Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00108550
Status:
COMPLETED
Last Update Posted:
2014-02-10
First Post:
2005-04-15
Brief Title:
Chronic Low Back Pain Research Project
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Efficacy of Antidepressants in Chronic Back Pain
Status:
COMPLETED
Status Verified Date:
2013-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether gabapentin is efficacious as an analgesic for chronic low back pain
Detailed Description:
Chronic low back pain CLBP is a major health problem for the VA affecting up to 15 of all veterans Nationally its medical and disability costs exceed 50 billion annually Despite its impact relatively little research evaluates treatment for CLBP Wide variation in patterns of care suggests uncertainty over effective therapy Most chronic back cases are not surgical candidates The mainstays of medical treatment have been non-steroidal anti-inflammatory drugs NSAIDs muscle relaxants opioids and antidepressants Non-steroidal drugs and muscle relaxants are effective for acute but not for chronic back pain Opioids may provide analgesia but safety limits their use Tricyclic antidepressants provide modest pain relief separate from effects on depression But it is clear additional research is needed to develop more effective pharmacotherapy One approach favored by many authorities is determining if agents effective for one type of chronic pain syndrome eg diabetic neuropathy can be generalized to other syndromes like chronic back pain Another is to identify effective drug combinations based on selecting drugs with differing therapeutic mechanisms
This research is a program of rigorous randomized clinical trials testing the efficacy of antidepressants for analgesia in chronic back pain Because chronic pain is a complex disorder the program features a multidisciplinary research team involving specialists in psychiatry orthopedic surgery psychology anesthesiology clinical pharmacology and biomathematics The research has both pragmatic and explanatory aims Our strategy has been to test antidepressants with differing and selective properties in an attempt to isolate therapeutic mechanisms Thus we began with trials using selective norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors SSRIs rather than those with dual noradrenergic and serotonergic effects eg amitriptyline imipramine To ensure applicability of results we have used rigorous diagnostic procedures to identify patients with chronic back pain due to degenerative disk disease To enhance generalizability we recruit primary care patients rather than tertiary pain clinic samples Patients without major depression are studied to examine analgesia separate from antidepressant effects Secondary outcomes address function and life quality
We have conducted three controlled trials using identical recruitment and assessment methodology The first comparing a noradrenergic antidepressant nortriptyline with placebo indicated that the noradrenergic agent provided clinically relevant analgesia The second was a head-to-head comparison of a selective noradrenergic agent maprotiline with a selective serotonin reuptake inhibitor SSRI paroxetine The noradrenergic agent outperformed the SSRI which was equivalent to placebo To clarify these results we explored whether efficacy might be evident only at specific drug concentrations Therefore the third study has a prospective concentration design comparing the most potent and selective noradrenergic antidepressant desipramine to the standard SSRI fluoxetine Subjects were randomized to placebo or predetermined concentration windows reflecting low medium and high exposure to study drugs and followed for 12 weeks Interim analysis suggests that low concentration desipramine outperforms placebo p005 It is also superior to mid-concentration and high exposure desipramine--as well as all exposure levels of the SSRI which are equivalent to placebo
In sum all three studies supported noradrenergic analgesia in CLBP and the two studies that evaluated SSRIs failed to find analgesia This suggests noradrenergic activity perhaps within a therapeutic window may be primarily responsible for back pain analgesia These findings have led us away from studies proposing combining noradrenergic and serotonergic agents An alternative approach which builds on these data but first employs another class of agents seems reasonable This strategy is to assess if gabapentin a calcium channel blocker agent with demonstrated efficacy in neuropathic pain can be extended to chronic back pain
We conducted a double-blind randomized assignment 12-week placebo controlled clinical trial of the efficacy of gabapentin Non-depressed chronic low back pain patients N 130 will be randomized to placebo or high dose gabapentin 3600 mgday or maximum tolerable dose Analysis was by intent to treat The primary efficacy assessment is mean pain intensity Descriptor Differential Scale DDS at exit Secondary outcomes are function and life quality Oswestry Disability Index Short Form-36 Quality of Well-Being Scale Safety evaluation includes rating adverse events Scandinavian Society of Psychopharmacology Committee on Clinical Investiagations Side Effects Rating Scale UKU standardized physical examination and clinical laboratory testing Results could provide explanatory insight into mechanisms of back pain and address the pragmatic clinical need by primary care providers and others for effective therapy
This research is a program of rigorous randomized clinical trials testing the efficacy of antidepressants for analgesia in chronic back pain Because chronic pain is a complex disorder the program features a multidisciplinary research team involving specialists in psychiatry orthopedic surgery psychology anesthesiology clinical pharmacology and biomathematics The research has both pragmatic and explanatory aims Our strategy has been to test antidepressants with differing and selective properties in an attempt to isolate therapeutic mechanisms Thus we began with trials using selective norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors SSRIs rather than those with dual noradrenergic and serotonergic effects eg amitriptyline imipramine To ensure applicability of results we have used rigorous diagnostic procedures to identify patients with chronic back pain due to degenerative disk disease To enhance generalizability we recruit primary care patients rather than tertiary pain clinic samples Patients without major depression are studied to examine analgesia separate from antidepressant effects Secondary outcomes address function and life quality
We have conducted three controlled trials using identical recruitment and assessment methodology The first comparing a noradrenergic antidepressant nortriptyline with placebo indicated that the noradrenergic agent provided clinically relevant analgesia The second was a head-to-head comparison of a selective noradrenergic agent maprotiline with a selective serotonin reuptake inhibitor SSRI paroxetine The noradrenergic agent outperformed the SSRI which was equivalent to placebo To clarify these results we explored whether efficacy might be evident only at specific drug concentrations Therefore the third study has a prospective concentration design comparing the most potent and selective noradrenergic antidepressant desipramine to the standard SSRI fluoxetine Subjects were randomized to placebo or predetermined concentration windows reflecting low medium and high exposure to study drugs and followed for 12 weeks Interim analysis suggests that low concentration desipramine outperforms placebo p005 It is also superior to mid-concentration and high exposure desipramine--as well as all exposure levels of the SSRI which are equivalent to placebo
In sum all three studies supported noradrenergic analgesia in CLBP and the two studies that evaluated SSRIs failed to find analgesia This suggests noradrenergic activity perhaps within a therapeutic window may be primarily responsible for back pain analgesia These findings have led us away from studies proposing combining noradrenergic and serotonergic agents An alternative approach which builds on these data but first employs another class of agents seems reasonable This strategy is to assess if gabapentin a calcium channel blocker agent with demonstrated efficacy in neuropathic pain can be extended to chronic back pain
We conducted a double-blind randomized assignment 12-week placebo controlled clinical trial of the efficacy of gabapentin Non-depressed chronic low back pain patients N 130 will be randomized to placebo or high dose gabapentin 3600 mgday or maximum tolerable dose Analysis was by intent to treat The primary efficacy assessment is mean pain intensity Descriptor Differential Scale DDS at exit Secondary outcomes are function and life quality Oswestry Disability Index Short Form-36 Quality of Well-Being Scale Safety evaluation includes rating adverse events Scandinavian Society of Psychopharmacology Committee on Clinical Investiagations Side Effects Rating Scale UKU standardized physical examination and clinical laboratory testing Results could provide explanatory insight into mechanisms of back pain and address the pragmatic clinical need by primary care providers and others for effective therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None