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Exercise Plus Duloxetine for Knee Osteoarthritis

Primary Purpose

Knee Osteoarthritis, Depression

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aerobic exercise
Duloxetine
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Knee Osteoarthritis

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Maryland School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Aerobic exercise plus Duloxetine

Arm Description

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.

Outcomes

Primary Outcome Measures

Knee Osteoarthritis Outcomes Scale (KOOS) pain subscale
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)
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

Full Information

First Posted
September 18, 2019
Last Updated
March 21, 2023
Sponsor
University of Maryland, Baltimore
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT04111627
Brief Title
Exercise Plus Duloxetine for Knee Osteoarthritis
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Institute on Aging (NIA)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis, Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aerobic exercise plus Duloxetine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Aerobic exercise
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Intervention Description
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 Measure Information:
Title
Knee Osteoarthritis Outcomes Scale (KOOS) pain subscale
Description
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.
Time Frame
Change from Baseline Pain Severity at 12 weeks
Title
Hamilton Depression Rating Scale (HAM-D)
Description
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.
Time Frame
Change from Baseline Depression Severity at 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: English speaking 40 years or older Symptomatic knee osteoarthritis fulfilling 1986 American College of Rheumatology criteria No plan for surgical knee osteoarthritis intervention within six months of enrollment Major depressive disorder satisfying diagnostic criteria according to the DSM-V Ability to participate in a supervised aerobic exercise program Exclusion Criteria: Already performing aerobic or resistive exercise 2x/week or more Taking duloxetine, antipsychotics, benzodiazepines, or opioid analgesics Other medications deemed by study team to endanger the health of the participant or unduly confound the results Cognitive impairment (Mini-Mental State Examination score < 20) Past or current bipolar disorder or psychotic symptoms according to the DSM-V Substance abuse disorder or suicidal ideation within the previous year 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. Active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy) Pregnant or lactating women Other conditions deemed by study team to endanger the health of the participant or unduly confound the results
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alan M Rathbun, PhD, MPH
Phone
410-706-5151
Email
arathbun@som.umaryland.edu
Facility Information:
Facility Name
University of Maryland School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alan M Rathbun, PhD, MPH
Phone
410-706-5151
Email
arathbun@som.umaryland.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Exercise Plus Duloxetine for Knee Osteoarthritis

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