Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder
Condition: Diabetic Neuropathies; Depressive Disorder, Major
MeSH terms: Neuralgia; Diabetic Neuropathies; Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Duloxetine 60 mg QD; Duloxetine 60 mg QD; Duloxetine 30 mg QD; Duloxetine 30 mg QD; Duloxetine 90 mg QD; Duloxetine 90 mg QD; Duloxetine 60 mg QD; Duloxetine 60 mg QD; Duloxetine 120 mg QD; Duloxetine 30 mg QD; Duloxetine 30 mg QD; Duloxetine 120 mg QD
Intervention description: given to (1) all patients week 2-6; (2) all responders of both arms week 7-12; given to (1) all patients week 2-6; (2) all responders of both arms week 7-12; given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks); given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks); given to non-responders of both arms from day of notice that 120 mg is not tolerated to week 12 as 60 mg+30 mg Duloxetine QD; given to non-responders of both arms from day of notice that 120 mg is not tolerated to week 12 as 60 mg+30 mg Duloxetine QD; given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down; given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down; given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated; given to (1) all patients for one week as taper in; (2) all patients for taper down (non-responder for the second week of taper down); given to (1) all patients for one week as taper in; (2) all patients for taper down (non-responder for the second week of taper down); given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective is to evaluate, separately in diabetic polyneuropathic pain (DPNP)
      patients with and without co-morbid major depressive disorder (MDD), whether duloxetine given
      as 60 mg to 120 mg once daily (QD) leads to a clinically relevant improvement as measured by
      the change in Brief Pain Inventory (BPI) 24 hours average interference score from baseline to
      after 12 weeks. A clinically relevant improvement will be demonstrated if the confidence
      interval for the mean change from baseline does not lie above the clinically relevant change
      of -1.35. If statistically significant results are obtained for the DPNP patients with MDD,
      then the same evaluation will be performed for the DPNP patients without MDD in another
      confirmatory analysis.

      As secondary objectives the study will compare the two groups (MDD+/MDD-) regarding efficacy
      of duloxetine on BPI severity scales, the distribution of different percentages of pain
      reduction among the patient population, and the patients and physicians impressions of
      severity and improvement of pain.

      The study will also compare treatment outcomes regarding patient-relevant functionality and
      quality of life (QoL) between the two groups (MDD+/MDD-) by evaluating each single BPI
      interference item, the Short Form 12 (SF-12) Health Questionnaire and the West Haven
      Multidimensional Pain Inventory (MPI).

      As a third group of secondary objectives the efficacy of duloxetine of the psychological
      symptoms (e.g. depression) of DPNP patients with or without depression will be assessed using
      the Hamilton depression scale, the Beck Depression Inventory-II and the hospital Anxiety and
      Depression Scale.

      Further the effect of duloxetine treatment on fasting blood glucose (FBG) and hemoglobin A1c
      (HbA1c) will be evaluated.

      To monitor safety and tolerability, treatment discontinuation rates, treatment emergent
      adverse events, change in vital signs, laboratory results and suicidal thoughts will be
      assessed.
    

Eligibility criteria:

        Inclusion criteria:

          1. Present with pain due to bilateral peripheral neuropathy (according to International
             Statistical Classification of Diseases and Related Health Problems 10 (ICD 10).

          2. To qualify for the MDD+ cohort, patients need to meet the ICD-10 criteria for MDD.
             Furthermore, Hamilton rating scale for depression 17 (HAMD-17) scores need to match
             with the ICD-10 criteria for qualification of the MDD+ or MDD- groups.

          3. Male or female outpatients at least 18 years of age.

          4. Females with child bearing potential must test negative for a serum pregnancy test at
             Visit 1. Females of child-bearing potential (not surgically sterilized and between
             menarche and 1 year post-menopause) must agree to utilize medically acceptable and
             reliable means of birth control as determined by the investigator during the study and
             for 1 month following the last dose of the study. Examples of reliable methods include
             use of oral contraceptives or Depo-Clinovir Contraceptive Injection (sterile
             medroxyprogesterone acetate suspension, Pharmacia), partner with vasectomy, diaphragms
             with contraceptive jelly, cervical caps with contraceptive jelly, condoms with
             contraceptive foam, or intrauterine devices. Women who are pregnant or breast-feeding
             may not participate in the study.

          5. Educational level and degree of understanding such that they can communicate
             intelligibly with the investigator and study coordinator.

          6. Judged to be reliable and agrees to keep all appointments for clinic visits, tests,
             and procedures required by the protocol.

        Exclusion criteria:

          1. Have already a diagnosis of Depression and are currently treated with an
             antidepressant medication for depression, when entering the study.

          2. Suffer from pain that cannot be clearly differentiated from or conditions that
             interfere with the assessment of DPNPain.

          3. Had a historical exposure to drugs known to cause neuropathy, that could have been
             responsible for neuropathy.

          4. Have previously been treated with duloxetine (for DPNP or MDD)

          5. Are judged to be at suicidal risk by the clinical investigator or as defined by a
             score of 2 or greater on question 9 of the Beck Depression Inventory-II (BDI-II).

          6. Had a history of substance abuse or dependence within the past year, excluding
             nicotine and caffeine.