Exercise Plus Duloxetine for Knee Osteoarthritis and Depression

• ClinicalTrials.gov Identifier: NCT04111627
• Recruitment Status: Not yet recruiting
• First Posted: October 1, 2019
• Last Update Posted: October 1, 2019
• Sponsor: University of Maryland, Baltimore
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Alan Rathbun, University of Maryland, Baltimore

Tracking Information

• First Submitted Date: September 18, 2019
• First Posted Date: October 1, 2019
• Last Update Posted Date: October 1, 2019
• Estimated Study Start Date: December 1, 2019
• Estimated Primary Completion Date: November 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2019)

• Knee Osteoarthritis Outcomes Scale (KOOS) pain subscale [ Time Frame: Change from Baseline Pain Severity at 12 weeks ]
  The self-reported KOOS pain subscale is sensitive to changes in knee OA symptoms, and consists of nine items scored on a Likert scale (0 [No problems] to 4 [Extreme Problems]) that ranges from 0-36, with higher values indicating greater severity.
• Hamilton Depression Rating Scale (HAM-D) [ Time Frame: Change from Baseline Depression Severity at 12 weeks ]
  The HAM-D is clinician-administered, 21-item questionnaire, designed to rate the severity of depression in patients. Individual scores are based on the first 17 items, each with a possible score of 0-4 (0=Absent; 4=Extreme Symptoms) or 0-2 (0=Absent; 2=Frequent), yielding an overall range of 0-54. Higher scores indicate greater depression severity.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 30, 2019)

Maximal oxygen consumption [ Time Frame: Change from Baseline Peak Maximal Oxygen Consumption at 12 weeks ]

Peak maximal oxygen consumption will be assessed while patients are walking on a treadmill, when they are respiring through a non-rebreather mask to collect expired air. Carbon dioxide and oxygen gas concentrations will be measured, and the final 20 seconds of oxygen consumption are averaged to determine peak consumption.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Exercise Plus Duloxetine for Knee Osteoarthritis and Depression
• Official Title: A Feasibility and Pilot Study of Combined Treatment Protocol Using Aerobic Exercise and Duloxetine in Older Adults With Symptomatic Knee Osteoarthritis and Comorbid Depression
• Brief Summary: This study evaluates the addition of duloxetine to aerobic exercise in the treatment of symptomatic knee osteoarthritis and depressive symptoms in adults. All participants will receive the receive the treatment protocol, which will first be evaluated in terms of feasibility and then pilot tested.
• Detailed Description: Symptomatic knee osteoarthritis (OA) affects 10% of men and 13% of women 60 years or older, and depressive symptoms are common, occurring in one-fifth of these patients. Depressive symptoms worsen knee OA disease severity and are a barrier to pain management and engagement in physical activity. Guidelines recommend depression treatment in older adults with knee OA but provide no direction on how to simultaneously manage the co-occurrence of physical and mental morbidity. Treatment recommendations advise exercise to manage pain and disability and improve psychosocial health in knee OA patients; however, compliance to exercise programs is low in persons with chronic pain and disability and is only made worse by comorbid depression. Adherence is critical to the efficacy of depression treatments using exercise training, and no such exercise program has ever been designed for and tested in OA patients with co-occurring depressive symptoms in a way to enhance compliance. Duloxetine is the only antidepressant medication indicated for pain management in knee OA patients that has demonstrated efficacy and tolerability when treating depression in older adults and is a viable pharmacological complement to exercise. There are no protocols that combine treatments using interventions that affect symptoms of both knee OA and depression, and the study goals are to evaluate the feasibility of and then pilot test a protocol comprised of aerobic exercise training plus duloxetine for the treatment of symptomatic knee OA and comorbid depression.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Knee Osteoarthritis
• Depression

Intervention

• Behavioral: Aerobic exercise
  Participants with symptomatic knee osteoarthritis and depressive symptoms will be enrolled in a progressive walking program designed to reduce pain and disability and improve psychosocial health.
• Drug: Duloxetine
  Duloxetine is an FDA-approved selective serotonin and norepinephrine reuptake inhibitor antidepressant approved for the treatment of neuropathic pain in symptomatic knee osteoarthritis as well as depression in adults. Participants with symptomatic knee osteoarthritis and depressive symptoms will receive duloxetine to decrease pain and depression severity to enhance their ability to engage in aerobic exercise.

Study Arms

Experimental: Aerobic exercise plus Duloxetine

Participants will have a starting duloxetine dosage of 30 mg/day and be titrated up to a daily optimal dosage of 60 mg/day as tolerated during the first 12-weeks of the study. Twelve weeks after the receipt of their prescription, participants will be evaluated for the need to increase medication dosage to 90 mg/day. After duloxetine initiation, participants will be provided an exercise prescription that includes a progressive walking program aiming to achieve 50 minutes of moderate-intensity physical activity, three times per week, over 24 weeks.

Interventions:

• Behavioral: Aerobic exercise
• Drug: Duloxetine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 30, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 14, 2023
• Estimated Primary Completion Date: November 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age of 40 years or older,
• Symptomatic knee osteoarthritis fulfilling 1986 American College of Rheumatology criteria
• Depressive symptoms meeting threshold screening criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition
• Ability to participate in a supervised aerobic exercise program
• No plan for surgical knee osteoarthritis intervention within six months of enrollment

Exclusion Criteria:

• Not able to participate in a supervised exercise program based on the presence of unstable angina, recent myocardial infarction (within last 3 months), severe silent ischemia, previous stroke with hemiparetic gait, inability to walk at least 1mph on treadmill safely, poorly controlled hypertension (resting blood pressure > 190/110), or peripheral arterial disease with current foot or leg ulcers; exercise tolerance limited by any disease process other than OA (e.g., COPD)
• Active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy)
• Cognitive impairment (Mini-Mental Sate Examination < 20)
• Already performing aerobic or resistive exercise 2x/week or more
• Presence of bipolar, psychotic, substance abuse disorder, or suicidal ideation
• Ever having used antidepressants
• Taking antipsychotics, benzodiazepines, or opioid analgesics
• Current use of Coumadin or other anticoagulants other than low dose aspirin (≤ 325 mg)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alan M Rathbun, PhD, MPH; 410-706-5151; arathbun@som.umaryland.edu

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04111627
• Other Study ID Numbers: HP-00085596; K01AG064041 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Alan Rathbun, University of Maryland, Baltimore
• Study Sponsor: University of Maryland, Baltimore
• Collaborators: National Institute on Aging (NIA)
• Investigators: Not Provided
• PRS Account: University of Maryland, Baltimore
• Verification Date: September 2019