About this trial
New learning and memory impairment (NLMI) is a common and devastating manifestation of TBI associated with substantial life burdens. Persons with moderate to severe TBI have shown improvement in NLM for prose material (e.g. story) as well as beneficial changes in default-mode network (DMN) activation during list-learning19 following treatment with the Kessler Foundation modified Story Memory Technique® (KF-mSMT®). Benefits, however, were moderate and did not yield downstream improvements in daily life. It is thus critical to examine other approaches to complement the KF-mSMT® for robustly managing NLMI in TBI. The proposed RCT will be the first to include aerobic exercise training (AET) as a highly-promising complement to the KF-mSMT® for robustly managing NLMI, examining impact on NLM, its neural correlates, and daily life in NLM impaired persons with moderate-to-severe TBI. We thus propose a two-arm, parallel group, double-blind RCT comparing the effects of the KF-mSMT+AET with the KF-mSMT+S/T (active control condition) on NLM (Aim 1), hippocampal MRI (Aim 2), and daily life outcomes (Aim 3). 60 NLM impaired persons with moderate-to-severe TBI will be randomized to one of 2 conditions (30 per condition). Each condition will take place 3 days per week for 12 weeks and will be supervised by KF personnel. Participants will be blinded as to the intent of the conditions. We will further explore baseline predictors of clinically meaningful changes in NLM for those completing the KF-mSMT + AET condition (Exploratory Aim 4). If successful, this trial will position combinatory KF-mSMT and AET within the clinician's arsenal for robustly managing NLMI in persons with TBI. By augmenting the effects of KF-mSMT with AET, this treatment aims to exert a powerful countermeasure to TBI-related NLMI, and ultimately help those with TBI-related NLMI return to the workforce, independently manage their everyday lives, and maintain optimal quality of life. Additionally, while rigorously designed to answer the scientific question of the relative benefit of AET with the KF-mSMT, the proposed study is will likely provide some level of benefit to all study participants.
If successful, this trial will provide Class I evidence of combined KF-mSMT and AET for rehabilitating NLMI in TBI, based on standards published for therapeutic trials by the American Academy of Neurology, thus positioning such an approach within the clinician's arsenal for robustly managing NLMI. By augmenting the effects of KF-mSMT with AET, we anticipate this treatment will ultimately help those with TBI-related NLMI return to the workforce, independently manage their everyday lives, and maintain optimal quality of life.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age between 18-65 to control for age related brain changes
Diagnosis of moderate-to-severe TBI based on TBIMS criteria at least one year prior to enrollment
Having no to low substance use / involvement (drug/alcohol) as documented via ASSIST
Being insufficiently physically active based on a Godin Leisure-Time Exercise Questionnaire Health Contribution Score of <14
Disqualifiers
Regularly taking steroids & benzodiazapines to control for medications effects
Having a history of neurological disorders beyond TBI
Having a history of severe mental illness (e.g., schizophrenia, bipolar, severe major depression)
Having metal in the body, claustrophobia, and other risk factors that would make MRI scanning unsafe.
Trial design
Parallel
Treatments tested in this trial
KF-mSMT Plus Aerobic Exercise Training
BehavioralParticipants will undergo this combinatory intervention 3 days per week for 12 weeks. The combined session duration will begin with 15 minutes and last up to 2 hours by the end of the 12th week
KF-mSMT Plus Stretching Exercise Training
BehavioralParticipants will undergo this combinatory intervention 3 days per week for 12 weeks. The combined session duration will begin with 15 minutes and last up to 2 hours by the end of the 12th week
Treatment groups
Trial outcomes
Primary outcomes
Change in California Verbal Learning Test-3 Performance
This is a test of new learning and memory
Secondary outcomes
Change in hippocampal volume
This involves a structural MRI scan wherein the volume of the bilateral hippocampi will be measured.
Change in hippocampal activation
This involves an fMRI list-learning task wherein activation of the hippocampus during encoding and recall will be measured
Change in hippocampal resting-state functional connectivity
This involves a resting-state fMRI paradigm wherein connectivity between the hippocampus and other brain regions that are important for learning and memory will be measured.
Change in Everyday Memory Simulations Performance
This multi-component test examines aspects of memory that are relevant to daily life.
Sponsors and contacts
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