Multiple SclerosisCOMBINENCT06197685
A Novel Combinatory Approach to Maximize Functional Recovery of Learning and Memory in Multiple Sclerosis
A study testing The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL) and Stretching and Toning (S/T) in people with Multiple Sclerosis, run by Kessler Foundation at 1 site in United States.
Trial summary
The goal of this novel study is to compare the effect of a combined cognitive rehabilitation and exercise approach on new learning and memory (NLM) in persons with multiple sclerosis (pwMS) and mobility disability. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL) and Stretching and Toning (S/T)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2024to 30 Sep 2027
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be within the ages of 18 and 70 years of age
- Speak English as their primary language
- Confirmed MS diagnosis by a neurologist
- Be relapse and steroid-free for at least 30 days
- Mild-to-moderate self-reported mobility disability, based on the Patient Determined Disease Steps scale (PDDS)
- Currently physically inactive, based on the Godin Leisure Time Exercise Questionnaire (GLTEQ)
- Right handedness
Who cannot join
- History of neurological disorders besides MS or history of uncontrolled psychiatric disorders (ex: major depression)
- Have contraindications to exercise, based on the Physical Activity Readiness Questionnaire (PAR-Q)
- Currently use medications that may impact cognition (ex: steroids, benzodiazepines)
- Currently pregnant
- Contraindication for MRI (metal or electronic devices in the body that are not considered MRI safe)
- Severe cognitive impairment as measured by the Modified Telephone Interview of Cognitive Status (TICS-M)
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
East Hanover, New Jersey, 07936
Carly Wender, PhD, 9732436984, cwender@kesslerfoundation.org
About this study
The goal of this novel study is to compare the effect of a combined cognitive rehabilitation and exercise approach on new learning and memory (NLM) in persons with multiple sclerosis (pwMS) and mobility disability.
Read the detailed description
The proposed research study will be the first to apply the Kessler Foundation modified Story Memory Technique (KF-mSMT®), the practice standard for cognitive rehabilitation, with one of two exercise programs. Alone, KF-mSMT® has been beneficial to NLM impairment, however, its effects are highly selective to list learning and as such, will not maximally restore NLM function. The combination of KF-mSMT® and exercise provides a robust approach towards maximal functional recovery.
- Conditions
- Multiple Sclerosis
- Being tested
- The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL), Stretching and Toning (S/T)
- Keywords
- Multiple Sclerosis, Aerobic exercise, Virtual Reality, Leg cycling, Mobility disability
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Kessler Foundation modified Story Memory Technique® (KF-mSMT®)Behavioural
KF-mSMT is a memory retraining technique that consists of two-related skills: (1) imagery and (2) context/organization. The proposed KF-mSMT intervention includes 10 total sessions with 2 sessions per week for 5 weeks. Each session will last 45-60 minutes.
Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL)Behavioural
Also called IDEAL
The AET condition includes 12 weeks of supervised, progressive, moderate intensity cycle ergometry. The AET will include semi-immersive, interactive VR such the cycling speed on the bike will translate directly to perceived speed through the virtual environment.
Stretching and Toning (S/T)Behavioural
The S/T condition will include 12 weeks of supervised S/T activities that target the head/neck. shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Rehabilitation + Aerobic Exercise with Virtual Reality (VR) | Experimental | In the cognitive rehabilitation and aerobic exercise with VR condition, participants will complete a supervised, aerobic exercise training program (AET) integrated with virtual reality (Ideally Designed Exercise to Accelerate Learning/memory; IDEAL) three days per week over a 12 week period. For seven weeks, participants will only complete IDEAL. For weeks 8-12, participants will complete the Kessler Foundation modified story Memory Technique (KF-mSMT®), a memory retraining program on 2 of the 3 days per week. Receives: Behavioral: The Kessler Foundation modified Story Memory Technique® (KF-mSMT®); Behavioral: Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL) |
| Cognitive Rehabilitation + Stretching and Toning | Experimental | In the cognitive rehabilitation and stretching and toning (S/T) exercise condition, participants will complete 12 weeks of supervised S/T activities 3 days per week over the 12 week period. For seven weeks, participants will only complete S/T. During weeks 8-12, participants will complete the Kessler Foundation modified story Memory Technique (KF-mSMT®), a memory retraining program on 2 of the 3 days per week. Receives: Behavioral: The Kessler Foundation modified Story Memory Technique® (KF-mSMT®); Behavioral: Stretching and Toning (S/T) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in objective new learning and memory (NLM).
The California Verbal Learning Test-Second Edition (CVLT-II) measures verbal learning and memory by having participants recall a list of words from 4 semantic categories. The word list is presented over 5 trials with a 20 minute delayed recall and recognition trial. Standardized T-scores range from 0-100, where higher scores indicated better performance.
Measured: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
Change in everyday memory
The Ecological Memory Simulations (EMS) is a multi-component test that measures memory as it relates to everyday life. Scores range from 0-205, where higher scores indicated better performance.
Measured: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
Secondary outcomes (2)
Change in hippocampal volume
MRI data will be collected in the Rocco Ortenzio Neuroimaging Center at Kessler Foundation using an FDA-approved 3.0 T Siemens Skyra scanner and a 32-channel head coil to measure the volume of bilateral hippocampi.
Measured: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
Change in hippocampal function
fMRI data will be collected during a list-learning task conducted while in the FDA-approved 3.0 T Siemens Skyra scanner with a 32-channel head coil.
