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

• Status: Not yet recruiting
• Trial end date: 2027-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The investigators have previously identified knee osteoarthritis patients with the combination of depression and an unhealthy weight may be an increased risk of more rapid joint degeneration and worsening pain. The GetHealthy-OA program combines a mind-body program with the oral supplement fisetin to potentially reduce the risk for this population by treating psychosocial, mechanical, and inflammatory mechanisms of knee osteoarthritis. This randomized clinical trial will compare the GetHealthy-OA program to minimally-enhanced usual care plus an oral placebo.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cale Jacobs, PhD
• Collaborator: Massachusetts General Hospital

Criteria

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)