Moderate Cognitive ImpairmentNCT05117502
Foundations in Developing Precision Cognitive Restoration
A study testing intermittent Theta Burst Stimulation in people with Moderate Cognitive Impairment and Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This pilot study tests the merits of a unique research approach, transdiagnostic sampling. For Veterans with similar levels of cognitive impairments cause by different types of brain injuries (stroke or traumatic brain injury), this study examines effects of two cognitive restorative treatments. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Moderate Cognitive Impairment, Traumatic Brain Injury, Stroke
- What is being tested?
- intermittent Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2022to 30 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of TBI or Ischemic Stroke
- 2-10 years post neurologic event having completed rehabilitation
- Age 18 - 80 years old
- Medically stable
- Fluent in English
- Moderately impaired cognitive function as defined by AMPS Processing sub-scale measures falling below 1.0 logits
- Moderately impaired cognitive capacity as defined by having two or more scores falling 1 standard deviation below age normed expectations on: the RBANS index scores, DKEFS Color-Word Trials 3 and 4 scale scores, and/or WAIS-IV Digit Span scaled score
Who cannot join
- Have BOTH TBI and Ischemic Stroke
- Intracranial lesions or hemorrhagic stroke
- Other primary neurologic diagnosis
- Any dementia diagnosis
- Reside in an extended care facility
- Less than 2 years post TBI or ischemic stroke
Show all 21Show fewer
- Anti-epileptic medications for seizure activity
- Seizure within the past 3 months or active seizure
- Contraindications to MRI/iTBS
- Medication changes within 3 months of starting participation
- Currently receiving therapy services
- Pregnancy
- FIM scores for problem solving <3 or >4 OR memory <4 or >5, or changes in FIM scores during screening process
- Neurostimulants that cannot be safely withdrawn
- Bilateral ischemic stroke
- Mild or severe impairments in cognitive capacity or cognitive function
- CHF, implanted pacemakers or defibrillators, or cochlear implants
- Questionable test validity as indicated by DOT (E-score 17) or BRIEF (Negativity 6; Infrequency 3; Inconsistency 8)
- RBANS Total Scale < 70
- History of/or symptoms of psychotic spectrum disorders (i.e., bipolar, schizophrenia)
- Persons with alcohol use disorder (AUD) and/or substance use disorder (SUD) diagnoses confirmed by clinical and/or scientific experts
Trial locations and contacts
1 site in 1 country.
United States1 site
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-3030
About this study
Official title: Foundational Elements of an Alternate Scientific Approach to Developing Veteran-centric Precision Cognitive Restoration Interventions
This pilot study tests the merits of a unique research approach, transdiagnostic sampling. For Veterans with similar levels of cognitive impairments cause by different types of brain injuries (stroke or traumatic brain injury), this study examines effects of two cognitive restorative treatments. Instead of using the traditional approach to examine treatment effects strictly by cause of brain injury, the transdiagnostic sampling approach recognizes that cause of injury does not drive treatment responsiveness of recovery.
