Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of Milnacipran or Placebo on Ventricular Lactate Levels and Fibromyalgia Induced "Brain Fog."
Brief Summary: Use of the drug Milnacipran will reduce ventricular lactate levels and processing time for completing complex tasks relative to placebo.


Options:
A: Inclusion Criteria:

* Female or male subjects who fulfill the American College of Rheumatology's case definition for Fibromyalgia.
* 18 through 68 years of age

Exclusion Criteria:

* Pregnant or trying to become pregnant
* Taking any other Serotonin Norepinephrine Reuptake Inhibitor (SNRI) or already taking milnacipran
* Patients who do not indicate their pain levels as less than substantial despite their best care
* History of any psychotic disorder or history of alcoholism or drug abuse within 10 years of intake as determined by psychiatric diagnostic interview
* Presence of current depression as determined by psychiatric diagnostic interview
* Presence of brain lesion on MRI anatomical study
B: Inclusion Criteria:

1. 18 years of age or above
2. Have a diagnosis of Diabetes mellitus for at least a year
3. Agree not to smoke whilst resident in the CRC
4. Able to understand the patient information sheet and provide written informed consent
5. Score above 12 on the LANSS
6. Have neuropathic pain of diabetic origin
7. Score above 25 on MMSE
8. Willing to withdraw, under the guidance of their diabetologist, from any current pain medication prior to their first visit to the sleep laboratory. Duration of withdrawal will be at least equivalent to 5 half-lives and will be of a relevant duration given the particular medication used.

Exclusion Criteria:

1. There is evidence of an end stage disease of a major system (hepatic, renal, respiratory, haematologic (PA), immunologic, cardiovascular, inflammatory, rheumatology, active infections, peripheral vascular disease, untreated endocrine(hypothyroid)
2. There is evidence of a recent ischaemic event
3. There is evidence of recurrent and/or severe hypoglycemia requiring assistance in last 3 years
4. Evidence of sleep pathology that would interfere with the assessment of treatment (assessed on habituation night)
5. Currently receiving treatment for malignancy
6. Suffer from seizures including epilepsy
7. There is evidence of a history of dependence on or abuse of alcohol/recreational drugs
8. Need to use a wheel chair (incompatible with studies in a sleep laboratory)
9. Involved in a clinical trial in last 3 months
10. Pregnant, lactating or inadequate contraception
11. Vision inadequate for the performance tests (as assessed at screening)
12. Colour Blind
13. Will not co-operate with study procedures
14. Will not give permission to inform GP
C: 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
D: 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

Answer: A