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Exercise Plus Duloxetine for Knee Osteoarthritis and Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04111627
Recruitment Status : Not yet recruiting
First Posted : October 1, 2019
Last Update Posted : January 26, 2021
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Alan Rathbun, University of Maryland, Baltimore

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.

Condition or disease Intervention/treatment Phase
Knee Osteoarthritis Depression Behavioral: Aerobic exercise Drug: Duloxetine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 1, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : February 28, 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.
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.

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. English speaking
  2. 40 years or older
  3. Symptomatic knee osteoarthritis fulfilling 1986 American College of Rheumatology criteria
  4. No plan for surgical knee osteoarthritis intervention within six months of enrollment
  5. Major depressive disorder satisfying diagnostic criteria according to the DSM-V
  6. Ability to participate in a supervised aerobic exercise program

Exclusion Criteria:

  1. Already performing aerobic or resistive exercise 2x/week or more
  2. Taking antidepressants, antipsychotics, benzodiazepines, or opioid analgesics
  3. Other medications deemed by study team to endanger the health of the participant or unduly confound the results
  4. Cognitive impairment (Mini-Mental State Examination score < 20)
  5. Past or current bipolar disorder or psychotic symptoms according to the DSM-V
  6. Substance abuse disorder or suicidal ideation within the previous year
  7. Not able to participate in a supervised exercise program based on the presence of unstable angina, recent MI (within last 3 months), hemiparetic gait, inability to walk at least 1mph on treadmill safely, poorly controlled hypertension (resting blood pressure > 190/110), peripheral arterial disease with current foot or leg ulcers, or cardiac or pulmonary disease with exercise tolerance NYHA class 3 or higher.
  8. Active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy)
  9. Pregnant or lactating women
  10. Other conditions deemed by study team to endanger the health of the participant or unduly confound the results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04111627

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Contact: Alan M Rathbun, PhD, MPH 410-706-5151

Sponsors and Collaborators
University of Maryland, Baltimore
National Institute on Aging (NIA)
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Responsible Party: Alan Rathbun, Assistant Professor, University of Maryland, Baltimore Identifier: NCT04111627    
Other Study ID Numbers: HP-00085596
K01AG064041 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: January 26, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Osteoarthritis, Knee
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Duloxetine Hydrochloride
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Psychotropic Drugs
Dopamine Agents