Read the detailed description
The purpose of this study is to identify the supports and barriers to scalability of Veteran-tailored iTBS and APT across neurologic conditions, with the longer-term goal of providing an empirical basis for the tailoring of a broader range of cognitive rehabilitation strategies to optimize each Veteran's cognitive function in daily life. After Veterans receive standard cognitive rehabilitation, cognitive impairments often persist and if they do make gains there is limited carry-over to daily function. The tenets of precision neurorehabilitation suggest that tailored interventions will optimize gains and carry-over, but precision-tailoring of cognitive rehabilitation will only be possible if researchers develop and test scalable approaches for identifying, organizing, and analyzing the multitude of Veteran-specific variables driving and influencing treatment responsiveness. This project addresses long-standing scientific barriers to understanding treatment responsiveness, particularly study sample heterogeneity and individual variability. The investigators address study sample heterogeneity by linking Veterans, across TBI and ischemic stroke, according to levels of cognitive impairment. The investigators create a cohort of Veterans with a homogeneous level of cognitive impairment, thereby enabling explication of person-centric factors influencing treatment responsiveness and carry-over to daily function. Advancing understanding of the basic study design elements will be achieved by leveraging the knowledge of intermittent Theta Burst Stimulation (iTBS) and iTBS paired with Attention Processing Training exercises (iTBS + APT). iTBS is advantageous as it robustly improves working memory with just one treatment session. These interventions, together, are advantageous as they can each be tailored to a Veteran's unique cognitive challenges and to target the neural site, unique to each Veteran's neuropathology. These two interventions also directly address cognitive deficits, while simultaneously inducing neuroplasticity in neural regions hampered or impaired by neural injury. The investigators will study Veterans with moderately impaired cognition who, after standard cognitive rehabilitation, continue to struggle with daily life requiring assistance with complex instrumental activities of daily living (IADL). Veterans will participate in a series of two within-subject treatment studies, conducted on two separate days, 2-weeks apart. Veterans will be randomly assigned to first receive a single session of Active iTBS or Placebo iTBS and then they will receive APT paired with their assigned iTBS (Active iTBS + APT vs Placebo iTBS + APT). The investigators will test if diagnosis moderates the effects of these interventions on both immediate and persisting change in cognition. For immediate effects, the investigators use a novel testing battery and for persisting gains the investigators use established and feasible neuropsychological tests as well as an established test of cognitive function during IADL. Results will be used to obtain pilot data and examine feasibility in terms of study attrition relative to Veteran fatigue, mood, and Veteran reports of suitability of key aspects of the study design. These findings will be used to develop a future merit within-subject cross-over study examining the over-arching hypothesis that tailored iTBS and APT applied to a transdiagnostic sample and subsequently matched to a Veteran, according to a biotype algorithm, will result in better functional performance of Veteran-valued IADL.
- Being tested
- intermittent Theta Burst Stimulation, Placebo intermittent Theta Burst Stimulation
- Keywords
- Pilot projects, Cognition Disorders, Stroke, Brain Injury, Brain Injury, Traumatic, Activities of Daily Living, Working Memory
- Medical subject headings
- Brain Injuries, Traumatic, Stroke, Cognition Disorders, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intermittent Theta Burst StimulationDevice
Also called iTBS, TMS, rTMS
intermittent Theta Burst Stimulation (iTBS) is a type of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered by the MagVenture MagPROX100 with MagOption Stimulator and MagPro Cool Coil B65 A/P. The MagPro Cool Coil B65 A/P can be switched from active to placebo.
Placebo intermittent Theta Burst StimulationDevice
Also called Placebo or Sham TMS, iTMS, rTMS
The placebo coil magnetic stimulation, but does not actually emit a pulse. The placebo coil looks, sounds and feels like an active iTBS coil. The placebo coil, visually identical to the active coil, provides a slight sensory sensation and discharge noise (i.e. clicking) nearly identical to that of the active coil.
| Study group | Role | What they receive |
|---|---|---|
| intermittent Theta Burst Stimulation | Experimental | Participants will receive 2 treatments of intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined iTBS with APT (Attention processing training). Receives: Device: intermittent Theta Burst Stimulation |
| Placebo intermittent Theta Burst Stimulation | Placebo comparator | Placebo iTBS participants will not receive any stimulation as the coil will be switched to placebo (P) setting. To maintain double-blind in A and P settings, Veterans and researchers wear headphones connected to a sham noise generator. Participants will receive 2 treatments of placebo intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined placebo iTBS with APT (Attention processing training). Receives: Device: Placebo intermittent Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Streamlined Assessment of Motor and Process Skills (s-APMS) Change 5 timepoints: before and after 1st and 2nd session, then follow up
Observational assessment by a trained researcher that measures the performance quality of tasks related to activities of daily living in a natural environment. Examples of activities could include light house work, laundry or meal preparation. The sAMPS assesses the quality of the participant's Activity of Daily Living performance by rating effort, efficiency, safety and independence of motor and processing skill items. The performance of these activities are item-level scores ranging from 1=no problem to 6=inordinate, cannot test. This is an observational test and the research clinician interprets AMPS reports to define and interpret reasons for the person's ineffective ADL performance.
