Clinical trial NCT00844194: Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder
Official title: A 12 Weeks Open Label Two Parallel Groups Study to Assess the Efficacy of Orally Administered Duloxetine 60 mg and 120 mg Per Day on Treatment Outcomes in Patients With Diabetic Peripheral Neuropathic Pain With and Without Co-morbid Major Depressive Disorder. The Primary Objective of This Study is to Evaluate Whether the Efficacy of Duloxetine Given as 60 mg to 120 mg Once Daily (QD), Measured by the BPI Interference Score After 12 Weeks Shows a Clinically Relevant Improvement in the DPNP Patients With Co-morbid MDD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Neuropathies
Depressive Disorder, Major
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-02-16
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in BPI Worst Pain During Treatment From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Worst Pain (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Worst Pain (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Least Pain (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Least Pain During Treatment (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Least Pain (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Average Pain (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Average Pain During Treatment (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Average Pain (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Number of Patients With a Reduction in BPI Average Pain at Week 2
timeFrame: Baseline and Week 2
measure: Number of Patients With a Reduction in BPI Average Pain at Week 6
timeFrame: Baseline and Week 6
measure: Number of Patients With a Reduction in BPI Average Pain at Week 12
timeFrame: Baseline and Week 12
measure: Change in Pain During Treatment (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Pain (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Pain During Treatment (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 2
timeFrame: Baseline and Week 2
measure: Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 6
timeFrame: Baseline and Week 6
measure: Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With General Activity (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With General Activity (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With General Activity (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Mood (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Mood (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Mood (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Sleep (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Sleep (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Sleep (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Patient Global Impression - Improvement (PGI-I) at Week 2
timeFrame: Baseline and Week 2
measure: Patient Global Impression - Improvement (PGI-I) at Week 6
timeFrame: Baseline and Week 6
measure: Patient Global Impression - Improvement (PGI-I) at Week 12
timeFrame: Baseline and Week 12
measure: Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Total Score From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in HADS Anxiety Total Score From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in HADS Anxiety Total Score From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in HADS Depression Total Score From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in HADS Depression Total Score From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in HADS Depression Total Score From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Interference of Pain (With Subjective Well-being) From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Interference of Pain From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Support From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Support Which the Patient Received From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Degree to Which Significant Others Display Distracting Responses to the Patient's Pain Behaviors and Complaints From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Degree to Which Significant Others Display Distracting Responses to the Patient's Pain Behaviors and Complaints From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Clinical Global Impression - Severity Pain From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Clinical Global Impression - Severity Pain From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Clinical Global Impression - Severity Pain From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Hamilton Depression Score From Baseline to Week 2
timeFrame: Baseline and Week 2
measure: Change in Hamilton Depression Score From Baseline to Week 6
timeFrame: Baseline and Week 6
measure: Change in Hamilton Depression Score From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Suicidal Thoughts by BDI-II at Week 2
timeFrame: Week 2
measure: Suicidal Thoughts by BDI-II at Week 6
timeFrame: Week 6
measure: Suicidal Thoughts by BDI-II at Week 12
timeFrame: Week 12
measure: Suicidal Thoughts or Behaviours by HAMD-17 at Week 2
timeFrame: Week 2
measure: Suicidal Thoughts or Behaviours by HAMD-17 at Week 6
timeFrame: Week 6
measure: Suicidal Thoughts or Behaviours by HAMD-17 at Week 12
timeFrame: Week 12
measure: Change of Fasting Blood Glucose From Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Change of Systolic Blood Pressure From Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Change of Diastolic Blood Pressure From Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Change of Pulse Rate From Baseline at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Achim bei Bremen
country: Germany
facility: 1208.34.49008 Boehringer Ingelheim Investigational Site
city: Aschaffenburg
country: Germany
facility: 1208.34.49025 Boehringer Ingelheim Investigational Site
city: Bad Mergentheim
country: Germany
facility: 1208.34.49001 Boehringer Ingelheim Investigational Site
city: Baesweiler
country: Germany
facility: 1208.34.49018 Boehringer Ingelheim Investigational Site
city: Berlin-Steglitz
country: Germany
facility: 1208.34.49007 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1208.34.49002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1208.34.49005 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1208.34.49009 Boehringer Ingelheim Investigational Site
city: Bremen
country: Germany
facility: 1208.34.49021 Boehringer Ingelheim Investigational Site
city: Frankfurt am Main
country: Germany
facility: 1208.34.49028 Boehringer Ingelheim Investigational Site
city: Gera
country: Germany
facility: 1208.34.49012 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1208.34.49004 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1208.34.49020 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1208.34.49023 Boehringer Ingelheim Investigational Site
city: Hattingen
country: Germany
facility: 1208.34.49015 Boehringer Ingelheim Investigational Site
city: Heidenheim
country: Germany
facility: 1208.34.49027 Boehringer Ingelheim Investigational Site
city: Kelkheim
country: Germany
facility: 1208.34.49016 Boehringer Ingelheim Investigational Site
city: Limburgerhof
country: Germany
facility: 1208.34.49006 Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: 1208.34.49022 Boehringer Ingelheim Investigational Site
city: Neuwied
country: Germany
facility: 1208.34.49019 Boehringer Ingelheim Investigational Site
city: St. Ingberg
country: Germany
facility: 1208.34.49024 Boehringer Ingelheim Investigational Site
city: Stuhr
country: Germany
facility: 1208.34.49010 Boehringer Ingelheim Investigational Site
city: Unterhaching
country: Germany
facility: 1208.34.49013 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1208.34.49029 Boehringer Ingelheim Investigational Site
city: Wuppertal
country: Germany
facility: 1208.34.49026 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: