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

Depressive Disorder, Major Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844194
• Other study ID #: 1208.34
• Secondary ID: 2008-002731-32
• Status: Completed
• Phase: Phase 4
• First received: February 13, 2009
• Last updated: May 2, 2014
• Start date: February 2009

Study information

• Verified date: December 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Diabetic Neuropathies
• Neuralgia

Intervention

Drug:
• Duloxetine 60 mg QD
given to (1) all patients week 2-6; (2) all responders of both arms week 7-12
• Duloxetine 60 mg QD
given to (1) all patients week 2-6; (2) all responders of both arms week 7-12
• 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)
• 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)
• 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
• 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
• 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
• 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
• Duloxetine 120 mg QD
given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated
• 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)
• 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)
• Duloxetine 120 mg QD
given to non-responders of both arms from week 7-12 as 2x60 mg Duloxetine QD, if tolerated

Locations

Country	Name	City	State
Germany	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	1208.34.49007 Boehringer Ingelheim Investigational Site	Berlin-Steglitz
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	St. Ingberg
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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI average interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI average interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in BPI Worst Pain During Treatment From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 2	No
Secondary	Change in Worst Pain (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 6	No
Secondary	Change in Worst Pain (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 12	No
Secondary	Change in Least Pain (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 2	No
Secondary	Change in Least Pain During Treatment (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 6	No
Secondary	Change in Least Pain (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 12	No
Secondary	Change in Average Pain (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 2	No
Secondary	Change in Average Pain During Treatment (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 6	No
Secondary	Change in Average Pain (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 12	No
Secondary	Number of Patients With a Reduction in BPI Average Pain at Week 2		Baseline and Week 2	No
Secondary	Number of Patients With a Reduction in BPI Average Pain at Week 6		Baseline and Week 6	No
Secondary	Number of Patients With a Reduction in BPI Average Pain at Week 12		Baseline and Week 12	No
Secondary	Change in Pain During Treatment (BPI) From Baseline to Week 2	The change from baseline reflects the pain at week 2 minus the pain at baseline. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 2	No
Secondary	Change in Pain (BPI) From Baseline to Week 6	The change from baseline reflects the pain at week 6 minus the pain at baseline. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 6	No
Secondary	Change in Pain During Treatment (BPI) From Baseline to Week 12	The change from baseline reflects the pain at week 12 minus the pain at baseline. The BPI pain ranges from 0 (no pain) to 10 (pain as bad as the patient can imagine).	Baseline and Week 12	No
Secondary	Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 2	The change from baseline reflects the week 2 value minus the baseline value. The relief of pain ranges from 0% (no relief) to 100% (complete relief).	Baseline and Week 2	No
Secondary	Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 6	The change from baseline reflects the week 6 value minus the baseline value. The relief of pain ranges from 0% (no relief) to 100% (complete relief).	Baseline and Week 6	No
Secondary	Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 12	The change from baseline reflects the week 12 value minus the baseline value. The relief of pain ranges from 0% (no relief) to 100% (complete relief).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With General Activity (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With General Activity (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With General Activity (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Mood (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Mood (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Mood (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Sleep (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Sleep (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Sleep (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 2	No
Secondary	Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 6	No
Secondary	Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BPI interference score ranges from 0 (pain does not interfere) to 10 (pain completely interferes).	Baseline and Week 12	No
Secondary	Patient Global Impression - Improvement (PGI-I) at Week 2	The investigator judged the improvement of the patient's global impression during treatment. The score ranges from 1 (very much better) to 7 (very much worse).	Baseline and Week 2	No
Secondary	Patient Global Impression - Improvement (PGI-I) at Week 6	The investigator judged the improvement of the patient's global impression during treatment. The score ranges from 1 (very much better) to 7 (very much worse).	Baseline and Week 6	No
Secondary	Patient Global Impression - Improvement (PGI-I) at Week 12	The investigator judged the improvement of the patient's global impression during treatment. The score ranges from 1 (very much better) to 7 (very much worse).	Baseline and Week 12	No
Secondary	Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The BDI-II total score ranges from 0 to 63, with a higher score indicating a higher level of depression.	Baseline and Week 2	No
Secondary	Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The BDI-II total score ranges from 0 to 63, with a higher score indicating a higher level of depression.	Baseline and Week 6	No
Secondary	Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The BDI-II total score ranges from 0 to 63, with a higher score indicating a higher level of depression.	Baseline and Week 12	No
Secondary	Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Total Score From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The HADS anxiety total score ranges from 0 (no anxiety) to 21 (extreme anxiety).	Baseline and Week 2	No
Secondary	Change in HADS Anxiety Total Score From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The HADS anxiety total score ranges from 0 (no anxiety) to 21 (extreme anxiety).	Baseline and Week 6	No
Secondary	Change in HADS Anxiety Total Score From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The HADS anxiety total score ranges from 0 (no anxiety) to 21 (extreme anxiety).	Baseline and Week 12	No
Secondary	Change in HADS Depression Total Score From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The HADS depression total score ranges from 0 (no depression) to 21 (extreme depression).	Baseline and Week 2	No
Secondary	Change in HADS Depression Total Score From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The HADS depression total score ranges from 0 (no depression) to 21 (extreme depression).	Baseline and Week 6	No
Secondary	Change in HADS Depression Total Score From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The HADS depression total score ranges from 0 (no depression) to 21 (extreme depression).	Baseline and Week 12	No
Secondary	Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. A lower score corresponds to a lower level of physical health. Values can range from 0 to 100.	Baseline and Week 6	No
Secondary	Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. A lower score corresponds to a lower level of physical health. Values can range from 0 to 100.	Baseline and Week 12	No
Secondary	Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. A lower score corresponds to a lower level of mental health. Values can range from 0 to 100.	Baseline and Week 6	No
Secondary	Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. A lower score corresponds to a lower level of mental health. Values can range from 0 to 100.	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Interference of Pain (With Subjective Well-being) From Baseline to Week 6	Pain-related life interference (with family and marital functioning, work, social activities). The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (no interference) to 6 (extreme interference).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Interference of Pain From Baseline to Week 12	Pain-related life interference (with family and marital functioning, work, social activities). The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (no interference) to 6 (extreme interference).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Support From Baseline to Week 6	Appraisal of support received from spouse, family and significant others. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (no support) to 6 (very much support).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Support Which the Patient Received From Baseline to Week 12	Appraisal of support received from spouse, family and significant others. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (no support) to 6 (very much support).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (not at all strong) to 6 (very strong).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (no control) to 6 (extreme control).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 6	Perceived life control and ability to solve problems and feelings of personal mastery and competence. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (no control) to 6 (extreme control).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 12	Perceived life control and ability to solve problems and feelings of personal mastery and competence. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (no control) to 6 (extreme control).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 6	Affective distress, including ratings of depressed mood, irritability, and tension. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (no distress) to 6 (extreme distress).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 12	Affective distress, including ratings of depressed mood, irritability, and tension. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (no distress) to 6 (extreme distress).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 6	Degree to which significant others display negative responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 12	Degree to which significant others display negative responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 6	Degree to which significant others display solicitous responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 12	Degree to which significant others display solicitous responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	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	Degree to which significant others display distracting responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	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	Degree to which significant others display distracting responses to the patient's pain behaviors and complaints. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 6	Frequency with which the patient engages in household chores. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 12	Frequency with which the patient engages in household chores. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 6	Frequency with which the patient engages in outdoor work. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 12	Frequency with which the patient engages in outdoor work. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 6	Frequency with which the patient engages in social activities. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 12	Frequency with which the patient engages in social activities. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 6	Frequency with which the patient engages in general activities. The change from baseline reflects the week 6 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 6	No
Secondary	Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 12	Frequency with which the patient engages in general activities. The change from baseline reflects the week 12 value minus the baseline value. The scores range from 0 (never) to 6 (very frequently).	Baseline and Week 12	No
Secondary	Change in Clinical Global Impression - Severity Pain From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. The score of the Clinical global impression ranges from 1 (not ill at all) to 7 (extremely ill).	Baseline and Week 2	No
Secondary	Change in Clinical Global Impression - Severity Pain From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. The score of the Clinical global impression ranges from 1 (not ill at all) to 7 (extremely ill).	Baseline and Week 6	No
Secondary	Change in Clinical Global Impression - Severity Pain From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. The score of the Clinical global impression ranges from 1 (not ill at all) to 7 (extremely ill).	Baseline and Week 12	No
Secondary	Change in Hamilton Depression Score From Baseline to Week 2	The change from baseline reflects the week 2 value minus the baseline value. A lower score corresponds to a lower level of depression. The score ranges from 0 to 52.	Baseline and Week 2	No
Secondary	Change in Hamilton Depression Score From Baseline to Week 6	The change from baseline reflects the week 6 value minus the baseline value. A lower score corresponds to a lower level of depression. The score ranges from 0 to 52.	Baseline and Week 6	No
Secondary	Change in Hamilton Depression Score From Baseline to Week 12	The change from baseline reflects the week 12 value minus the baseline value. A lower score corresponds to a lower level of depression. The score ranges from 0 to 52.	Baseline and Week 12	No
Secondary	Suicidal Thoughts by BDI-II at Week 2		Week 2	No
Secondary	Suicidal Thoughts by BDI-II at Week 6		Week 6	No
Secondary	Suicidal Thoughts by BDI-II at Week 12		Week 12	No
Secondary	Suicidal Thoughts or Behaviours by HAMD-17 at Week 2		Week 2	No
Secondary	Suicidal Thoughts or Behaviours by HAMD-17 at Week 6		Week 6	No
Secondary	Suicidal Thoughts or Behaviours by HAMD-17 at Week 12		Week 12	No
Secondary	Change of Fasting Blood Glucose From Baseline at Week 12	Ancova analysis controlling for baseline and insulin intake	Baseline and Week 12	No
Secondary	Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline at Week 12	Ancova analysis controlling for baseline and insulin intake	Baseline and Week 12	No
Secondary	Change of Systolic Blood Pressure From Baseline at Week 12		Baseline and Week 12	No
Secondary	Change of Diastolic Blood Pressure From Baseline at Week 12		Baseline and Week 12	No
Secondary	Change of Pulse Rate From Baseline at Week 12		Baseline and Week 12	No