Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Duloxetine and Methadone for the Treatment of HIV-Associated Painful Peripheral Neuropathy
Brief Summary: Neuropathy results from damage to the nerves in the feet and legs. It is usually experienced as pain, tingling or numbness. In HIV-infected people, neuropathy can result from the infection itself or be a side effect of antiretroviral treatment. The purpose of this study is to determine whether two different drugs, methadone and duloxetine, reduce neuropathy-associated pain in HIV-infected people. This study will also examine whether utilization of both of these drugs is more effective than treatment with only one.


Options:
A: Inclusion Criteria:

* Major Depressive Disorder according to DSM-IV criteria with at least one previous depressive episode in the patient's medical history
* Painful physical symptoms as measured by the Brief Pain Inventory-Short Form

Exclusion Criteria:

* Any anxiety disorder as a primary diagnosis within the past 6 months (including panic disorder, OCD, PTSD, generalized anxiety disorder and social phobia)
* Any diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders
B: Inclusion Criteria:

* male or female patients
* aged 18 and older who meet criteria for fibromyalgia as defined by the American College of Rheumatology
* have a score of at least 4 on the average pain item of the Brief Pain Inventory (BPI) (modified short form) at visits 1 and 2
* all females must test negative for pregnancy at the time of enrollment
* have a degree of understanding such that the patient can provide informed consent, complete protocol required assessments and communicate intelligibly with the investigator and study coordinator.

Exclusion Criteria:

* have pain symptoms related to traumatic injury, structural rheumatic disease, or regional rheumatic disease that will interfere with interpretation of outcome measures
* have regional pain syndrome, multiple surgeries or failed back syndrome
* have confirmed current or previous diagnosis of rheumatoid arthritis, inflammatory arthritis, or infectious arthritis, or an autoimmune disease (i.e. systemic lupus erythematosus)
C: 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
D: Inclusion Criteria:

* HIV infected
* HIV-associated neuropathy
* Able and willing to provide informed consent
* Successful completion of a daily baseline pain diary over 1 week immediately prior to entry with a mean pain intensity of 4 or more on an 11-point Likert scale
* Karnofsky performance score of 60 or more within 45 days prior to entry
* Required laboratory values. More information on this criterion can be found in the study protocol.
* Willing to comply with protocol requirements for the duration of the study, to include daily completion of the pain diary as instructed, attendance at all study visits, and avoidance of prohibited medications
* On stable or no antiretroviral therapy for 30 days prior to entry. Participants on ARV therapy should plan to remain on the same regimen and drug dose for the duration of the study. Participants not on ARV therapy should have no plans to initiate therapy during study enrollment.
* Not pregnant

Exclusion Criteria:

* Conditions that confound a diagnosis of HIV-associated neuropathy or preclude accurate assessment of neuropathy symptoms, at the discretion of the site investigator. More information on this criterion can be found in the study protocol.
* Potential for unstable neuropathy symptoms during study participation due tthe following: (1) discontinuation of dideoxynucleoside nucleoside reverse transcriptase inhibitor (NRTI) within 16 weeks prior to entry, (2)treatment within 120 days prior to entry with any drug that the site investigator considers may contribute to sensory neuropathy
* Current history of significant depression on antidepressant therapy precluding withdrawal from antidepressants, upon impression of site investigator with input from the participant's mental health provider where available
* History of active substance abuse or dependence identified through medical chart review or self-report such that, in the opinion of the site investigator, participation poses undue risk for the participant
* History of alcohol-related complications within 6 months prior to entry that include but are not restricted to alcohol withdrawal seizures, alcoholic hallucinosis, delirium tremens, or being in an alcohol detoxification program - Treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors (SNRIs), bupropion, or tramadol that, upon judgment of the site investigator, cannot be tapered and discontinued prior to the pre-entry visit
* Treatment with an analgesic opioid regimen of more than 60 mg oral morphine equivalent per day within 45 days prior to entry
* Cognitive impairment that, in the opinion of the site investigator and based on clinical impression, might impact the ability to comply with the study protocol
* Use of an investigational agent within 45 days prior to entry except for expanded-access drugs or drugs used in an ACTG protocol for HIV treatment or for HIV-associated complications, if the drug is not prohibited by this protocol
* Acute active AIDS-defining opportunistic infection (OI) within 30 days prior to entry. Participants with no evidence of active disease and receiving maintenance therapy of AIDS-related OIs will be eligible
* Serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry
* End-stage renal dialysis requiring hemodialysis
* History of known or suspected hepatic cirrhosis diagnosed by signs and symptoms, radiography, or prior liver biopsy with Metavir score of more than 2
* Prolonged QTc interval (more than 0.45 seconds) within 90 days prior to entry
* Felt to be at high risk of opioid-induced respiratory compromise. More information on this criterion can be found in the study protocol.
* Diagnosis of a new seizure disorder or seizure within 90 days prior to entry
* History of acute angle-closure glaucoma, at the discretion of the site investigator
* Known allergy/sensitivity or any hypersensitivity to duloxetine, methadone, acetaminophen, or their ingredients
* Breastfeeding

Answer: D