Mechanistic Study of Duloxetine Versus Placebo in Breast Cancer Patients With Chronic Pain

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: NCT01912612
Recruitment Status : Recruiting
First Posted : July 31, 2013
Last Update Posted : October 3, 2018
American Cancer Society, Inc.
Information provided by (Responsible Party):
University of Utah

Brief Summary:

Early stage breast cancer is typically treated with surgery, chemotherapy, radiation therapy, and/or endocrine therapy. Following treatment, 25-60% of breast cancer survivors have reported chronic pain, which can be difficult to manage. Duloxetine is a serotonin norepinephrine reuptake inhibitor that is FDA approved for treatment of depression, anxiety, fibromyalgia, diabetic neuropathic pain, knee arthritis, and low back pain.

Pilot data suggest that duloxetine is effective in management of endocrine therapy-associated musculoskeletal pain, and a randomized placebo controlled trial of duloxetine has demonstrated efficacy for treatment of chemotherapy-induced neuropathic pain. In this mechanistic study of duloxetine versus placebo, we will investigate the change in pain sensitivity with treatment in order to evaluate both why duloxetine is effective for management of pain for some patients, as well as predictors of who is likely to benefit from duloxetine. A total of 84 women with early stage breast cancer who have chronic pain following treatment, as well as 48 women who are pain free, will be enrolled. All subjects will undergo assessment of pain sensitivity and complete questionnaires. Subjects with pain will be treated with duloxetine for a total of 7 weeks, with pain sensitivity assessments before treatment and after 4 weeks of full-dose treatment.

Condition or disease Intervention/treatment Phase
Pain Drug: Duloxetine Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study to Identify Predictors of Response to Duloxetine in Breast Cancer Patients With Chronic Pain
Actual Study Start Date : August 2013
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm 1
Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks.
Drug: Duloxetine
Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.
Other Name: Cymbalta

Primary Outcome Measures :
  1. Change in patient-reported pain between baseline and 5 weeks of treatment with duloxetine [ Time Frame: 5 weeks ]
    Subjects will be treated with duloxetine for 5 weeks followed by a 2 week taper off the drug. Change in pain between baseline and 5 weeks for each individual patient will be determined.

Secondary Outcome Measures :
  1. Change in objectively assessed pain sensitivity between baseline and 5 weeks of treatment with duloxetine [ Time Frame: 5 weeks ]
    Subjects will be treated with duloxetine for 5 weeks followed by a 2 week taper off the drug. Change in pain sensitivity between baseline and 5 weeks for each individual patient will be assessed using quantitative sensory testing.

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients at least 25 years of age
  2. Diagnosis of stage 0-III breast cancer within 12 years prior to enrollment. All indicated surgery, chemotherapy, and/or radiation therapy must have been completed at least 12 weeks prior to enrollment. Concomitant endocrine therapy and targeted therapies such as pablociclib, pertuzumab, and trastuzumab are permitted.
  3. Pain that developed or worsened since breast cancer diagnosis and is not due to identifiable traumatic event or fracture
  4. Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale (assessed verbally)
  5. Female patients must be at least 1 year postmenopausal or surgically sterile; or must agree to use a medically acceptable form of contraception
  6. Willing to withdraw from selective serotonin reuptake inhibitors and tricyclic antidepressants prior to treatment initiation
  7. Patients who are currently taking non-steroidal anti-inflammatory drugs and/or opioid pain medications must remain on a stable dosage throughout the duration of the study
  8. Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  1. Prior use of duloxetine or milnacipran.
  2. Prior use of venlafaxine specifically for treatment of pain (prior use for treatment of other indications, such as hot flashes, is permitted)
  3. Patients must not be taking any contraindicated medications listed on the duloxetine package insert including the following: phenothiazines, propafenone, flecanide, linezolid, or anticoagulation medication (e.g., heparin, warfarin); treatment with MAO inhibitor within 14 days prior to registration.
  4. Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or artificial nails) that are likely to alter pain perception during testing
  5. Peripheral sensory neuropathy at the thumbs bilaterally that interferes with function and/or activities of daily living
  6. Significant risk of suicide based on the Investigator's judgment
  7. History or behavior that would, in the Investigator's judgment, prohibit compliance for the duration of the study.
  8. History of alcohol or other substance abuse or dependence within the year prior to registration
  9. Known chronic liver disease, end stage renal disease, or creatinine clearance <30 mL/min as defined by Cockcroft-Gault equation
  10. Uncontrolled narrow-angle glaucoma.
  11. Clinically significant coagulation disorder
  12. History of seizure disorder
  13. Pregnant or breast-feeding. Urine pregnancy test will be assessed at the baseline visit in women of child-bearing potential with chronic pain.
  14. Unable to take oral medications or any medical condition that would interfere with the absorption of study medication capsules.
  15. Currently taking SSRI, SNRI, or TCA regimen for treatment of major depressive disorder or generalized anxiety disorder (without approval and involvement of the patient's treating psychiatrist).

Controls are patients without chronic pain who otherwise meet the following eligibility criteria (inclusion #1, 2, 8, exclusion #1, 2, 4, 5, worst pain score 0-1, and not currently on medication for pain)

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): NCT01912612

Contact: Amanda Behunin 801-587-4323

United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Amanda Behunin    801-587-4323   
Principal Investigator: Norah L Henry, MD, PhD         
Sponsors and Collaborators
University of Utah
American Cancer Society, Inc.
Principal Investigator: Norah L Henry, MD, PhD Huntsman Cancer Institute

Responsible Party: University of Utah Identifier: NCT01912612     History of Changes
Other Study ID Numbers: HCI94979
First Posted: July 31, 2013    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by University of Utah:
Breast cancer
Pain sensitivity

Additional relevant MeSH terms:
Duloxetine Hydrochloride
Breast Neoplasms
Chronic Pain
Neoplasms by Site
Breast Diseases
Skin Diseases
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
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