Have you or your loved ones been diagnosed with pain?
You may be eligible to participate in a pain clinical trial.
Have you or your loved ones been diagnosed with pain? You may be eligible to participate in a pain clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Pain Clinical Trial in Salt Lake City UT
Have you or your loved ones been diagnosed with pain?
You may be eligible to participate in a pain clinical trial.
Have you or your loved ones been diagnosed with pain? You may be eligible to participate in a pain clinical trial.
Completed
Female
25 Years +
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.
Details for the study
Brief Title
Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain
Official Title
A Study to Identify Predictors of Response to Duloxetine in Breast Cancer Patients With Chronic Pain
Brief Summary
Early stage breast cancer is typically treated with surgery, chemotherapy, radiation therapy,<br /> and/or endocrine therapy. Following treatment, 25-60% of breast cancer survivors have<br /> reported chronic pain, which can be difficult to manage. Duloxetine is a serotonin<br /> norepinephrine reuptake inhibitor that is FDA approved for treatment of depression, anxiety,<br /> fibromyalgia, diabetic neuropathic pain, knee arthritis, and low back pain.<br /><br /> Pilot data suggest that duloxetine is effective in management of endocrine therapy-associated<br /> musculoskeletal pain, and a randomized placebo controlled trial of duloxetine has<br /> demonstrated efficacy for treatment of chemotherapy-induced neuropathic pain. In this<br /> mechanistic study of duloxetine, we will investigate the change in pain sensitivity with<br /> treatment in order to evaluate both why duloxetine is effective for management of pain for<br /> some patients, as well as predictors of who is likely to benefit from duloxetine. A total of<br /> 84 women with early stage breast cancer who have chronic pain following treatment, as well as<br /> 48 women who are pain free, will be enrolled. All subjects will undergo assessment of pain<br /> sensitivity and complete questionnaires. Subjects with pain will be treated with duloxetine<br /> for a total of 7 weeks, with pain sensitivity assessments before treatment and after 4 weeks<br /> of full-dose treatment.
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.
Treatments and/or Procedures
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.
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Change in Patient-reported Worst Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Worst pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory. Baseline: Mean worst pain for all individual patients in arm 1 (intervention) and arm 2 (control) 5 weeks: Mean worst pain for all individual patients in arm 1 (intervention) Range of pain score 0-10 (0=no pain; 10=worst pain)
Secondary
Change in Depression Between Baseline and 5 Weeks of Treatment With Duloxetine
Depression will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale. Baseline: Mean depression score for all individual patients in arm 1 (intervention) 5 weeks: Mean depression score for all individual patients in arm 1 (intervention) Range of depression score 0-21 (0=no depression, 21=maximum depression)
Secondary
Change in Objectively Assessed Conditioned Pain Modulation Between Baseline and 5 Weeks of Treatment With Duloxetine
Conditioned pain modulation (CPM) will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing Baseline: Mean CPM for all individual patients in arm 1 (intervention) and arm 2 (control) 5 weeks: Mean CPM for all individual patients in arm 1 (intervention) Range of CPM score: -60 to +60 (more positive values reflect more impaired CPM)
Secondary
Change in Objectively Assessed Pain Sensitivity Between Baseline and 5 Weeks of Treatment With Duloxetine
Pain sensitivity will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing to assess pressure pain threshold (Pain50). Baseline: Mean Pain50 for all individual patients in arm 1 (intervention) and arm 2 (control) 5 weeks: Mean Pain50 for all individual patients in arm 1 (intervention) Range of Pain50 score: 0-10 kg/cm2 (higher number reflects higher pain threshold or lower pain sensitivity)
Secondary
Change in Cognitive Difficulties - Attention/Concentration Between Baseline and 5 Weeks of Treatment With Duloxetine
Cognitive Difficulties - Attention/Concentration will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire. Baseline: Mean attention/concentration score for all individual patients in arm 1 (intervention) 5 weeks: Mean attention/concentration score for all individual patients in arm 1 (intervention) Range of attention/concentration score 0-40 (0=no attention/concentration difficulties, 40=maximum attention/concentration difficulties)
Secondary
Change in Cognitive Difficulties - Visual-Spatial Memory Between Baseline and 5 Weeks of Treatment With Duloxetine
Cognitive Difficulties - Visual-Spatial Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire. Baseline: Mean visual-spatial memory score for all individual patients in arm 1 (intervention) 5 weeks: Mean visual-spatial memory score for all individual patients in arm 1 (intervention) Range of visual-spatial memory score 0-40 (0=no visual-spatial memory difficulties, 40=maximum visual-spatial memory difficulties)
Secondary
Change in Cognitive Difficulties - Verbal Memory Between Baseline and 5 Weeks of Treatment With Duloxetine
Cognitive Difficulties - Verbal Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire. Baseline: Mean verbal memory score for all individual patients in arm 1 (intervention) 5 weeks: Mean verbal memory score for all individual patients in arm 1 (intervention) Range of verbal memory score 0-40 (0=no verbal memory difficulties, 40=maximum verbal memory difficulties)
Secondary