Measured: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Secondary outcomes (1)
Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span subtest
Researcher administered verbal assessment use to measure auditory attention as well as working memory. The researcher verbally presents a sequence of numbers to the participant. The participant is to repeat the sequence back to the researcher. The test is administered in three subtest: Digit span forward, Digit Span Backward, and Digit Span Sequencing. Each subtest is scored with correct minus incorrect responses. The final scoring is completed researcher by raw scores and age.
Measured: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start24 Feb 2022
- Primary completion30 Sep 2023
- Study completion30 Sep 2023
Why it stopped: PI Retirement and no one completed the consent process
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Moderate Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All iTBS (intermittent Theta Burst Stimulation) sessions will be double-blinded, but the Attention procession sessions will not. This is a within-subject placebo-controlled partially-blinded treatment study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Theresa L Pape, DrPH MA BS, Principal investigator, Edward Hines Jr. VA Hospital, Hines, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05117502
- Sponsor's protocol ID
- N3751-P
- Status last verified
- Aug 2024
- First submitted
- 12 Oct 2021
- Last updated
- 29 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Foundational Elements of an Alternate Scientific Approach to Developing Veteran-centric Precision Cognitive Restoration Interventions
- ClinicalTrials.gov ID
- NCT05117502
- Acronym / sponsor ID
- N3751-P
- Keywords
- Pilot projects, Cognition Disorders, Stroke, Brain Injury, Brain Injury, Traumatic, Activities of Daily Living, Working Memory
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI Retirement and no one completed the consent process
- Enrolment
- 0 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 24 Feb 2022 (actual)
- Primary completion
- 30 Sep 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 11 Nov 2021 (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.
This pilot study tests the merits of a unique research approach, transdiagnostic sampling. For Veterans with similar levels of cognitive impairments cause by different types of brain injuries (stroke or traumatic brain injury), this study examines effects of two cognitive restorative treatments. Instead of using the traditional approach to examine treatment effects strictly by cause of brain injury, the transdiagnostic sampling approach recognizes that cause of injury does not drive treatment responsiveness of recovery.
Detailed description
The purpose of this study is to identify the supports and barriers to scalability of Veteran-tailored iTBS and APT across neurologic conditions, with the longer-term goal of providing an empirical basis for the tailoring of a broader range of cognitive rehabilitation strategies to optimize each Veteran's cognitive function in daily life. After Veterans receive standard cognitive rehabilitation, cognitive impairments often persist and if they do make gains there is limited carry-over to daily function. The tenets of precision neurorehabilitation suggest that tailored interventions will optimize gains and carry-over, but precision-tailoring of cognitive rehabilitation will only be possible if researchers develop and test scalable approaches for identifying, organizing, and analyzing the multitude of Veteran-specific variables driving and influencing treatment responsiveness. This project addresses long-standing scientific barriers to understanding treatment responsiveness, particularly study sample heterogeneity and individual variability. The investigators address study sample heterogeneity by linking Veterans, across TBI and ischemic stroke, according to levels of cognitive impairment. The investigators create a cohort of Veterans with a homogeneous level of cognitive impairment, thereby enabling explication of person-centric factors influencing treatment responsiveness and carry-over to daily function. Advancing understanding of the basic study design elements will be achieved by leveraging the knowledge of intermittent Theta Burst Stimulation (iTBS) and iTBS paired with Attention Processing Training exercises (iTBS + APT). iTBS is advantageous as it robustly improves working memory with just one treatment session. These interventions, together, are advantageous as they can each be tailored to a Veteran's unique cognitive challenges and to target the neural site, unique to each Veteran's neuropathology. These two interventions also directly address cognitive deficits, while simultaneously inducing neuroplasticity in neural regions hampered or impaired by neural injury. The investigators will study Veterans with moderately impaired cognition who, after standard cognitive rehabilitation, continue to struggle with daily life requiring assistance with complex instrumental activities of daily living (IADL). Veterans will participate in a series of two within-subject treatment studies, conducted on two separate days, 2-weeks apart. Veterans will be randomly assigned to first receive a single session of Active iTBS or Placebo iTBS and then they will receive APT paired with their assigned iTBS (Active iTBS + APT vs Placebo iTBS + APT). The investigators will test if diagnosis moderates the effects of these interventions on both immediate and persisting change in cognition. For immediate effects, the investigators use a novel testing battery and for persisting gains the investigators use established and feasible neuropsychological tests as well as an established test of cognitive function during IADL. Results will be used to obtain pilot data and examine feasibility in terms of study attrition relative to Veteran fatigue, mood, and Veteran reports of suitability of key aspects of the study design. These findings will be used to develop a future merit within-subject cross-over study examining the over-arching hypothesis that tailored iTBS and APT applied to a transdiagnostic sample and subsequently matched to a Veteran, according to a biotype algorithm, will result in better functional performance of Veteran-valued IADL.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- All iTBS (intermittent Theta Burst Stimulation) sessions will be double-blinded, but the Attention procession sessions will not. This is a within-subject placebo-controlled partially-blinded treatment study.
