Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment of Multi-organ Bodily Distress Syndrome. A Double-blinded Placebo Controlled Trial of the Effects of Imipramine (Stress-3)
Brief Summary: The aim of this study is to test the effect of the tricyclic antidepressant Imipramine in patients with longlasting health problems with no known medical explanation, defined as multi-organ Bodily distress syndrome (BDS). Pharmacological treatment of patients with BDS have never been tested, and Imipramine i low dosage (10-75 mg) has the potential of reducing both pain and other symptoms of bodily distress for patients with BDS. Control conditions are pill placebo. Study duration is 19 weeks for each of the 140 patients. End point is 13 weeks, i.e. after 10 weeks of 25-75 mg study drug.


Options:
A: 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
B: Inclusion Criteria:

1. First time refered patients fulfilling diagnostic criteria for BDS multi-organ type with symptoms for more than 3 of 4 symptom categories
2. Moderate or severe impact on daily life
3. Symptoms lasting for at least 2 years
4. Age 20-50 years
5. Born in Denmark or have Danish parents. The patient understands, speaks, writes and read Danish.

Exclusion Criteria:

1. Presence og other physical of psychiatric condition, if the symptoms of this condition can not clearly be separated from symptoms of BDS
2. Current moderate or severe depression, patients in continuous antidepressant treatment because of moderate or severe depression, and patients with other severe psychiatric disorder that demands treatment, or if the patient is suicidal.
3. A lifetime-diagnosis of psychoses, mania or depression with psychotic symptoms (ICD-10: F20-29, F30-31, F32.3, F33.3)
4. Abuse of alcohol, narcotics or drugs
5. Pregnancy, breastfeeding or current pregnancy wish. Fertile women must use effective anticonception, (hormonal contraception, contraceptive injection, implant or patches, intrauterine system and device, vaginal ring).
6. Treatment with all pain modulating drugs, e.g. all analgesics, antidepressants, antiepileptica and other types of medication with pain relieving properties must be discontinued at least two weeks before the treatment phase.
7. Imipramine treatment in sufficient dosage within the last year, i.e. 25 mg daily continuously for at least 8 weeks.
8. Allergy to study medication or excipients in study medication.
9. Patients with previous med myocardial infarction, congestive heart failure, signs of conduction defects or abnormalities on ECG (first degree AV-block, bundle branch block or prolonged QT-interval), narrow-angle glaucoma, porphyria, inherited galactose intolerance, epilepsy, hepatic insufficiency and severe renal impairment
10. Simultaneous use of:

    * antipsychotics
    * oral anticoagulants
    * diuretics
    * sympathomimetics and CNS-stimulating drugs (amphetamine-like drugs)
    * all serotonergic drugs, e.g. SSRI, SNRI and TCA, the dietary supplement hypericum perforatum, non-selective, irreversible or selective, reversible monoamine oxidase (MAO) inhibitors, triptans, tramadol, pethidin and tryptophan
    * the drugs cimetidine (H2-antagonist), quinidine (antiarrythmics), clonidine (antihypertensive), fluconazol (antimycotics), clindamycin, clarithromycin, erythromycin (antibiotics), droperidol (anaesthetic), levodopa (antiparkinson), mefloquine (antimalaria), phenytoin, barbiturates, carbamazepin (antiepileptica)
    * Bupropion (tobacco dependence), celecoxib (NSAID), cinacalcet (antiparathyroid drug), duloxetine (SNRI), flufenazin (antipsychotic), fluoxetin (SSRI), gefitinib (antineoplastic), moclobemid (MAO), paroxetine, Sertraline (SSRI), Terbinafine (antimycotics), Yohimbin (erectile dysfunction) samt fluvoxamin (SSRI), ciprofloxacin and enoxacin (microbiotic), because plasma concentration of Imipramine can increase with the simultaneous use of these potent CYP2D6- and CYP1A2- inhibitors
C: Inclusion Criteria:

* Participants with present OA.
* Have pain for ≥ 14 days of each month for 3 months prior to study entry.
* Participants must have a score of ≥4 on the BPI average pain score before randomization.
* Females of child-bearing potential must test negative (-) on a pregnancy test.

Exclusion Criteria:

* Participants who cannot appropriately complete the daily diaries.
* Have a score change of ≧3 on BPI 24-hour average pain score between screening and baseline.
* Participants who have serious cardiovascular, hepatic, renal, endocrine, respiratory, or hematologic illness, peripheral vascular disease, or other medical condition or neuropsychiatric conditions or clinically significant laboratory abnormalities or electrocardiographic abnormalities.
* Participants who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) higher than 100 international units per liter (IU/L) or total bilirubin higher than 1.6 milligrams/deciliter (mg/dL).
* Participants who have serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or are receiving renal dialysis.
* Participants who have a diagnosis of inflammatory arthritis (that is, rheumatoid arthritis) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis and Type 1 diabetes).
* Participants who have any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
* Participants who have major depressive disorder as determined using depression module of the Mini-International Neuropsychiatric Interview (M.I.N.I.).
* Participants who have uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension.
* Participants who have received intrarticular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 1 month.
* Participants who have had knee arthroscopy of the index knee within the past year or joint replacement of the index knee or osteotomy at anytime.
* Participants who have end-stage osteoarthritis or surgery planned during the trial for the index joint.
* Participants have a prior synovial fluid analysis showing a white blood cell (WBC) ≥2000 cubic millimeters (mm3) that is indicative of a diagnosis other than OA.
* Participants taking any excluded medications that cannot be discontinued.
* Participants anticipated by the investigator to require use of nonsteroidal anti-inflammatory drugs that include acetaminophen, opioid analgesics, or other excluded medication for the duration of the study.
* Participants treated with a monoamine oxidase inhibitor (MAoI) within 14 days prior to baseline, or those with the potential need to use MAO inhibitor during the study or within 5 days of discontinuation of investigational drug.
* Participants who answer 'yes' to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia-Suicide Severity Rating Scale, suicide ideation section-questions 4 and 5; suicidal behaviors section).
* Participants who have a history of having more than one medical allergy.
* Are non-ambulatory or require the use of crutches or a walker.
* Have frequent falls that could result in hospitalization or could compromise response to treatment.
* Have a primary painful condition that may interfere with assessment of the index joint, i.e., knee.
* Have a history of drug abuse or dependence within the past year, including alcohol and excluding nicotine and caffeine.
* Have a positive urine drug screen for any substances of abuse or excluded medication.
* Have received administration of another investigational drug within the 30 days prior to screening.
* Have had previous exposure to duloxetine or completed/withdrawn from any study investigating duloxetine.
* Pregnant participants, female participants who wish to be pregnant during the clinical study period, or participants who are breast-feeding; or male participants who wish pregnancy of the partner.
D: 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.

Answer: B