Change in Cognitive Difficulties - Visual-Perceptual Ability Between Baseline and 5 Weeks of Treatment With Duloxetine
Cognitive Difficulties - Visual-Perceptual Ability will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire. Baseline: Mean visual-perceptual ability score for all individual patients in arm 1 (intervention) 5 weeks: Mean visual-perceptual ability score for all individual patients in arm 1 (intervention) Range of visual-perceptual ability score 0-30 (0=no visual-perceptual difficulties, 30=maximum visual-perceptual difficulties)
Secondary
Change in Cognitive Difficulties - Language Between Baseline and 5 Weeks of Treatment With Duloxetine
Cognitive Difficulties - Language will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire. Baseline: Mean language score for all individual patients in arm 1 (intervention) 5 weeks: Mean language score for all individual patients in arm 1 (intervention) Range of language score 0-40 (0=no language difficulties, 40=maximum language difficulties)
Secondary
Change in Patient-reported Average Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Average pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory. Baseline: Mean average pain for all individual patients in arm 1 (intervention) and arm 2 (control) 5 weeks: Mean average pain for all individual patients in arm 1 (intervention) Range of pain score 0-10 (0=no pain; 10=worst pain)
Secondary
Change in Physical Function Between Baseline and 5 Weeks of Treatment With Duloxetine
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. Baseline: Mean physical function T score for all individual patients in arm 1 (intervention) 5 weeks: Mean physical function T score for all individual patients in arm 1 (intervention) Average physical function T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=better physical function)
Secondary
Change in Sleep Disturbance Between Baseline and 5 Weeks of Treatment With Duloxetine
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. Baseline: Mean sleep disturbance T score for all individual patients in arm 1 (intervention) 5 weeks: Mean sleep disturbance T score for all individual patients in arm 1 (intervention) Average sleep disturbance T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=more sleep disturbance)
Secondary
Change in Fatigue Between Baseline and 5 Weeks of Treatment With Duloxetine
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. Baseline: Mean fatigue T score for all individual patients in arm 1 (intervention) 5 weeks: Mean fatigue T score for all individual patients in arm 1 (intervention) Average fatigue T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=more fatigue)
Secondary
Change in Neuropathy Between Baseline and 5 Weeks of Treatment With Duloxetine
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. Baseline: Mean neuropathy score for all individual patients in arm 1 (intervention) 5 weeks: Mean neuropathy score for all individual patients in arm 1 (intervention) Range of neuropathy score 0-44 (0=no neuropathy; 44=most consistent with neuropathy)
Secondary
Change in PainDETECT Score Between Baseline and 5 Weeks of Treatment With Duloxetine
PainDETECT score will be assessed at baseline and 5 weeks for each individual patient using the PainDETECT questionnaire. Baseline: Mean PainDETECT score for all individual patients in arm 1 (intervention) 5 weeks: Mean PainDETECT score for all individual patients in arm 1 (intervention) Range of PainDETECT score -1-38 (-1=no neuropathic pain; 38=most consistent with neuropathic pain)
Secondary
Change in Fibromyalgia Symptom Severity Score Between Baseline and 5 Weeks of Treatment With Duloxetine
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. Baseline: Mean Fibromyalgia Symptom Severity Score for all individual patients in arm 1 (intervention) 5 weeks: Mean Fibromyalgia Symptom Severity Score for all individual patients in arm 1 (intervention) Range of Fibromyalgia Symptom Severity Score 0-12 (0=not consistent with fibromyalgia; 12=most consistent with fibromyalgia)
Secondary
Change in Number of Sites of Pain Between Baseline and 5 Weeks of Treatment With Duloxetine
Number of sites of pain will be assessed at baseline and 5 weeks for each individual patient using the Michigan Body Map. Baseline: Mean number of sites of pain for all individual patients in arm 1 (intervention) 5 weeks: Mean number of sites of pain for all individual patients in arm 1 (intervention) Range of number of sites of pain 0-35 (0=no pain; 35=every pre-defined body site has pain)
Secondary
Change in Pain Interference Between Baseline and 5 Weeks of Treatment With Duloxetine
Pain interference will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory. Baseline: Mean pain interference for all individual patients in arm 1 (intervention) 5 weeks: Mean pain interference for all individual patients in arm 1 (intervention) Range of pain interference score 0-10 (0=no interference; 10=worst interference)
Secondary
Change in Anxiety Between Baseline and 5 Weeks of Treatment With Duloxetine
Anxiety will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale. Baseline: Mean anxiety score for all individual patients in arm 1 (intervention) 5 weeks: Mean anxiety score for all individual patients in arm 1 (intervention) Range of anxiety score 0-21 (0=no anxiety, 21=maximum anxiety)
Study Criteria
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 palbociclib, 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 (SSRI) and tricyclic
antidepressants (TCA) prior to treatment initiation
7. 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
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 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)
3. 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.
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, 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)