Please select the eligibility criteria that correspond to the clinical trial below.
Title: An 8-Week, Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study of [S,S]-Reboxetine Administered Once Daily in Patients With Fibromyalgia
Brief Summary: The purpose of this study is to assess the safety and effectiveness of \[S,S\]-Reboxetine in patients with fibromyalgia.


Options:
A: 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
B: Inclusion Criteria:

* Confirmed diagnosis of SPMS. Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Evidence of progression, either an increase of at least one point in EDSS or clinical documentation of increasing disability in patient notes
* Expanded Disability Status Scale (EDSS) 4.0-6.5
* Aged 25 to 65 inclusive
* Women and men with partners of childbearing potential must be using an appropriate method of contraception to avoid any unlikely teratogenic effects of the 3 drugs from time of consent, to 6 weeks after treatment inclusive
* Women must have a negative pregnancy test within 7 days prior to the baseline visit unless not of child bearing potential (e.g. have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy or they are postmenopausal)
* Willing and able to comply with the trial protocol (e.g. can tolerate MRI and fulfils the requirements for MRI, e.g. not fitted with pacemakers or permanent hearing aids), ability to understand and complete questionnaires
* Written informed consent provided

Exclusion Criteria:

* Pregnancy or breast feeding patients
* Baseline MRI scan not of adequate quality for analysis (e.g. too much movement artefact)
* Significant organ co-morbidity (e.g. malignancy or renal or hepatic failure)
* Relapse within 3 months of baseline visit
* Patients who have been treated with iv or oral steroids for an MS relapse/progression within 3 months of baseline visit (these patients can undergo future screening visits once the 3 month window has expired), patients on steroids for another medical condition may enter as long as the steroid prescription is not for multiple sclerosis (relapse/ progression).
* Use of Simvastatin at 80mg dose within 3 months of baseline visit (lower doses of Simvastatin and other statins are permissible)
* Commencement of fampridine within 6 months of baseline visit
* Use of immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) or disease modifying treatments (β-interferons, glatiramer) within 6 months of baseline visit
* Use of fingolimod/fumarate/teriflunomide/laquinomod/or other experimental disease modifying treatment (including research of an investigational medicinal product) within 12 months of baseline visit
* Use of mitoxantrone/ natalizumab/ alemtuzumab/ daclizumab if treated within 12 months of baseline visit
* Primary progressive MS
* Relapsing-remitting MS
* Known hypersensitivity to the active substances and their excipients to any of the active drugs for this trial
* Use of: lithium, chlorpropamide, triamterene and spironolactone within 6 months of the baseline visit
* Current use of potassium supplements
* Current use of tamoxifen
* Current use of herbal treatments containing St. John's Wort
* Significant signs of depression
* Use of an SSRI within 6 months of the baseline visit
* Use of monoamine oxidase inhibitors, phenytoin, L-tryptophan) and/or neuroleptic drugs within 6 months of the baseline visit
* A Beck Depression Index score of 19 or higher
* Bipolar disorder
* Receiving or previously received Electro-Convulsive Therapy
* Epilepsy/seizures
* Glaucoma
* Patients with a history of bleeding disorders or currently on anticoagulants Routine screening blood values (LFT) \>/ 3 x upper limit of normal (ULN) of site reference ranges (ALT/AST, bilirubin,ˠGT) Potassium \<2.8mmol/l or \>5.5mmol/l
* Sodium \<125mmol/l
* Creatinine \>130μmol/l
* WBCs \<3 x 109/l
* Lymphocytes \<0.8 x 109/l
* Neutrophil count \<1.0 x 109 /l
* Platelet count \<90 x 109 /l
* Haemoglobin \<80g/l
C: Inclusion Criteria:

* Radiographically defined OA knee changes with knee pain
* Must have self-reported knee pain
* Able to give informed consent
* Over 35 years old
* Male or female
* Females not pregnant or lactating and using effective contraception

Exclusion Criteria:

* People with any known contraindication to MRI like

  * Intraocular metallic foreign bodies;
  * Intracranial aneurysm clips;
  * Cardiac pacemakers and defibrillators;
  * Cochlear implants;
* People with a significant head tremor;
* People with potential metal foreign bodies due to previous accidents;
* Breastfeeding or pregnancy, confirmed by pregnancy test;
* People that are felt to be unfit for the MRI scan according to the judgement of medically qualified personnel, either on the research team, or the patient's clinical team. (eg. due to back pain, claustrophobia, acute sickness etc.) This includes patients with signs of impaired temperature regulation such as an extremely high fever;
* Patients with large tattoos, specifically in the head, neck or shoulder region;
* Persons that do not have the capacity to consent;
* Aged less than 35;
* Major medical, neurological and psychiatric co-morbidities;
* Other significant medical condition;
* Metallic agents embedded within the body (ie. Shrapnel, surgical pins);
* Refusal by participant to general practitioner (GP) being informed;
* Have uncontrolled narrow-angle glaucoma;
* Have recently taken monoamine oxidase inhibitor (MAOI) or Mellaril® (thioridazine);
* Taking fluvoxamine, ciprofloxacin or enoxacin;
* Taking St. John's Wort, a herbal treatment (Hypericum perforatum);
* Taking other medicines containing duloxetine;
* Have liver disease or severe kidney disease;
* Currently on antidepressant treatment, including treatment for pain with tricyclic agents such as amitryptiline;
* Have recently taken monoamine oxidase inhibitor (MAOI) or Mellaril® (thioridazine);
* Taking tramadol;
* Known hypersensitivity, allergy or intolerance to one of duloxetine's components;
* Unwillingness to take caution in relation to use of other centrally active substances such as alcohol and sedative drugs;
* Current treatment with potent inhibitors of CYP1A2 like fluvoxamine;

Participants undergoing acute treatment (remifentanil or placebo) have, in addition to the stated above, the following exclusion criteria:

* Taking morphine
* Known hypersensitivity, allergy or intolerance to one of remifentanil's components or other fentanyl - analogues
* Current treatment with cardiac depressant drugs such as beta-blockers and calcium channel blocking agents
D: Inclusion Criteria:

* At screening patients must meet the ACR criteria for fibromyalgia (i.e. widespread pain for at least 3 months, and pain in at least 11 of 18 specific tender point sites).
* At screening and randomization, patients must have a score of \>/=40mm on the Visual Analog Scale (VAS) of the Short-Form-McGill Pain Questionnaire (SF-MPQ).

Exclusion Criteria:

* Patients with other severe pain (e.g. DPN and PHN) that may confound assessment or self-evaluation of the pain associated with fibromyalgia.
* Patients with severe hepatic impairment.

Answer: D