PB125, Osteoarthritis, Pain, Mobility, and Energetics

• ClinicalTrials.gov Identifier: NCT04638387
• Recruitment Status: Recruiting
• First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Sponsor: Colorado State University
• Information provided by (Responsible Party): Karyn Hamilton, Colorado State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee; Muscle Weakness; Pain, Joint	Dietary Supplement: PB125; Dietary Supplement: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Primary comparisons will be between pre-test and post-test measures. We had initially planned control group comparisons as well, but the pandemic has cut this pilot study short of budget and time. Therefore, the primary comparisons will now be pre-test to post-test to maximize the number of participants enrolled to receive the experimental treatment.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Participants will not know if they are receiving PB125 or placebo. Participants will complete pain surveys. Team members making measurements of mobility and mitochondrial energetics will not know if participants or samples are PB125 or placebo.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 3, 2020
• Estimated Primary Completion Date: November 1, 2021
• Estimated Study Completion Date: June 1, 2022

Arms and Interventions

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 Name: Flour

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Karyn Hamilton, PhD; 970-491-3961; Karyn.Hamilton@ColoState.EDU

Contact: Laurie Biela, BS; 970-491-2242; Laurie.Biela@colostate.edu

Locations

United States, Colorado

Colorado State University; Recruiting

Fort Collins, Colorado, United States, 80523-1582

Contact: Karyn Hamilton, PhD 970-491-3961 karyn.hamilton@colostate.edu

Contact: Laurie Biela, BS 970-491-2242 Laurie.Biela@colostate.edu

Principal Investigator: Karyn Hamilton, PhD

Sponsors and Collaborators

Colorado State University

More Information

Additional Information:

Study Flyer on Colorado State University Center for Healthy Aging Website 

• Responsible Party: Karyn Hamilton, Professor, Colorado State University
• ClinicalTrials.gov Identifier: NCT04638387
• Other Study ID Numbers: 19-9100H
• First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Muscle Weakness; Arthralgia; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pain