Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment of Patients With Diabetic Peripheral Neuropathic Pain in China: Duloxetine Versus Placebo
Brief Summary: The purpose of this trial is to assess the efficacy of duloxetine 60 milligrams (mg) once daily (QD) compared with placebo, on the change in pain severity from baseline to 12 weeks as measured by the weekly mean of the daily pain scores recorded in the participant's diary in participants with diabetic peripheral neuropathic pain.


Options:
A: Inclusion Criteria:

* Present with pain due to bilateral peripheral neuropathy

  * Participants must have pain caused by Type 1 or Type 2 diabetes mellitus
  * Pain must begin in the feet with relatively symmetrical onset
  * Daily pain should be present for at least 6 months
  * Diagnosis must be confirmed by a score of at least 3 on the Michigan Neuropathy Screening Inventory (MNSI)
* Females must test negative for a serum pregnancy test at Screening. Females of child-bearing potential (who are not surgically sterilized and between menarche and 1 year postmenopause) must agree to use a medically acceptable and reliable means of birth control, during the study and for 1 month following the last study dose.
* Stable glycemic control as assessed by a physician investigator and a glycosylated hemoglobin (HbA1c) \<12% before randomization
* Score of greater than or equal to 4 on the Brief Pain Inventory (BPI) 24-hour average pain item at Screening.
* Full completion of the daily diaries for at least 80% of the days between the second and third time you come to the hospital (Screening).

Exclusion Criteria:

* Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
* Current (less than or equal to 1 year) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I diagnosis of major depressive disorder, dysthymia, anxiety disorders (excluding phobias), alcohol or eating disorders as determined by the Mini-International Neuropsychiatric Interview (MINI) or a previous diagnosis
* DSM-IV diagnosis of mania, bipolar disorder, or psychosis determined either by participant history or by diagnosis using specific MNSI modules
* Serious or unstable cardiovascular, hepatic, renal, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychological conditions that in the opinion of investigator would compromise participation or be likely to lead to hospitalization during the course of the study.
* At Screening alanine transaminase (ALT) greater than 2 times upper limit of normal (ULN), based on central laboratory reference ranges times ULN, based on central laboratory reference ranges
* Prior renal transplant, current renal dialysis, or serum creatinine laboratory value \>1.5 times ULN, based on central laboratory reference ranges at Screening.
* Historical exposure to drugs known to cause neuropathy, or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy
* Pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the diabetic neuropathy pain. Examples of painful conditions that could be confused with diabetic neuropathy pain include peripheral vascular disease, neurological disorders unrelated to diabetic neuropathy, skin condition in the area of the neuropathy that could alter sensation, other painful conditions
* Participants who have previously completed or withdrawn from this study or have been previously treated with duloxetine, including participants who participated in study F1J-MC-HMEQ (NCT00408993), even those in the placebo arm
* Participants taking excluded medications that cannot be stopped at Screening
* Treatment with a monoamine oxidase inhibitor (MAOI) or fluoxetine within 30 days of the third Screening
* Participants with a positive Hepatitis B surface antigen and/or Hepatitis C antibody are to be excluded if they have any of the following:

  * Hepatic dysfunction as determined by the investigator or
  * Clinical manifestations of liver disease within the previous year such as unexplained pruritus, unexplained dark urine, jaundice, unexplained right upper quadrant tenderness, unexplained "flu-like" symptoms or
  * Aspartate transaminase (AST), ALT, or bilirubin above the normal reference range.
B: Inclusion Criteria:

1. Must be between the ages of 18 to 65 years of age
2. Must have been diagnosed with fibromyalgia by a rheumatologist
3. Must have an overall body pain average score ≥ 4
4. Must be on stable doses of your current medication for at least past four weeks
5. Must report all medication including herbal supplements and over-the-counter medications that you are currently taking to a member of the research team.
6. Must limit any changes in your medication(s)during the 21-week study time period unless medically necessary
7. Must be willing to maintain a medication diary provided to you during the 21-week study period
8. Must be willing to abstain (not take) any fibromyalgia related medication (including over-the-counter)for at least 6-hours prior to each of the three testing visits. (Otherwise, you may take these medication immediately after pain sensitivity testing has been completed and as prescribed in-between visits)
9. Must experience the symptoms of fibromyalgia syndrome (FMS) that decreases (limits) your ability to perform daily activities.

Exclusions Criteria:

1. You have uncontrolled hypertension(high blood pressure) systolic \>160 mm Hg or diastolic blood pressure \> 100 mm Hg)
2. If you have a history of: heart disease, glaucoma, or hepatitis
3. You have been diagnosed with any type of peripheral neuropathy
4. You have a body mass index (BMI) of more than 34
5. You currently or frequently have thoughts of harming yourself or committing suicide.
6. You are in the process of filing, or plan to file for disability benefits within the study timeline.
7. You plan to undergo an elective surgery within the study timeline.
8. You have been diagnosed with another major rheumatic conditions (i.e. rheumatoid arthritis, systemic lupus erythematosus, scleroderma and other connective tissue diseases)
9. You are currently pregnant, are planning to become pregnant, or are breastfeeding
10. You have been diagnosed with schizophrenia or manic-depressive.
11. You are currently taking any of the following medications:

