Clinical trial NCT00457730 (phase 2/phase 3, status: completed)
Conditions: multiple sclerosis
ICD codes: G35, C81.18
Drugs: duloxetine, placebo
SMILES: CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of MS made at least 3 months prior based on McDonald or Proser criteria.

          -  Age over 17.

          -  Clinical stability defined as no MS exacerbation or change in disease modifying
             therapy for 90 days prior to screening.

          -  Daily pain attributed to MS, present for a minimum of 2 months prior to screening.

          -  Minimum baseline score of 4 on the 24-h Worst Pain Score rated on an 11 point (0-10)
             point Likert Scale within the identified region of central pain.

        Exclusion Criteria:

          -  Pain that could not clearly be differentiated from causes other than Multiple
             Sclerosis, such as diabetic neuropathy, PVD, arthritis or other musculoskeletal
             condition, chronic headache, visceral pain.

          -  Transient pains such as dysesthetic L'Hermittes sign alone.

          -  Current or historical diagnosis of mania, bipolar disorder or psychosis.

          -  Concomitant use of monoamine oxidase inhibitors (MAOI) or thioridazine.(MAOI drug must
             be discontinued 14 days prior to enrollment. At least 5 days must have passed after
             study drug discontinuation before MAOI drug may be started.)

          -  Concomitant use of a serotonin reuptake inhibitor or venlafaxine or duloxetine within
             4 weeks of baseline.

          -  Use of any analgesic medication except ibuprofen for neurogenic pain 7 days prior to
             the baseline visit and until study termination.

          -  Use of an opioid, marijuana or dronabinol within 7 days of baseline.

          -  Narrow angle glaucoma.

          -  Depression with suicidality.

          -  Substantial alcohol use. Because it is possible that Duloxetine and alcohol interact
             to cause liver injury, duloxetine should not be prescribed to patients with
             substantial alcohol use. Potential subjects will be asked how much alcohol they drink.
             If the answer is over 2 drinks a day this will generally constitute an exclusion.

          -  History of chronic hepatic insufficiency or ALT or AST> twice the upper limit of
             normal. Because it is possible thast Duloxetine may aggravate pre exisitng liver
             disease, duloxetine should not be prescribed to patients with chronic liver disease.

          -  Renal insufficiency (Creatinine Clearance , 30mL/minor serum creatinine > 1.9).
             Duloxetine is not recommended for patients with end stage renal disease (requiring
             dialysis) or severe renal impairment. Population PK analyses suggest that mild to
             moderate degrees of renal dysfunction (estimated CrCl 30-80ml/min)have no significant
             effect on Duloxetine clearance. We will calculate creatinine clearance using the
             Cockcroft-Gault calculation. This is the most common calculation used in FDA producy
             labeling: Males=(140-age)(wt in kg)(serum creatinine)(72). Females= malesx 0.85.

          -  Uncontrolled hypertention (SBP>180, DBP>105)

          -  Females who are breast feeding, pregnant, or have potential to become pregnant during
             the course of the study.(fertile and unwilling/unable to use effective contraceptive
             measures)

          -  Any other serious and/or unstable medical condition.

          -  Allergy to ibuprofen or any other non steroidal anti inflammatory drug (NSAID)

          -  Any history of peptic ulcer disease within 2 years or lifetime history of
             NSAID-associated gastritis or other toxicity.

          -  Patients taking low dose aspirin will be instructed to contact their primary
             physicianto ask whether they may safely discontinue aspirin while participating in
             this study. If the recommendation is to continue aspirin or if use of aspirin is for
             secondary prevention of arteriosclerotic disease, then they will be excluded.