Clinical trial NCT04638387: PB125, Osteoarthritis, Pain, Mobility, and Energetics
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Osteoarthritis, Knee
Muscle Weakness
Pain, Joint
Lead sponsor: Colorado State University
Sponsor class: OTHER
First posted: 2020-11-20
Enrollment: 4
Sex: ALL
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Mobility-6 min self-paced walk
timeFrame: Change from baseline at 12 weeks
measure: Mobility-sit to stand
timeFrame: Change from baseline at 12 weeks
measure: Mobility-static balance
timeFrame: Change from baseline at 12 weeks
measure: Mobility-6 min fast-paced walk
timeFrame: Change from baseline at 12 weeks
measure: Intermittent and Constant Knee Pain
timeFrame: Change weekly for 12 weeks
measure: Energetics-Submaximal Oxygen Consumption
timeFrame: Change from baseline at 12 weeks
measure: Energetics-Maximal Oxygen Consumption
timeFrame: Change from baseline at 12 weeks
Secondary outcomes:
measure: Energetics-hydrogen peroxide emission
timeFrame: Change from baseline at 12 weeks
measure: Bone Mineral Density
timeFrame: Change from baseline at 12 weeks
measure: Knee Range of Motion
timeFrame: Change from baseline at 12 weeks
measure: Leg extensor strength
timeFrame: Change from baseline at 12 weeks
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Colorado State University
state: Colorado
Study officials:
References: