation (tDCS). Anodal tDCS is a safe, non-invasive neuromodulation technique. It has previously been shown to induce excitatory effects on brain tissue and, in single-session assessments, to improve performance during complex walking tasks. tDCS has also been shown to be an effective adjuvant for enhancing the effects of cognitive training. The objective of this study is to calculate effect size, establish variance of response and demonstrate feasibility of the experimental interventions in order to plan for a full scale clinical trial. Participants will include thirty older adults who demonstrate evidence of frontal/executive impairment. Participants will be randomized to one of three groups: 1) standard walking neurorehabilitation with sham tDCS ('standard/sham' group), 2) complex walking neurorehabilitation with sham tDCS ('complex/sham' group), or 3) complex walking neurorehabilitation with active anodal tDCS ('complex/active' group). Functional near infrared spectroscopy (fNIRS) will be used to explore intervention-induced changes in prefrontal cortical activity. Assessments will be conducted at baseline, post-treatment and 3-month follow up. The Investigator propose the following specific aims:

Specific Aim 1: Determine preliminary efficacy for recovery of mobility and cognitive function.

Specific Aim 2: Demonstrate feasibility/safety of tDCS as an adjuvant to rehabilitation.

Specific Aim 3: Explore the relationship between prefrontal activity and behavioral outcomes The data collected here will provide the information needed to justify and plan a future full scale clinical trial to assess the relative efficacy and underlying mechanisms of each intervention approach.

Eligibility criteria: Inclusion criteria

* preferred 10m walking speed \< 1.0 m/s
* 40th-80th percentile rank (age and education corrected score) on NIH toolbox executive assessments: Card Sort Test and Flanker test
* willingness to be randomized to either intervention and to participate in all aspects of study assessment and intervention

Exclusion criteria

* contraindications to non-invasive brain stimulation and/or MRI including metal in the head, pacemaker, known abnormal cranial fissures/holes.
* difficulty communicating with study personnel
* uncontrolled hypertension at rest (systolic \> 180 mmHg and/or diastolic \> 100 mmHg)
* low vision that cannot be corrected by wearing glasses. Low visual will be operationally defined as visual acuity less than 20/70 on a standard eye chart, or difficulty performing complex walking tasks due to visual conditions affecting accurate navigation around and over obstacles (self-reported or observed by examiner).
* illiterate, due to the likelihood of difficulties performing some of the cognitive tasks
* non-English speaking, due to the likelihood of difficulties following instructions during therapy and during assessments
* use of medications that are know to modify tDCS effectiveness including those with anticholinergic, GABAergic, or glutamatergic properties, or sodium channel blockers
* clinical judgment of investigative team

Primary outcomes:
measure: Mobility: Figure-of-eight Walking Test (Figure-8 Walk Test)
timeFrame: Change (value at 6 weeks minus value at baseline)
Secondary outcomes:
measure: Cognitive Composite Executive Score on EXAMINER Battery
timeFrame: Change (value at 6 weeks minus value at baseline)
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: HealthStreet
state: Florida
city: Gainesville
country: United States
facility: UF Institute on Aging
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: David Clark, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chatterjee SA, Seidler RD, Skinner JW, Lysne PE, Sumonthee C, Wu SS, Cohen RA, Rose DK, Woods AJ, Clark DJ. Effects of Prefrontal Transcranial Direct Current Stimulation on Retention of Performance Gains on an Obstacle Negotiation Task in Older Adults. Neuromodulation. 2023 Jun;26(4):829-839. doi: 10.1016/j.neurom.2022.02.231. Epub 2022 Apr 8.