Overview

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)