Measured: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2024
- Study start12 Feb 2024
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kessler Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Responsible party
- Principal investigator, Carly Wender, Kessler Foundation
- Investigators
- Carly Wender, PhD, Principal investigator, Kessler Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06197685
- Sponsor's protocol ID
- R123323
- Acronym
- COMBINE
- Status last verified
- Aug 2026
- First submitted
- 4 Dec 2023
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Combinatory Approach to Maximize Functional Recovery of Learning and Memory in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06197685
- Acronym / sponsor ID
- COMBINE / R123323
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Aerobic exercise, Virtual Reality, Leg cycling, Mobility disability
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Kessler FoundationUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Study start
- 12 Feb 2024 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 9 Jan 2024 (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.
The goal of this novel study is to compare the effect of a combined cognitive rehabilitation and exercise approach on new learning and memory (NLM) in persons with multiple sclerosis (pwMS) and mobility disability.
Detailed description
The proposed research study will be the first to apply the Kessler Foundation modified Story Memory Technique (KF-mSMT®), the practice standard for cognitive rehabilitation, with one of two exercise programs. Alone, KF-mSMT® has been beneficial to NLM impairment, however, its effects are highly selective to list learning and as such, will not maximally restore NLM function. The combination of KF-mSMT® and exercise provides a robust approach towards maximal functional recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive Rehabilitation + Aerobic Exercise with Virtual Reality (VR) | Experimental | Behavioral: The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Behavioral: Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL)In the cognitive rehabilitation and aerobic exercise with VR condition, participants will complete a supervised, aerobic exercise training program (AET) integrated with virtual reality (Ideally Designed Exercise to Accelerate Learning/memory; IDEAL) three days per week over a 12 week period. For seven weeks, participants will only complete IDEAL. For weeks 8-12, participants will complete the Kessler Foundation modified story Memory Technique (KF-mSMT®), a memory retraining program on 2 of the 3 days per week. |
| Cognitive Rehabilitation + Stretching and Toning | Experimental | Behavioral: The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Behavioral: Stretching and Toning (S/T)In the cognitive rehabilitation and stretching and toning (S/T) exercise condition, participants will complete 12 weeks of supervised S/T activities 3 days per week over the 12 week period. For seven weeks, participants will only complete S/T. During weeks 8-12, participants will complete the Kessler Foundation modified story Memory Technique (KF-mSMT®), a memory retraining program on 2 of the 3 days per week. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Be within the ages of 18 and 70 years of age
- Speak English as their primary language
- Confirmed MS diagnosis by a neurologist
- Be relapse and steroid-free for at least 30 days
- Mild-to-moderate self-reported mobility disability, based on the Patient Determined Disease Steps scale (PDDS)
Key exclusion criteria (6 listed)
- History of neurological disorders besides MS or history of uncontrolled psychiatric disorders (ex: major depression)
- Have contraindications to exercise, based on the Physical Activity Readiness Questionnaire (PAR-Q)
- Currently use medications that may impact cognition (ex: steroids, benzodiazepines)
- Currently pregnant
- Contraindication for MRI (metal or electronic devices in the body that are not considered MRI safe)
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 |
|---|---|---|
| The Kessler Foundation modified Story Memory Technique® (KF-mSMT®)KF-mSMT is a memory retraining technique that consists of two-related skills: (1) imagery and (2) context/organization. The proposed KF-mSMT intervention includes 10 total sessions with 2 sessions per week for 5 weeks. Each session will last 45-60 minutes. | Behavioural | Cognitive Rehabilitation + Aerobic Exercise with Virtual Reality (VR), Cognitive Rehabilitation + Stretching and Toning |
| Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL)Also: IDEALThe AET condition includes 12 weeks of supervised, progressive, moderate intensity cycle ergometry. The AET will include semi-immersive, interactive VR such the cycling speed on the bike will translate directly to perceived speed through the virtual environment. | Behavioural | Cognitive Rehabilitation + Aerobic Exercise with Virtual Reality (VR) |
| Stretching and Toning (S/T)The S/T condition will include 12 weeks of supervised S/T activities that target the head/neck. shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. | Behavioural | Cognitive Rehabilitation + Stretching and Toning |
Primary outcome
Change in objective new learning and memory (NLM).
Time frame: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
The California Verbal Learning Test-Second Edition (CVLT-II) measures verbal learning and memory by having participants recall a list of words from 4 semantic categories. The word list is presented over 5 trials with a 20 minute delayed recall and recognition trial. Standardized T-scores range from 0-100, where higher scores indicated better performance.
Change in everyday memory
Time frame: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
The Ecological Memory Simulations (EMS) is a multi-component test that measures memory as it relates to everyday life. Scores range from 0-205, where higher scores indicated better performance.
2 secondary outcomes
Change in hippocampal volume
Time frame: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
Change in hippocampal function
Time frame: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)
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 5 Aug 2026.
Related trials for Multiple Sclerosis
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
Multiple Sclerosis
RecruitingPhase 2
Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis
Multiple Sclerosis
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.
Carly Wender, 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 study testing The Kessler Foundation modified Story Memory Technique® (KF-mSMT®), Aerobic Exercise Training (AET) plus Virtual Reality (IDEAL) and Stretching and Toning (S/T) in people with Multiple Sclerosis, 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 7 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 5 Aug 2026. 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.
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 Carly Wender, PhD ((973) 324-8388, cwender@kesslerfoundation.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in objective new learning and memory (NLM). (time frame: Weeks 1 and 2 (pre-intervention) and Weeks 15 and 16 (post-intervention)). The study lists 2 primary outcomes in all. 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 5 Aug 2026.