MultimorbidityNCT07792967
Physical Activity Modifies Exercise Responsiveness
A study testing SLIMM - Sit less, interact, move more and PB125 in people with Multimorbidity, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Exercise is the cornerstone of rehabilitation and an essential part of treatment plans for many chronic conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains incomplete. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multimorbidity
- What is being tested?
- SLIMM - Sit less, interact, move more and PB125
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2027to 31 Dec 2031
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Physically inactive, ≤5,000 steps/day
- Multimorbidity Weighted Index between 6 to 11
- Ability to sign informed consent
- Montreal cognitive assessment (MOCA) exam score ≥26
- Free-living and ambulatory prior to admission
Who cannot join
- Multimorbidity Weighted Index < 6 or > 11
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Currently on a weight-loss diet or body mass index (BMI) > 35 kilograms per square meter (kg/m2) (a BMI of 35 kg/m2, which includes individuals that fall into to the Class I obesity category, has been selected to improve inclusion and generalizability to a greater percentage of the general population)
- Human immunodeficiency virus (HIV) or hepatitis B or C
- Recent anabolic or corticosteroids use (within 3 months)
- Subjects with hemoglobin or hematocrit lower than accepted lab values
- Alcohol abuse (> 2 drinks per day) or drug abuse (inappropriate use of prescription medications or use of any illicit/illegal drugs for recreational use)
- Unwilling to cease dietary supplements 4 weeks prior to initiation intervention
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
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001
Misti R Seppi, MBA BS AAS, (801) 582-1565 ext. 4860, Misti.Seppi@va.gov
P Jon White, MD, (801) 582-1565 ext. 4897, Paul.White2@va.gov
About this study
Official title: Physical Activity Modifies Exercise Responsiveness: Implications for Rehabilitation in Veterans
Exercise is the cornerstone of rehabilitation and an essential part of treatment plans for many chronic conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains incomplete. Physical inactivity and sedentary behavior have reached epidemic levels, coinciding with alarmingly high levels of multimorbidity in Veterans that, the investigators believe, impair exercise responsiveness and rehabilitation efficacy by disrupting the regulation of redox homeostasis and redox signaling by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). This project will use complementary approaches including 1) the Sit Less, Interact, Move More (SLIMM) intervention, and 2) PB125 to target Nrf2 and break the cycle of sedentary behavior, redox stress, functional impairments, and worsening multimorbidity in older Veterans.
Read the detailed description
Significance to VA: Sedentary behavior has emerged as a major risk factor for chronic conditions that are highly prevalent among older Veterans, including obesity, diabetes, and cardiovascular disease Innovation and Impact: Exercise is the cornerstone of rehabilitation and is an essential part of treatment plans for these conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains unclear. Epidemiological findings indicate that adhering to established exercise guidelines does not lower multimorbidity rates or mortality risk in individuals who spend most of their non-exercising time sedentary. Indeed, the negative impact of sedentary behavior on health cannot be offset by exercise alone, highlighting the critical need to prioritize reducing sedentary time in the treatment of age-related diseases. Preliminary data support these epidemiological findings and provide novel evidence that physical inactivity minimizes the beneficial effects of exercise, limiting exercise adaptation and rehabilitation effectiveness. This is particularly concerning as physical inactivity and sedentary behavior continue to increase among older Veterans coinciding with alarming levels of multimorbidity (60-80% of older Veterans have multimorbidity). Although the factors linking physical inactivity and exercise response variability have yet to be identified, aging and multimorbidity are associated with disruptions in redox homeostasis and impaired Nrf2 (nuclear factor erythroid 2-related factor 2) signaling. Nrf2 is a crucial exercise-responsive transcription factor that regulates antioxidant defenses, mitochondrial health, autophagy, and cellular resilience - processes essential for maintaining cellular function during aging. Our central hypothesis is that improving redox homeostasis by decreasing sedentary time or through targeted Nrf2 activation will enhance exercise responsiveness and improve vascular and skeletal muscle function.
Specific Aim 1: Determine the impact of the Sit Less, Interact, Move More (SLIMM) intervention on exercise responsiveness, vascular function, and skeletal muscle function in older Veterans with multimorbidity. Hypothesis: The investigators hypothesize that reducing sedentary behavior and increasing physical activity through SLIMM will restore redox balance and, thereby, improve exercise responsiveness and enhance vascular and skeletal muscle function.