    1. fluoxetine, Brand Names: Prozac, Prozac Weekly, Rapiflux, Sarafem
    2. sertraline, Brand Name: Zoloft
    3. paroxetine, Brand Names: Paxil, Paxil CR, Pexeva
    4. citalopram, Brand Name: Celexa
    5. escitalopram, Brand Names: Lexapro
    6. venlafaxine, Brand Names: Effexor, Effexor XR
    7. mirtazapine, Brand Names: Remeron, Remeron SolTab
    8. duloxetine, Brand Name: Cymbalta NOTE: If you are taking any of the medication(s) listed above and are willing to discontinue its use for the duration of this study, you must first discuss your decision with your primary care physician (or prescribing doctor)regarding the appropriate regimen to wean off your current medication and receive his/her written consent before proceeding with enrollment. We will provide you a "Dear Doctor" letter that explains the study details.
12. If you are currently taking or have ever taken Savella® (milnacipran)
13. You are currently participating in other pain research study or have previously been enrolled in any study or class in which cognitive behavioral therapy or educational formats were used to help control pain or stress related to fibromyalgia
14. You are unwilling or unable to comply with the study guidelines

Note: If you have ever experienced an adverse event while taking any type of antidepressant, please alert the research team, while it may not exclude you from participating in the study, it is important that we are aware of the incident in order to keep you safe.
C: DISEASE CHARACTERISTICS:

* Patients must be women with histologically confirmed estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive invasive carcinoma of the breast with no evidence of metastatic disease (M0)
* Patients must have completed mastectomy or breast-sparing surgery and must have recovered from all side effects of the surgery
* Patients must have aromatase inhibitor (AI)-associated musculoskeletal symptoms that began or increased after starting AI therapy; new musculoskeletal pain must not be due specifically to fracture or traumatic injury
* Patients must have completed the S1202 Brief Pain Inventory-Short Form (BPI-SF) within 7 days prior to registration; patients must have an "average pain" of at least 4 on the BPI-SF

PATIENT CHARACTERISTICS:

* Patients must be post-menopausal, as defined by at least one of the following:

  * At least 12 months since the last menstrual period
  * Prior bilateral oophorectomy
  * Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND follicle-stimulating hormone (FSH) values consistent with the institutional normal values for the post menopausal state; if patient is under the age of 55, FSH levels must be obtained within 28 days prior to registration OR
  * Have been on LHRH agonist therapy for at least 3 months and estradiol levels drawn within 28 days prior to registration are consistent with the institutional normal values for post-menopausal state.
* Patients must have Zubrod performance status of 0-2
* Patients must have no known allergy or hypersensitivity to duloxetine or any of the inactive ingredients in the matching placebo
* Patients must not have any contraindicated concurrent illnesses listed on the duloxetine package insert including:

  * Current primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history of bipolar disorder, or seizure disorder
  * History of alcohol or other substance abuse or dependence within 365 days prior to registration
  * Chronic liver disease
  * End-stage renal disease
  * Uncontrolled narrow-angle glaucoma
  * Clinically significant coagulation disorder
* Creatinine clearance \> 30 mL/min
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both within 3 x upper limit of normal
* Total bilirubin within the upper limit of normal
* Patients must be able to complete study questionnaires in English or Spanish
* Patients must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis (rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, polymyalgia rheumatica), or cancer involving the bone
* Patients must be willing to submit blood samples for correlative studies; baseline samples must be obtained prior to beginning protocol treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* If patients were treated with chemotherapy and/or radiation therapy, these treatments must be completed at least 28 days prior to study registration
* Concurrent bisphosphonate and trastuzumab therapies are allowed
* Patients should have recovered from all Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the exception of alopecia and peripheral neuropathy
* Patients must currently be taking one of the following aromatase inhibitor (AI) doses for at least 21 days, but no longer than 12 months, prior to registration and plans to continue for at least an additional 180 days after registration

  * Anastrozole (Arimidex®) 1 mg daily
  * Letrozole (Femara®) 2.5 mg daily
  * Exemestane (Aromasin®) 25 mg daily
* Patients must not be taking any contraindicated medications listed on the duloxetine package insert including the following: treatment with phenothiazines, propafenone, flecainide, or linezolid; treatment with monoamine oxidase (MAO)-inhibitor within 14 days prior to registration; or current use of anticoagulation medication (e.g., heparin, warfarin)
* Patients must not require selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephirine reuptake inhibitors (SNRIs), or tricyclic antidepressants during study participation; patients must have been able to taper and discontinue treatment with these medications at least 7 days prior to registration; patients must not have taken duloxetine or milnacipran within 90 days prior to registration
* Patients who are receiving treatment with narcotics, tramadol, gabapentin, and/or pregabalin must have been taking a stable dose for at least 30 days prior to registration
D: Inclusion Criteria:

* Age 21 through 65 years old at registration
* Documentation of delayed gastric emptying on gastric emptying scintigraphy within 2 years of registration, defined as greater than 60% retention at 2 hours or greater than 10% retention at 4 hours
* Symptoms of gastroparesis for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of 21 or greater
* Negative upper endoscopy or upper GI series within 2 years of registration

Exclusion Criteria:

* Normal gastric emptying confirmed with scintigraphy
* Diabetic gastroparesis or post-surgical gastroparesis including fundoplication
* Another active disorder which could explain symptoms in the opinion of the investigator
* History of significant cardiac arrhythmias and/or prolonged QTc
* History of seizures
* Use of narcotics more than 3 days per week
* Use of tricyclic antidepressants for refractory symptoms of gastroparesis within 6 weeks prior to randomization
* Use of strongly anticholinergic medications
* Use of calcium channel blockers
* Use of erythromycin
* Clear history of failed trial of nortriptyline use for gastroparetic symptoms
* Symptoms of primary depression or suicidal ideation
* Contraindications to nortriptyline:

  1. hypersensitivity or allergy to any tricyclic antidepressant drug
  2. concomitant therapy with a monoamine oxidase inhibitor (MAOI)
  3. recent myocardial infarction
  4. glaucoma
* Pregnancy or nursing
* Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study
* Use of a G tube, J tube,or a central catheter for nutrition
* Use of a gastric electrical stimulator
* Failure to give informed consent

Answer: A