- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01912612
Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain
A Study to Identify Predictors of Response to Duloxetine in Breast Cancer Patients With Chronic Pain
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, 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.
Study Overview
Detailed Description
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.
Data from a randomized, placebo-controlled clinical trial of duloxetine demonstrated that it is effective in management of both aromatase inhibitor-associated musculoskeletal pain and chemotherapy-induced neuropathic pain. In this mechanistic study, we investigated 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. The original protocol was designed as a randomized, placebo-controlled cross-over trial, with planned enrollment of 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. However because of challenges with logistics of the protocol and pain testing, the trial was redesigned after only 7 patients with pain were enrolled. The new design was a single arm trial, and all patients with pain were treated with duloxetine (no placebo); there was still a non-treatment comparator arm of patients without pain. Patients were enrolled first at the University of Michigan and then the University of Utah. A total of 39 patients with pain and 43 controls without pain were enrolled before the trial closed to enrollment. All subjects underwent assessment of pain sensitivity and completed questionnaires. Subjects with pain were treated with duloxetine for a total of 7 weeks, with pain sensitivity assessments before treatment and after 4 weeks of full-dose treatment. The data from the control patients (who did not receive any study medication) are being compared to those from the patients with pain to understand more about the differences between patients who do and do not experience treatment-related pain, and to interpret the post-intervention patient-reported and pain assessment results.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48103
- University of Michigan Rogel Cancer Center
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- Huntsman Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female patients at least 25 years of age
- 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 palbociclib, pertuzumab, and trastuzumab are permitted.
- Pain that developed or worsened since breast cancer diagnosis and is not due to identifiable traumatic event or fracture
- Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale (assessed verbally)
- Female patients must be at least 1 year postmenopausal or surgically sterile; or must agree to use a medically acceptable form of contraception
- Willing to withdraw from selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) prior to treatment initiation
- Patients who are currently taking non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen, meloxicam, gabapentin, pregabalin) and/or opioid pain medications must remain on a stable dosage throughout the duration of the study
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
- Prior use of duloxetine or milnacipran.
- Prior or current use of venlafaxine specifically for treatment of pain (prior or current use for treatment of other indications, such as hot flashes, is permitted, although cases currently taking venlafaxine must discontinue use prior to study treatment initiation)
- Patients must not be taking any contraindicated medications listed on the duloxetine package insert including the following: phenothiazines, propafenone, flecainide, linezolid, or anticoagulation medication (e.g., heparin, warfarin, or direct oral anticoagulants); treatment with monoamine oxidase inhibitor within 14 days prior to registration.
- Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or artificial nails) that are likely to alter pain perception during testing
- Peripheral sensory neuropathy at the thumbs bilaterally that interferes with function and/or activities of daily living
- Significant risk of suicide based on the Investigator's judgment
- History or behavior that would, in the Investigator's judgment, prohibit compliance for the duration of the study.
- History of alcohol or other substance abuse or dependence within the year prior to registration
- Known chronic liver disease, end stage renal disease, or creatinine clearance <30 mL/min as defined by Cockcroft-Gault equation
- Uncontrolled narrow-angle glaucoma.
- Clinically significant coagulation disorder
- History of seizure disorder
- Pregnant or breast-feeding. Urine pregnancy test will be assessed at the baseline visit in women of child-bearing potential with chronic pain.
- Unable to take oral medications or any medical condition that would interfere with the absorption of study medication capsules.
- Currently taking SSRI, serotonin-norepinephrine reuptake inhibitor (SNRI), or TCA regimen (including Wellbutrin) for treatment of major depressive disorder or generalized anxiety disorder (without approval and involvement of the patient's treating psychiatrist to taper cases off these medications prior to study treatment).
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm 1 (Patients with pain, duloxetine)
Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks.
|
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 Names:
|
NO_INTERVENTION: Arm 2 (Patients without pain -- control)
Patient reported pain and symptoms assessment for comparison at baseline.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Patient-reported Worst Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Worst pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.
|
5 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Patient-reported Average Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Average pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.
|
5 weeks
|
Change in Pain Interference Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Pain interference will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.
|
5 weeks
|
Change in Number of Sites of Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Number of sites of pain will be assessed at baseline and 5 weeks for each individual patient using the Michigan Body Map.
|
5 weeks
|
Change in Fibromyalgia Symptom Severity Score Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Fibromyalgia Symptom Severity Score will be assessed at baseline and 5 weeks for each individual patient using the Michigan Body Map and Symptom Severity Scale.
|
5 weeks
|
Change in PainDETECT Score Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
PainDETECT score will be assessed at baseline and 5 weeks for each individual patient using the PainDETECT questionnaire.
|
5 weeks
|
Change in Neuropathy Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Neuropathy will be assessed at baseline and 5 weeks for each individual patient using the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) questionnaire.
