Combinatory Rehabilitation Used for Substantially Helping Individuals With Traumatic Brain Injury

NCT ID: NCT05716048

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-21
• Study Completion Date: 2028-02-28

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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

KF-mSMT Plus Aerobic Exercise Training

Participants will undergo 12 weeks of supervised aerobic cycling exercise training. During the last 8 weeks of cycling exercise, participants will also undergo treatment with the Kessler Foundation modified Story Memory Technique as an approach for cognitive rehabilitation.

Group Type: EXPERIMENTAL

KF-mSMT Plus Aerobic Exercise Training

Intervention Type: BEHAVIORAL

Participants 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

Participants will undergo 12 weeks of supervised stretching and toning exercise training. During the last 8 weeks of stretching exercise, participants will also undergo treatment with the Kessler Foundation modified Story Memory Technique as an approach for cognitive rehabilitation.

Group Type: ACTIVE_COMPARATOR

KF-mSMT Plus Stretching Exercise Training

Intervention Type: BEHAVIORAL

Participants 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

Interventions

KF-mSMT Plus Aerobic Exercise Training

Participants 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

Intervention Type: BEHAVIORAL

KF-mSMT Plus Stretching Exercise Training

Participants 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

Intervention Type: BEHAVIORAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kessler Foundation

OTHER

Sponsor Role: lead

Responsible Party

Brian Sandroff

Senior Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy D Chiaravalloti, PhD

Role: PRINCIPAL_INVESTIGATOR

Kessler Foundation

Locations

Kessler Foundation

West Orange, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nancy Moore, MA

Role: CONTACT

nbmoore@kesslerfoundation.org

973-324.8450

Facility Contacts

Brian M Sandroff, PhD

Role: primary

Other Identifiers

R-1195-22

Identifier Type: -

Identifier Source: org_study_id