PB125, Osteoarthritis, Pain, Mobility, and Energetics

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activation, Mobility, and Energetics: A Pilot and Feasibility Clinical Trial of PB125 Treatment for Improving Musculoskeletal and Pain Outcomes in Osteoarthritis

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator in the body. It controls how well cells protect themselves against stress. PB125 (Pathways Bioscience) is a plant based activator of this important regulator Nrf2. PB125 is made up of three plant extracts (rosemary, ashwagandha, and Sophora japonica) so that it contains these things; 1. Carnosol, 2. Withaferin A, and 3. Luteolin. Carnosol comes from rosemary leaves. Rosemary is a spice often used in Italian foods and grown in many herb gardens all around Fort Collins. Withaferin A comes from the medicinal plant Withania somnifera, also called ashwagandha. Ashwaganda is commonly known as "Indian Winter cherry" or "Indian Ginseng" and it is one of the most important herbs of Ayurveda (the traditional system of medicine in India) used for millennia. Finally, luteolin is found widely in plants including those present in the diet (peppers, onions, celery, herbs/spices). Some people purchase these herbs commercially, and take them on their own for a variety of purposes. Typically, when you buy them, they will be in much higher doses than they are in PB125. What makes PB125 different is that very low doses of each of the 3 components work together-synergistically-to activate Nrf2 and increase the ability of cells to respond to stress. It is unknown if there are any benefits to taking PB125 and the risks are currently unknown. The purpose of this study is to examine changes in muscle, in joint pain, in mobility (standing and walking) and in leg strength that occur after consuming PB125 every day for 3 months. We want to make these measurements in people who have been diagnosed with mild to moderate osteoarthritis-a degenerative joint disease-in their knees.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis, Knee; Muscle Weakness; Pain, Joint
• Intervention / Treatment: Dietary supplement: PB125; Dietary supplement: Placebo

Detailed Description

Preventing or slowing age-related decline in musculoskeletal function is important for maintaining mobility and independence. In the US, osteoarthritis (OA) is the primary cause of disability in adults, with no medical or surgical therapeutic intervention known to restore the degenerated cartilage. The loss of skeletal muscle mass and function with age, is also linked to increased risk of other diseases, risk of falls, and decreased quality of life. Therefore, OA and muscle loss together are primary contributors to age-related decreases in mobility and independence. Evidence suggests a decrease in muscle quality is associated with or precedes primary knee OA, suggesting that these two conditions may share a common cause. We will treat 50-65 year old people with mild or moderate OA in both knees, and reported loss of muscle strength, with a supplement already available for use in humans to reduce oxidative stress and inflammation. The supplement is called PB125. In this pilot clinical trial, we will measure the ability of muscle to make energy, measure mobility (walking and standing) and strength, and assess pain following PB125 or placebo treatment.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523-1582
      • Colorado State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• bilateral knee osteoarthritis

Exclusion Criteria:

• smoking
• pregnant/breastfeeding
• BMI >30
• known liver, renal, heart disease, diabetes, autoimmune disease, cancer
• use of methotrexate, etanercept, infliximab, leflunomide, plaquenil
• recent serious illness
• intraarticular stem cell injection
• intraarticular steroid or hyaluronic acid injection within 4 months
• current enrollment in another trial of investigational drugs
• known hypersensitivity to ashwagandha, luteolin, rosemary, or rice flour
• use of anticoagulants or known bleeding disorder
• unwillingness to comply with protocol
• plans for knee replacement in the next 3 years
• unable to complete mobility testing without ambulatory aid
• unable to climb 1-2 flights or stairs without stopping/shortness of breath/discomfort
• blood product transfusion within 30 days
• unable to provide legal consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PB125; Twice daily oral administration of 1 capsule of PB125 (Pathways Bioscience). Treatment will last 12 weeks.	Dietary supplement: PB125; Nrf2 activator containing active ingredients carnosol, withaferin A, and luteolin.
Placebo Comparator: Placebo; Twice daily oral administration of 1 capsule of rice flour placebo (Pathways Bioscience). Treatment will last 12 weeks. Because of pandemic restricting study time frame, enrollment will favor the experimental arm in this pilot study	Dietary supplement: Placebo; Placebo comparator to P125; Other Names: Flour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mobility-6 min self-paced walk	Change in Distance walked	Change from baseline at 12 weeks
Mobility-sit to stand	Change in Time for 5 sit to stand repetitions	Change from baseline at 12 weeks
Mobility-static balance	Yes/No ability to complete 30 sec trials with eyes open or closed on firm and foam surfaces	Change from baseline at 12 weeks
Mobility-6 min fast-paced walk	Change in Distance walked	Change from baseline at 12 weeks
Intermittent and Constant Knee Pain	Weekly change in Intermittent and Constant Pain Score (ICOAP) 11 question survey of pain on a 0-4 scale	Change weekly for 12 weeks
Energetics-Submaximal Oxygen Consumption	Change in oxygen (O2) flux in permeabilized muscle fibers at submaximal adenosine diphosphate (ADP) concentrations	Change from baseline at 12 weeks
Energetics-Maximal Oxygen Consumption	Change in O2 flux in permeabilized muscle fibers at maximal ADP concentrations	Change from baseline at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Energetics-hydrogen peroxide emission	Change in Hydrogen peroxide emission in permeabilized muscle fibers	Change from baseline at 12 weeks
Bone Mineral Density	Bone mineral density via dual x-ray absorptiometry (DEXA)	Change from baseline at 12 weeks
Knee Range of Motion	Change in active and passive bilateral knee range of motion	Change from baseline at 12 weeks
Leg extensor strength	Change in maximal force generated during knee extension	Change from baseline at 12 weeks

Collaborators and Investigators

• Sponsor: Colorado State University

Publications and helpful links

Helpful Links

• Study Flyer on Colorado State University Center for Healthy Aging Website

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 10, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Muscular Diseases; Neuromuscular Manifestations; Osteoarthritis; Arthralgia; Osteoarthritis, Knee; Muscle Weakness
• Other Study ID Numbers: 19-9100H

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No