|
5 weeks
|
Change in Fatigue Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Fatigue will be assessed at baseline and 5 weeks for each individual patient using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.
|
5 weeks
|
Change in Sleep Disturbance Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Sleep Disturbance will be assessed at baseline and 5 weeks for each individual patient using the PROMIS Sleep Disturbance Short Form 8b v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.
|
5 weeks
|
Change in Physical Function Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Physical Function will be assessed at baseline and 5 weeks for each individual patient using the PROMIS Physical Function Short Form 10a v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.
|
5 weeks
|
Change in Anxiety Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Anxiety will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale.
|
5 weeks
|
Change in Depression Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Depression will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale.
|
5 weeks
|
Change in Cognitive Difficulties - Language Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Cognitive Difficulties - Language will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.
|
5 weeks
|
Change in Cognitive Difficulties - Visual-Perceptual Ability Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Cognitive Difficulties - Visual-Perceptual Ability will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.
|
5 weeks
|
Change in Cognitive Difficulties - Verbal Memory Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Cognitive Difficulties - Verbal Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.
|
5 weeks
|
Change in Cognitive Difficulties - Visual-Spatial Memory Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Cognitive Difficulties - Visual-Spatial Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.
|
5 weeks
|
Change in Cognitive Difficulties - Attention/Concentration Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Cognitive Difficulties - Attention/Concentration will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.
|
5 weeks
|
Change in Objectively Assessed Pain Sensitivity Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Pain sensitivity will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing to assess pressure pain threshold (Pain50).
|
5 weeks
|
Change in Objectively Assessed Conditioned Pain Modulation Between Baseline and 5 Weeks of Treatment With Duloxetine
Time Frame: 5 weeks
|
Conditioned pain modulation (CPM) will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing
|
5 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Lynn Henry, MD, PhD, University Of Michigan
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pain
- Neurologic Manifestations
- Chronic Pain
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Serotonin and Noradrenaline Reuptake Inhibitors
- Duloxetine Hydrochloride
Other Study ID Numbers
- UMCC 2013.044
- HUM00075181 (OTHER: University of Michigan)
- HCI94979 (OTHER: University of Utah)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pain
-
Flowonix MedicalApproved for marketingBack Pain | Leg Pain | Trunk Pain | Intractable Pain | Arm Pain
-
University Hospital Schleswig-HolsteinZealand University Hospital; European Regional Development Fund; Design School...CompletedPain, Acute | Pain, Chronic | Pain Measurement | Pain, CancerGermany
-
Dr. Negrin University HospitalCompletedPostoperative Pain, Acute | Postoperative Pain, ChronicSpain
-
George Washington UniversityRecruitingCervical Fusion | Pain, Back | Pain, Neck | Myofacial PainUnited States
-
Dow University of Health SciencesRecruitingLow Back Pain | Chronic Low-back Pain | Low Back Pain, Mechanical | Mechanical Low Back Pain | Pain, Chronic | Pain, Back | Lower Back Pain Chronic | CLBP - Chronic Low Back PainPakistan
-
Universitat Jaume ICompletedPain, Acute | Pain, Chronic | OncologySpain
-
Atatürk Chest Diseases and Chest Surgery Training...RecruitingPostoperative Pain | Postoperative Pain, Acute | Postoperative Pain, Chronic | VATSTurkey
-
Janssen Research & Development, LLCCompletedPain, Radiating | Pain, Burning | Pain, Crushing | Pain, Migratory | Pain, SplittingUnited States, France, Spain, Poland, Portugal
-
susanne beckerSNSFCompletedLow Back Pain | Pain, Acute | Pain, ChronicSwitzerland
-
University of Campinas, BrazilCompletedPREGNANCY | LUMBAR BACK PAIN | PELVIC PAIN
Clinical Trials on Duloxetine
-
Shanghai Mental Health CenterJiangsu Nhwa Pharmaceutical Co., Ltd.Completed
-
Boehringer IngelheimCompletedDiabetic Neuropathies | Depressive Disorder, MajorGermany
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.RecruitingMajor Depressive Disorder (MDD)China
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Completed
-
University of MinnesotaHoffmann-La Roche; Minnesota Medical FoundationCompleted
-
University of PittsburghEli Lilly and Company; National Institutes of Health (NIH)CompletedBack Pain | Major Depressive Disorder | AgedUnited States
-
Hamilton Health Sciences CorporationSt. Joseph's Healthcare Hamilton; Eli Lilly and Company; McMaster UniversityUnknown
-
New York State Psychiatric InstituteEli Lilly and CompanyCompletedDysthymic Disorder | Depressive Disorder NOSUnited States
-
Eli Lilly and CompanyShionogiCompleted
-
Boehringer IngelheimCompleted