Physical Activity Modifies Exercise Responsiveness

NCT07792967 | Not Yet Recruiting DMC

• 1 other identifier: RRD6-004-25W
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Multimorbidity

Outcome Measures

Primary Outcomes (4)

• Vascular function

  Measured by flow-mediated dilation. Percent dilation (% FMD) from baseline to peak vasodilation. Measured by Doppler Ultrasound.

  pre and post 12 and 24 weeks of intervention

• Muscle Strength

  Isokinetic knee extensor muscle strength.

  pre and post 12 and 24 weeks of intervention

• Physical Activity

  Steps per day.

  pre and post 12 and 24 weeks of intervention

• Sedentary Behavior

  Time spent sedentary measured in hours/day.

  pre and post 12 and 24 weeks of intervention

Study Arms (2)

SLIMM Phase 1

EXPERIMENTAL

Sit less, interact, move more (SLIMM). Goal is to replace time spent sedentary with walking.

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

Dietary Supplement: PB125

Interventions

SLIMM - Sit less, interact, move more BEHAVIORAL

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.

Also known as: SLIMM

SLIMM Phase 1

PB125 DIETARY_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.

PB125/Placebo Phase 2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Multimorbidity Weighted Index \< 6 or \> 11
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

Location

Study Officials

• Joel Douglas Trinity, PhD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joel D Trinity, PhD

CONTACT

(801) 582-1565; Joel.Trinity@va.gov

Breannan Pack, BS

CONTACT

(801) 582-1565; breannan.pack@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants that are non-compliant with SLIMM during phase 1 will transition to either PB125 or placebo. This portion of the trial will be double-blinded and placebo controlled.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)