| Arm | Type | Receives |
|---|---|---|
| intermittent Theta Burst Stimulation | Experimental | Device: intermittent Theta Burst StimulationParticipants will receive 2 treatments of intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined iTBS with APT (Attention processing training). |
| Placebo intermittent Theta Burst Stimulation | Placebo comparator | Device: Placebo intermittent Theta Burst StimulationPlacebo iTBS participants will not receive any stimulation as the coil will be switched to placebo (P) setting. To maintain double-blind in A and P settings, Veterans and researchers wear headphones connected to a sham noise generator. Participants will receive 2 treatments of placebo intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined placebo iTBS with APT (Attention processing training). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of TBI or Ischemic Stroke
- 2-10 years post neurologic event having completed rehabilitation
- Age 18 - 80 years old
- Medically stable
- Fluent in English
Key exclusion criteria (21 listed)
- Have BOTH TBI and Ischemic Stroke
- Intracranial lesions or hemorrhagic stroke
- Other primary neurologic diagnosis
- Any dementia diagnosis
- Reside in an extended care facility
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 |
|---|---|---|
| intermittent Theta Burst StimulationAlso: iTBS, TMS, rTMSintermittent Theta Burst Stimulation (iTBS) is a type of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered by the MagVenture MagPROX100 with MagOption Stimulator and MagPro Cool Coil B65 A/P. The MagPro Cool Coil B65 A/P can be switched from active to placebo. | Device | intermittent Theta Burst Stimulation |
| Placebo intermittent Theta Burst StimulationAlso: Placebo or Sham TMS, iTMS, rTMSThe placebo coil magnetic stimulation, but does not actually emit a pulse. The placebo coil looks, sounds and feels like an active iTBS coil. The placebo coil, visually identical to the active coil, provides a slight sensory sensation and discharge noise (i.e. clicking) nearly identical to that of the active coil. | Device | Placebo intermittent Theta Burst Stimulation |
Primary outcome
Streamlined Assessment of Motor and Process Skills (s-APMS) Change 5 timepoints: before and after 1st and 2nd session, then follow up
Time frame: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Observational assessment by a trained researcher that measures the performance quality of tasks related to activities of daily living in a natural environment. Examples of activities could include light house work, laundry or meal preparation. The sAMPS assesses the quality of the participant's Activity of Daily Living performance by rating effort, efficiency, safety and independence of motor and processing skill items. The performance of these activities are item-level scores ranging from 1=no problem to 6=inordinate, cannot test. This is an observational test and the research clinician interprets AMPS reports to define and interpret reasons for the person's ineffective ADL performance.
1 secondary outcome
Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span subtest
Time frame: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Theresa L Pape, DrPH MA BS principal investigator
Edward Hines Jr. VA Hospital, Hines, IL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intermittent Theta Burst Stimulation in people with Moderate Cognitive Impairment and Traumatic Brain Injury, run by VA Office of Research and Development 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 7 inclusion and 21 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: withdrawn, as of the sponsor's last update on 29 Aug 2024. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Streamlined Assessment of Motor and Process Skills (s-APMS) Change 5 timepoints: before and after 1st and 2nd session, then follow up (time frame: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up). 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 29 Aug 2024.