Clinical trial NCT05716048: Combinatory Rehabilitation Used for Substantially Helping Individuals With Traumatic Brain Injury
Official title: Randomized Controlled Trial of Combined Cognitive Rehabilitation and Exercise Training for Learning and Memory in Persons With Moderate to Severe Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Traumatic Brain Injury
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: Inclusion Criteria:

* 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
* Having a proficiency in the English language
* Being right handed to control for brain organization
* Having chronic medical conditions (e.g. diabetes) in addition to TBI will require approval to participate from a physician, consistent with PAR-Q+.
* Having an in-tact ability to follow directions based on the Telephone Interview for Cognitive Status (TICS-M) (i.e., TICS-M scores of ≥18)
* Demonstrating new learning and memory impairment based on Open-Trial Selective Reminding Task (OT-SRT) scores at least 1.5 standard deviations below healthy controls (8+ trials to reach criterion)

Exclusion Criteria:

* 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.
* Having moderate or high risk for exercise training contraindications (e.g. diabetes), defined as ≥1 YES on pages 2-3 of the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+)
* Having significantly impaired vision by scotomas (corrected vision in worse eye worse than 20/60), diplopia, or nystagmus.

Primary outcomes:
measure: Change in California Verbal Learning Test-3 Performance
timeFrame: From 0 to 12 weeks
Secondary outcomes:
measure: Change in hippocampal volume
timeFrame: From 0 to 12 weeks
measure: Change in hippocampal activation
timeFrame: From 0 to 12 weeks
measure: Change in hippocampal resting-state functional connectivity
timeFrame: From 0 to 12 weeks
measure: Change in Everyday Memory Simulations Performance
timeFrame: From 0 to 12 weeks
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Foundation
state: New Jersey
Study officials:
affiliation: Kessler Foundation
name: Nancy D Chiaravalloti, PhD
role: PRINCIPAL_INVESTIGATOR
References: