Conditions: Diabetic Neuropathies Depressive Disorder, Major
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 108
Healthy volunteers: no

Brief 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.

Detailed description:

Arms:
arm 1: Patients that have diabetic polyneuropathy and depression and are responder to 60 mg duloxetine QD (\>30% pain reduction after week 6) arm 2: Patients that have diabetic polyneuropathy and depression and are non-responder to 60 mg duloxetine QD (\<30% pain reduction after week 6) arm 3: Patients that have diabetic polyneuropathy and no depression and are responder to 60 mg duloxetine QD (\>30% pain reduction after week 6) arm 4: Patients that have diabetic polyneuropathy and no depression and are non-responder to 60 mg duloxetine QD (\<30% pain reduction after week 6)

Interventions: intervention 1: Duloxetine 60 mg QD intervention 2: Duloxetine 60 mg QD intervention 3: Duloxetine 30 mg QD intervention 4: Duloxetine 30 mg QD intervention 5: Duloxetine 90 mg QD intervention 6: Duloxetine 90 mg QD intervention 7: Duloxetine 60 mg QD intervention 8: Duloxetine 60 mg QD intervention 9: Duloxetine 120 mg QD intervention 10: Duloxetine 30 mg QD intervention 11: Duloxetine 30 mg QD intervention 12: Duloxetine 120 mg QD
Intervention descriptions: intervention 1: given to (1) all patients week 2-6; (2) all responders of both arms week 7-12 intervention 2: given to (1) all patients week 2-6; (2) all responders of both arms week 7-12 intervention 3: given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks) intervention 4: given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks) intervention 5: 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 intervention 6: 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 intervention 7: given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down intervention 8: given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down intervention 9: given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated intervention 10: 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) intervention 11: 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) intervention 12: given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

Protocol document: