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

NCT ID: NCT05482672

Last Updated: 2023-05-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-30
• Study Completion Date: 2023-04-30

Brief 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.

Detailed Description

The study will employ a double-blind, randomized, placebo-controlled clinical trial to compare the the multimodal GetHealthy-OA program versus placebo. As part of this clinical trial, 120 patients will be randomized to 1 of 2 groups: The GetHealthy-OA program that combines a mind-body program with oral fisetin versus a control group treated with an oral placebo and minimally-enhanced usual care (MEUC). The GetHealthy-OA group will participate in the 6-week the mind-body program and will take oral fisetin for 2 consecutive days (day 1 and 2), a 28-day wash-out period, and then another 2-day course (days 31 and 32). The MEUC group will be given a health education handout at the date of baseline testing and will take an oral placebo for 2 consecutive days (day 1 and 2) and then again 28 days later (days 29 and 30). To determine if immediate improvements are realized and whether gains are sustained after the completing the program, participants will be assessed at baseline, 6 weeks, 3 months, and 6 months.

The GetHealthy-OA mind-body program is a live-video, group program delivered via secure telehealth with mind-body skills to reduce pain and increase physical activity to promote optimal joint loading. The on-line program will be delivered remotely by a psychologist based at Massachusetts General Hospital via Zoom and we will assess symptoms and monitor any technical difficulties. The program consist of 6 sessions that will last about 45 minutes. The sessions are done on your smartphone or computer, and will include a group of 4 to 5 other people with knee arthritis who are also taking part in the study with you at the same time. The GetHealthy-OA group will participate in the 6-week the mind-body program and will take oral fisetin for 2 consecutive days (day 1 and 2), a 28-day wash-out period, and then another 2-day course (days 31 and 32).

The MEUC group will be given a health education booklet at the date of baseline testing and will take an oral placebo (corn starch) for 2 consecutive days (day 1 and 2) and then again 28 days later (days 29 and 30). The booklet will contain brief summarized information that reflects the active intervention topics including the trajectory of pain and recovery for those with knee osteoarthritis, the role of relaxation strategies to manage pain, and the importance of returning to engagement in activities of daily living. The MEUC will be given an oral placebo (corn starch) that is identical to the fisetin capsules with the same dosing regimen as the GetHealthy-OA group. Similar to participants in GetHealthy-OA group, participants in this group will receive usual medical care as determined by the medical team. Usual care involves meetings with physicians, medical staff, and physical therapy. Usual care is identical in intervention and control groups.

Conditions

Knee Osteoarthritis; Obese; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GetHealthy-OA

The GetHealthy-OA program combines a 6-week mind-body program delivered via live video with the oral supplement fisetin. Oral fisetin will be taken for 2 consecutive days (day 1 and 2), a 28-day wash-out period, and then another 2-day course (days 31 and 32).

Group Type: EXPERIMENTAL

Fisetin

Intervention Type: DRUG

Fisetin is a plant flavanol senolytic found in strawberries, persimmons, and cucumbers. This naturally derived senolytic has few side effects and previous animal models of both osteoarthritis and rheumatoid arthritis have demonstrated that the senolytic supplement fisetin reduces inflammation and slows cartilage breakdown.

GetHealthy-OA mind-body program

Intervention Type: BEHAVIORAL

The GetHealthy-OA mind-body program emphasizes increased physical activity, healthy diet and sleep habits to lessen osteoarthritis and depressive symptoms

Minimally Enhanced Usual Care

The minimally enhanced usual care group will be given a health education booklet at the date of baseline testing and will take an oral placebo for 2 consecutive days (day 1 and 2) and then again 28 days later (days 29 and 30).

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

The oral placebo will consist of corn starch and gelatin capsules

Health education booklet

Intervention Type: BEHAVIORAL

The booklet will containing brief summarized information that reflects the active intervention topics including the trajectory of pain and recovery for those with knee osteoarthritis, the role of relaxation strategies to manage pain, and the importance of returning to engagement in activities of daily living

Interventions

Fisetin

Fisetin is a plant flavanol senolytic found in strawberries, persimmons, and cucumbers. This naturally derived senolytic has few side effects and previous animal models of both osteoarthritis and rheumatoid arthritis have demonstrated that the senolytic supplement fisetin reduces inflammation and slows cartilage breakdown.

Intervention Type: DRUG

GetHealthy-OA mind-body program

The GetHealthy-OA mind-body program emphasizes increased physical activity, healthy diet and sleep habits to lessen osteoarthritis and depressive symptoms

Intervention Type: BEHAVIORAL

Placebo oral capsule

The oral placebo will consist of corn starch and gelatin capsules

Intervention Type: DRUG

Health education booklet

The booklet will containing brief summarized information that reflects the active intervention topics including the trajectory of pain and recovery for those with knee osteoarthritis, the role of relaxation strategies to manage pain, and the importance of returning to engagement in activities of daily living

Intervention Type: BEHAVIORAL

Other Intervention Names

Novusetin; 7,3',4'-flavon-3-ol; 3,3',4',7-tetrahydroxyflavone

Eligibility 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)

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Cale Andrew Jacobs, PhD

OTHER

Sponsor Role: lead

Responsible Party

Cale Andrew Jacobs, PhD

Invetigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Cale Jacobs, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

UK Healthcare at Turfland

Lexington, Kentucky, United States

UK HealthCare Joint Reconstruction and Replacement

Lexington, Kentucky, United States

Countries

United States

Other Identifiers

80389

Identifier Type: -

Identifier Source: org_study_id