Specific Aim 2: Determine the impact of targeted Nrf2 activation with PB125 on exercise responsiveness, vascular function, and skeletal muscle function in older Veterans with multimorbidity. Hypothesis: The investigators hypothesize that targeted Nrf2 activation will serve as an effective redox-based therapy to enhance exercise responsiveness and promote vascular and skeletal muscle function. Methodology: The investigators will use a SMART (Sequential Multiple Assignment Randomized Trial) study design in which older Veterans with multimorbidity will first undergo our Sit Less, Interact, Move More (SLIMM) intervention to decrease sedentary behavior and increase physical activity. Veterans that are compliant with SLIMM will continue with SLIMM for a total of 24 weeks. Participants that are not compliant with SLIMM will transition to targeted Nrf2 therapy with PB125, a novel and naturally occurring Nrf2 activator, at week 12 and will continue PB125 for 12 weeks. Exercise responsiveness, vascular function, and skeletal muscle function will be examined before and after the SLIMM and PB125 interventions.
Path to Translation/Implementation: This project will provide evidence that redox homeostasis is critical for initiating and coordinating cellular and molecular processes underlying exercise adaptation and improvements in vascular and skeletal muscle health. The impact of this project is high and timely given the alarming rates of multimorbidity among older Veterans and the current gap in effective strategies to enhance physical function and health in this vulnerable population.
- Conditions
- Multimorbidity
- Being tested
- SLIMM - Sit less, interact, move more, PB125
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLIMM - Sit less, interact, move moreBehavioural
Also called SLIMM
To minimize sedentary behavior and increase physical activity the investigators will use our SLIMM intervention. The goal of SLIMM is to replace 1 hour/day of sedentary duration with casual walking time. This goal is ~10% of the average baseline sedentary duration of 10.8 hours/day. While SLIMM is not anchored to a fixed percentage or step count increase, it operationalizes this goal through behavioral coaching and activity monitoring focused on increasing stepping time throughout the day. The SLIMM target duration for decreasing sedentary duration by 1 hour/day is based upon potential impact on energy expenditures and mortality from our previous National Health and Nutrition Examination Survey (NHANES) publication on sedentary behavior in patients with multimorbidity.
PB125Dietary supplement
The novel naturally derived activator of Nrf2, PB125, contains extracts from three botanical sources including i) Rosmarinus officinalis, standardized to carnosol content of 6%, 68 milligrams (mg) of extract; ii) Withania somnifera (aka Ashwagandha), standardized to withaferin A content of 1%, 23 milligrams (mg) of extract; and iii) Sophora Japonica, standardized to luteolin content of 98%, 9 milligrams (mg) of extract. Each extract can increase the nuclear translocation of Nrf2 and when combined, these extracts act in synergy through multiple control points to amplify and prolong the activation of Nrf2.
| Study group | Role | What they receive |
|---|---|---|
| SLIMM Phase 1 | Experimental | Sit less, interact, move more (SLIMM). Goal is to replace time spent sedentary with walking. Receives: Behavioral: SLIMM - Sit less, interact, move more |
| PB125/Placebo Phase 2 | Active comparator | Participants that are not compliant with SLIMM during Phase 1, will under 12 weeks of PB125 or placebo intervention to improve Nrf2 activation and restore redox homeostasis Receives: Dietary Supplement: PB125 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular function
Measured by flow-mediated dilation. Percent dilation (% FMD) from baseline to peak vasodilation. Measured by Doppler Ultrasound.
Measured: pre and post 12 and 24 weeks of intervention
Muscle Strength
Isokinetic knee extensor muscle strength.
Measured: pre and post 12 and 24 weeks of intervention
Physical Activity
Steps per day.
Measured: pre and post 12 and 24 weeks of intervention
Sedentary Behavior
Time spent sedentary measured in hours/day.
Measured: pre and post 12 and 24 weeks of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2026
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MultimorbidityStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The investigators will use a SMART (Sequential Multiple Assignment Randomized Trial) study design in which older Veterans with multimorbidity will first undergo our Sit Less, Interact, Move More (SLIMM) intervention to decrease sedentary behavior and increase physical activity. Veterans that are compliant with SLIMM will continue with SLIMM for a total of 24 weeks. Participants that are not compliant with SLIMM will transition to targeted Nrf2 therapy with PB125, a novel and naturally occurring Nrf2 activator, at week 12 and will continue PB125 for 12 weeks. Exercise responsiveness, vascular unction, and skeletal muscle function will be examined before and after the SLIMM and PB125 interventions.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Joel Douglas Trinity, PhD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07792967
- Sponsor's protocol ID
- RRD6-004-25W
- Status last verified
- Aug 2026
- First submitted
- 20 Aug 2026
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physical Activity Modifies Exercise Responsiveness: Implications for Rehabilitation in Veterans
- ClinicalTrials.gov ID
- NCT07792967
- Acronym / sponsor ID
- RRD6-004-25W
- Conditions
- Multimorbidity
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 28 Aug 2026 (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.
