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

NCT05482672 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 80389
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Knee Osteoarthritis; Obese; Depression

Outcome Measures

Primary Outcomes (3)

• Change in Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC)

  The WOMAC is a self-administered questionnaire consisting of 24 items that is widely used in the evaluation of Hip and Knee Osteoarthritis. Scores range from 0 to 96 with lower scores being indicative of less severe osteoarthritis symptoms

  Change between Baseline and 3 months

• Change in Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference

  The PROMIS Pain Interference (Short Form 8a v1.0) assesses the consequences of pain on relevant aspects of a person's life including the extent to which pain limits engagement with social, cognitive, emotional, physical, and recreational activities. Scores range from 0 to 100 with greater scores indicative of greater pain interference

  Change between Baseline and 3 months

• Change in Average Daily Step Count

  ActiGraph wGT3X-BTLink accelerometer (ActiGraph, LLC, Fort Walton Beach, FL, USA) will be used to assess average step count over a 7-day period at baseline and the 3 post-intervention time points. This accelerometer is widely used to ecologically assess physical functioning outcomes in chronic pain and older adult trials

  Change between Baseline and 3 months

Secondary Outcomes (11)

• Change in serum Interleukin-17 (IL-17)

  Change between Baseline and 6-weeks, 3-months, and 6-months

• Change in serum IL-4

  Change between Baseline and 6-weeks, 3-months, and 6-months

• Change in urinary C-terminal crosslinked telopeptide type II collagen (CTX-II)

  Change between Baseline and 6-weeks, 3-months, and 6-months

• Change in serum Chondroitin Sulfate epitope 846 (CS846)

  Change between Baseline and 6-weeks, 3-months, and 6-months

• Change in Pain Numerical Rating Scale

  Change between Baseline and 6-weeks, 3-months, and 6-months

Study Arms (2)

GetHealthy-OA

EXPERIMENTAL

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).

Drug: Fisetin; Behavioral: GetHealthy-OA mind-body program

Minimally Enhanced Usual Care

PLACEBO COMPARATOR

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).

Drug: Placebo oral capsule; Behavioral: Health education booklet

Interventions

Fisetin 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.

Also known as: Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavone

GetHealthy-OA

GetHealthy-OA mind-body program BEHAVIORAL

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

GetHealthy-OA

Placebo oral capsule DRUG

The oral placebo will consist of corn starch and gelatin capsules

Minimally Enhanced Usual Care

Health education booklet 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

Minimally Enhanced Usual Care

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cale Andrew Jacobs, PhD: lead
• Massachusetts General Hospital: collaborator

Study Sites (2)

UK Healthcare at Turfland

Lexington, Kentucky, 40504, United States

Location

UK HealthCare Joint Reconstruction and Replacement

Lexington, Kentucky, 40508, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Obesity; Depression

Interventions

fisetin

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Cale Jacobs, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study pharmacist that prepared the randomization schedule will meet with the pre-specified unblinded study personnel prior to the site initiation visit. The unblinded personnel will then prepare sealed envelopes that contain each subject's group assignment. The investigators will designate, a priori, study personnel that will be unblinded. These unblinded personnel will be directly involved with maintaining the drug log and communicating with participants to schedule virtual mind-body sessions. The unblinded pharmacist/coordinator will access the actual treatment assignment but both blinded study personnel and the patient will not know the patient's treatment assignment. The Investigator, participant, patient assessors, laboratory personnel, and statistician will remain blinded throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Invetigator

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 1, 2022
• Study Start: April 1, 2023
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: May 1, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)