Traumatic Brain InjuryPhase 1CRUSH-ITNCT05716048
Combinatory Rehabilitation Used for Substantially Helping Individuals With Traumatic Brain Injury
A Phase 1 study testing KF-mSMT Plus Aerobic Exercise Training and KF-mSMT Plus Stretching Exercise Training in people with Traumatic Brain Injury, run by Kessler Foundation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- KF-mSMT Plus Aerobic Exercise Training and KF-mSMT Plus Stretching Exercise Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2023to 28 Feb 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Kessler Foundation
West Orange, New Jersey, 07052
Brian M Sandroff, PhD
About this study
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
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
- Being tested
- KF-mSMT Plus Aerobic Exercise Training, KF-mSMT Plus Stretching Exercise Training
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KF-mSMT Plus Aerobic Exercise TrainingBehavioural
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 TrainingBehavioural
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
| Study group | Role | What they receive |
|---|---|---|
| KF-mSMT Plus Aerobic Exercise Training | Experimental | 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. Receives: Behavioral: KF-mSMT Plus Aerobic Exercise Training |
| KF-mSMT Plus Stretching Exercise Training | Active comparator | 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. Receives: Behavioral: KF-mSMT Plus Stretching Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in California Verbal Learning Test-3 Performance
This is a test of new learning and memory
Measured: From 0 to 12 weeks
Secondary outcomes (4)
Change in hippocampal volume
This involves a structural MRI scan wherein the volume of the bilateral hippocampi will be measured.
Measured: From 0 to 12 weeks
Change in hippocampal activation
This involves an fMRI list-learning task wherein activation of the hippocampus during encoding and recall will be measured
Measured: From 0 to 12 weeks
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.
Measured: From 0 to 12 weeks
Change in Everyday Memory Simulations Performance
This multi-component test examines aspects of memory that are relevant to daily life.
Measured: From 0 to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2023
- Study start21 Apr 2023
- Primary completion28 Feb 2028 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Kessler FoundationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kessler Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Sandroff, Kessler Foundation
- Investigators
- Nancy D Chiaravalloti, PhD, Principal investigator, Kessler Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05716048
- Sponsor's protocol ID
- R-1195-22
- Acronym
- CRUSH-IT
- Status last verified
- Aug 2025
- First submitted
- 13 Jan 2023
- Last updated
- 4 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05716048
- Acronym / sponsor ID
- CRUSH-IT / R-1195-22
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Kessler FoundationUniversity, hospital or other
- Study start
- 21 Apr 2023 (actual)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 8 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KF-mSMT Plus Aerobic Exercise Training | Experimental | Behavioral: KF-mSMT Plus Aerobic Exercise TrainingParticipants 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. |
| KF-mSMT Plus Stretching Exercise Training | Active comparator | Behavioral: KF-mSMT Plus Stretching Exercise TrainingParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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+)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KF-mSMT Plus Aerobic Exercise TrainingParticipants 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 | Behavioural | KF-mSMT Plus Aerobic Exercise Training |
| KF-mSMT Plus Stretching Exercise TrainingParticipants 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 | Behavioural | KF-mSMT Plus Stretching Exercise Training |
Primary outcome
Change in California Verbal Learning Test-3 Performance
Time frame: From 0 to 12 weeks
This is a test of new learning and memory
4 secondary outcomes
Change in hippocampal volume
Time frame: From 0 to 12 weeks
Change in hippocampal activation
Time frame: From 0 to 12 weeks
Change in hippocampal resting-state functional connectivity
Time frame: From 0 to 12 weeks
Change in Everyday Memory Simulations Performance
Time frame: From 0 to 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nancy D Chiaravalloti, PhD principal investigator
Kessler Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KF-mSMT Plus Aerobic Exercise Training and KF-mSMT Plus Stretching Exercise Training in people with Traumatic Brain Injury, run by Kessler Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nancy Moore, MA (973-324.8450, nbmoore@kesslerfoundation.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in California Verbal Learning Test-3 Performance (time frame: From 0 to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2025.