Exercise is the cornerstone of rehabilitation and an essential part of treatment plans for many chronic conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains incomplete. Physical inactivity and sedentary behavior have reached epidemic levels, coinciding with alarmingly high levels of multimorbidity in Veterans that, the investigators believe, impair exercise responsiveness and rehabilitation efficacy by disrupting the regulation of redox homeostasis and redox signaling by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). This project will use complementary approaches including 1) the Sit Less, Interact, Move More (SLIMM) intervention, and 2) PB125 to target Nrf2 and break the cycle of sedentary behavior, redox stress, functional impairments, and worsening multimorbidity in older Veterans.
Detailed description
Significance to VA: Sedentary behavior has emerged as a major risk factor for chronic conditions that are highly prevalent among older Veterans, including obesity, diabetes, and cardiovascular disease Innovation and Impact: Exercise is the cornerstone of rehabilitation and is an essential part of treatment plans for these conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains unclear. Epidemiological findings indicate that adhering to established exercise guidelines does not lower multimorbidity rates or mortality risk in individuals who spend most of their non-exercising time sedentary. Indeed, the negative impact of sedentary behavior on health cannot be offset by exercise alone, highlighting the critical need to prioritize reducing sedentary time in the treatment of age-related diseases. Preliminary data support these epidemiological findings and provide novel evidence that physical inactivity minimizes the beneficial effects of exercise, limiting exercise adaptation and rehabilitation effectiveness. This is particularly concerning as physical inactivity and sedentary behavior continue to increase among older Veterans coinciding with alarming levels of multimorbidity (60-80% of older Veterans have multimorbidity). Although the factors linking physical inactivity and exercise response variability have yet to be identified, aging and multimorbidity are associated with disruptions in redox homeostasis and impaired Nrf2 (nuclear factor erythroid 2-related factor 2) signaling. Nrf2 is a crucial exercise-responsive transcription factor that regulates antioxidant defenses, mitochondrial health, autophagy, and cellular resilience - processes essential for maintaining cellular function during aging. Our central hypothesis is that improving redox homeostasis by decreasing sedentary time or through targeted Nrf2 activation will enhance exercise responsiveness and improve vascular and skeletal muscle function.
Specific Aim 1: Determine the impact of the Sit Less, Interact, Move More (SLIMM) intervention on exercise responsiveness, vascular function, and skeletal muscle function in older Veterans with multimorbidity. Hypothesis: The investigators hypothesize that reducing sedentary behavior and increasing physical activity through SLIMM will restore redox balance and, thereby, improve exercise responsiveness and enhance vascular and skeletal muscle function.
Specific Aim 2: Determine the impact of targeted Nrf2 activation with PB125 on exercise responsiveness, vascular function, and skeletal muscle function in older Veterans with multimorbidity. Hypothesis: The investigators hypothesize that targeted Nrf2 activation will serve as an effective redox-based therapy to enhance exercise responsiveness and promote vascular and skeletal muscle function. Methodology: The investigators will use a SMART (Sequential Multiple Assignment Randomized Trial) study design in which older Veterans with multimorbidity will first undergo our Sit Less, Interact, Move More (SLIMM) intervention to decrease sedentary behavior and increase physical activity. Veterans that are compliant with SLIMM will continue with SLIMM for a total of 24 weeks. Participants that are not compliant with SLIMM will transition to targeted Nrf2 therapy with PB125, a novel and naturally occurring Nrf2 activator, at week 12 and will continue PB125 for 12 weeks. Exercise responsiveness, vascular function, and skeletal muscle function will be examined before and after the SLIMM and PB125 interventions.
