Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder

NCT ID: NCT00844194

Last Updated: 2014-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28

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.

Conditions

Diabetic Neuropathies; Depressive Disorder, Major

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DPNP with depression (1)

Patients that have diabetic polyneuropathy and depression and are responder to 60 mg duloxetine QD (\>30% pain reduction after week 6)

Group Type: OTHER

Duloxetine 60 mg QD

Intervention Type: DRUG

given to (1) all patients week 2-6; (2) all responders of both arms week 7-12

Duloxetine 30 mg QD

Intervention Type: DRUG

given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks)

DPNP with depression (2)

Patients that have diabetic polyneuropathy and depression and are non-responder to 60 mg duloxetine QD (\<30% pain reduction after week 6)

Group Type: OTHER

Duloxetine 90 mg QD

Intervention Type: DRUG

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

Duloxetine 60 mg QD

Intervention Type: DRUG

given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down

Duloxetine 30 mg QD

Intervention Type: DRUG

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)

Duloxetine 120 mg QD

Intervention Type: DRUG

given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

DPNP without depression (1)

Patients that have diabetic polyneuropathy and no depression and are responder to 60 mg duloxetine QD (\>30% pain reduction after week 6)

Group Type: OTHER

Duloxetine 60 mg QD

Intervention Type: DRUG

given to (1) all patients week 2-6; (2) all responders of both arms week 7-12

Duloxetine 30 mg QD

Intervention Type: DRUG

given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks)

DPNP without depression (2)

Patients that have diabetic polyneuropathy and no depression and are non-responder to 60 mg duloxetine QD (\<30% pain reduction after week 6)

Group Type: OTHER

Duloxetine 90 mg QD

Intervention Type: DRUG

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

Duloxetine 60 mg QD

Intervention Type: DRUG

given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down

Duloxetine 120 mg QD

Intervention Type: DRUG

given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

Duloxetine 30 mg QD

Intervention Type: DRUG

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)

Interventions

Duloxetine 60 mg QD

given to (1) all patients week 2-6; (2) all responders of both arms week 7-12

Intervention Type: DRUG

Duloxetine 60 mg QD

given to (1) all patients week 2-6; (2) all responders of both arms week 7-12

Intervention Type: DRUG

Duloxetine 30 mg QD

given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks)

Intervention Type: DRUG

Duloxetine 30 mg QD

given to (1) all patients for one week as taper in; (2) all patients for taper down (responder for 2 weeks)

Intervention Type: DRUG

Duloxetine 90 mg 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

Intervention Type: DRUG

Duloxetine 90 mg 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

Intervention Type: DRUG

Duloxetine 60 mg QD

given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down

Intervention Type: DRUG

Duloxetine 60 mg QD

given to (1) all patients week 2-6; (2) all non-responders of both arms for first week of taper down

Intervention Type: DRUG

Duloxetine 120 mg QD

given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

Intervention Type: DRUG

Duloxetine 30 mg QD

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 Type: DRUG

Duloxetine 30 mg QD

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 Type: DRUG

Duloxetine 120 mg QD

given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1208.34.49008 Boehringer Ingelheim Investigational Site

Achim Bei Bremen, , Germany

1208.34.49025 Boehringer Ingelheim Investigational Site

Aschaffenburg, , Germany

1208.34.49001 Boehringer Ingelheim Investigational Site

Bad Mergentheim, , Germany

1208.34.49018 Boehringer Ingelheim Investigational Site

Baesweiler, , Germany

1208.34.49002 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1208.34.49005 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1208.34.49009 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1208.34.49021 Boehringer Ingelheim Investigational Site

Bremen, , Germany

1208.34.49028 Boehringer Ingelheim Investigational Site

Frankfurt am Main, , Germany

1208.34.49012 Boehringer Ingelheim Investigational Site

Gera, , Germany

1208.34.49004 Boehringer Ingelheim Investigational Site

Hamburg, , Germany

1208.34.49020 Boehringer Ingelheim Investigational Site

Hamburg, , Germany

1208.34.49023 Boehringer Ingelheim Investigational Site

Hamburg, , Germany

1208.34.49015 Boehringer Ingelheim Investigational Site

Hattingen, , Germany

1208.34.49027 Boehringer Ingelheim Investigational Site

Heidenheim, , Germany

1208.34.49016 Boehringer Ingelheim Investigational Site

Kelkheim, , Germany

1208.34.49006 Boehringer Ingelheim Investigational Site

Limburgerhof, , Germany

1208.34.49022 Boehringer Ingelheim Investigational Site

Münster, , Germany

1208.34.49019 Boehringer Ingelheim Investigational Site

Neuwied, , Germany

1208.34.49024 Boehringer Ingelheim Investigational Site

Saint Ingberg, , Germany

1208.34.49007 Boehringer Ingelheim Investigational Site

Steglitz, , Germany

1208.34.49010 Boehringer Ingelheim Investigational Site

Stuhr, , Germany

1208.34.49013 Boehringer Ingelheim Investigational Site

Unterhaching, , Germany

1208.34.49029 Boehringer Ingelheim Investigational Site

Wiesbaden, , Germany

1208.34.49026 Boehringer Ingelheim Investigational Site

Wuppertal, , Germany

Countries

Germany

Other Identifiers

2008-002731-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1208.34

Identifier Type: -

Identifier Source: org_study_id