GetHealthy-OA: A Program to Improve Pain and Function for Patients With Knee Osteoarthritis, Obesity, and Depression

This is an interventional treatment trial for Knee Osteoarthritis Read More

Inclusion Criteria:

• Mild to moderate knee osteoarthritis (Kellgren/Lawrence Grade II or III)
• Obesity (Body Mass Index > 30 kg/m2)
• History of concurrent psychotropics for < 2 weeks prior to initiation of treatment or on stable doses for > 6 weeks
• Access to an internet-enabled computer/smart phone
• Willingness to comply with the study protocol and assessments
• Cleared by a medical doctor to participate

Exclusion Criteria:

• Rheumatoid arthritis
• History of cancer within 5 years of screening; unable to walk/wheelchair-bound
• Prior surgical fixation of a femur or tibia fracture
• Taking high doses of opioid pain medication (>50 milligrams of morphine equivalent per day)
• Diagnosis of a medical illness expected to worsen in the next 6 months (e.g., malignancy)
• Active suicidal ideation or past-year psychiatric hospitalization; non-English speaking
• Lifetime history of schizophrenia, bipolar disorder, or other psychotic disorder
• Current substance abuse or dependence (or a history within the past 6 months)
• Practice of yoga/meditation, or other mind body techniques once per week > 45 min within the last 3 months
• Engagement in regular moderate or vigorous physical exercise for >30 min daily
• Reduced or altered capacity due to administration of any mind-altering substances such as tranquilizers, conscious sedation or anesthesia, or brain injury
• Females who are nursing, pregnant or planning to become pregnant during the duration of study drug dosing

• Females or males who do not wish to abstain from sex or use contraceptive protection during study drug dosing and for 2 weeks after the last dose

  o Those not willing to use 2 of the following effective forms of contraception: sterilization surgery, intrauterine device (IUD), implantable rod, contraceptive shot/injection, oral contraceptives, patch, vaginal ring, diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, and/or a male or female condom

• Subjects who do not have the capacity to consent themselves
• Subjects who are unable to tolerate oral medication

• Subjects having previously undergone any of the following treatments in the stated time window.

  • Surgery on the Study Knee in the past 6 months
  • Partial or complete joint replacement in the study knee. Partial or complete joint replacement in the contralateral knee is acceptable as long as the surgery was performed at least 6 months prior to enrollment and the operative knee is asymptomatic
  • Patients who have undergone arthroscopic surgery (including microfracture and meniscectomy) on the Study Knee in the last 2 years prior to the Screening visit or are anticipated to have arthroscopic surgery on either knee at any time during the study period
  • Currently taking Losartan
  • Currently taking Warfarin or related anticoagulants
  • Senolytic agents taken within the past 6 months and are not willing to discontinue these medications through the duration of the study, including: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax
  • Drugs that induce significant cellular stress and are not willing to discontinue these medications through the duration of the study, including alkylating agents, anthracyclines, platins, other chemotherapy drugs
  • Medications that are sensitive substrates or substrates with a narrow therapeutic range for cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 2 subfamily C member 19 (CYP2C19), cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), Organic Anion Transporting Polypeptide 1B1 (OATP1B1) or strong inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4; e.g. cyclosporine, tacrolimus or sirolimus)
  • Subjects taking the following other drugs if they cannot be held (per the Medical Director Austin Stone, MD, PhD) for at least 2 days before and during administration of Fisetin: cyclosporine, tacrolimus, repaglinide, and bosentan
  • Significant liver disease (i.e. greater than or equal to 2x the upper limit of normal bilirubin levels) or as in the opinion of the Medical Director
  • Significant renal disease (estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m2) or as in the opinion of the Medical Director
  • History of other formally diagnosed joint diseases including osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Cushing's syndrome, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, or neuropathic arthropathy of any cause
  • Patients with type 1 or 2 diabetes (Hemoglobin A1c (HbA1c) > 6.5%) and/or taking medications that affect insulin levels, including: Metformin (within the last week), Glucocorticoids (within the last month), Acarbose (within the last week)