Path to Translation/Implementation: This project will provide evidence that redox homeostasis is critical for initiating and coordinating cellular and molecular processes underlying exercise adaptation and improvements in vascular and skeletal muscle health. The impact of this project is high and timely given the alarming rates of multimorbidity among older Veterans and the current gap in effective strategies to enhance physical function and health in this vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The investigators will use a SMART (Sequential Multiple Assignment Randomized Trial) study design in which older Veterans with multimorbidity will first undergo our Sit Less, Interact, Move More (SLIMM) intervention to decrease sedentary behavior and increase physical activity. Veterans that are compliant with SLIMM will continue with SLIMM for a total of 24 weeks. Participants that are not compliant with SLIMM will transition to targeted Nrf2 therapy with PB125, a novel and naturally occurring Nrf2 activator, at week 12 and will continue PB125 for 12 weeks. Exercise responsiveness, vascular unction, and skeletal muscle function will be examined before and after the SLIMM and PB125 interventions.
| Arm | Type | Receives |
|---|---|---|
| SLIMM Phase 1 | Experimental | Behavioral: SLIMM - Sit less, interact, move moreSit less, interact, move more (SLIMM). Goal is to replace time spent sedentary with walking. |
| PB125/Placebo Phase 2 | Active comparator | Dietary Supplement: PB125Participants that are not compliant with SLIMM during Phase 1, will under 12 weeks of PB125 or placebo intervention to improve Nrf2 activation and restore redox homeostasis |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Physically inactive, ≤5,000 steps/day
- Multimorbidity Weighted Index between 6 to 11
- Ability to sign informed consent
- Montreal cognitive assessment (MOCA) exam score ≥26
- Free-living and ambulatory prior to admission
Key exclusion criteria (8 listed)
- Multimorbidity Weighted Index < 6 or > 11
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Currently on a weight-loss diet or body mass index (BMI) > 35 kilograms per square meter (kg/m2) (a BMI of 35 kg/m2, which includes individuals that fall into to the Class I obesity category, has been selected to improve inclusion and generalizability to a greater percentage of the general population)
- Human immunodeficiency virus (HIV) or hepatitis B or C
- Recent anabolic or corticosteroids use (within 3 months)
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 |
|---|---|---|
| SLIMM - Sit less, interact, move moreAlso: SLIMMTo minimize sedentary behavior and increase physical activity the investigators will use our SLIMM intervention. The goal of SLIMM is to replace 1 hour/day of sedentary duration with casual walking time. This goal is ~10% of the average baseline sedentary duration of 10.8 hours/day. While SLIMM is not anchored to a fixed percentage or step count increase, it operationalizes this goal through behavioral coaching and activity monitoring focused on increasing stepping time throughout the day. The SLIMM target duration for decreasing sedentary duration by 1 hour/day is based upon potential impact on energy expenditures and mortality from our previous National Health and Nutrition Examination Survey (NHANES) publication on sedentary behavior in patients with multimorbidity. | Behavioural | SLIMM Phase 1 |
| PB125The novel naturally derived activator of Nrf2, PB125, contains extracts from three botanical sources including i) Rosmarinus officinalis, standardized to carnosol content of 6%, 68 milligrams (mg) of extract; ii) Withania somnifera (aka Ashwagandha), standardized to withaferin A content of 1%, 23 milligrams (mg) of extract; and iii) Sophora Japonica, standardized to luteolin content of 98%, 9 milligrams (mg) of extract. Each extract can increase the nuclear translocation of Nrf2 and when combined, these extracts act in synergy through multiple control points to amplify and prolong the activation of Nrf2. | Dietary supplement | PB125/Placebo Phase 2 |
Primary outcome
Vascular function
Time frame: pre and post 12 and 24 weeks of intervention
Measured by flow-mediated dilation. Percent dilation (% FMD) from baseline to peak vasodilation. Measured by Doppler Ultrasound.
Muscle Strength
Time frame: pre and post 12 and 24 weeks of intervention
Isokinetic knee extensor muscle strength.
Physical Activity
Time frame: pre and post 12 and 24 weeks of intervention
Steps per day.
Sedentary Behavior
Time frame: pre and post 12 and 24 weeks of intervention
Time spent sedentary measured in hours/day.
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 28 Aug 2026.
- 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.
Joel Douglas Trinity, PhD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SLIMM - Sit less, interact, move more and PB125 in people with Multimorbidity, 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 5 inclusion and 8 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: opening soon, as of the sponsor's last update on 28 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 Joel D Trinity, PhD ((801) 582-1565 ext. 1199, Joel.Trinity@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vascular function (time frame: pre and post 12 and 24 weeks of intervention). The study lists 4 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 28 Aug 2026.