Recruitment

Recruitment Status
Terminated
Estimated Enrollment
40

Inclusion Criterias

3 months of continuous opioid therapy for chronic pain;
Females must (a) be using birth control pills or depo provera injections, or have an intrauterine device; or (b) be post-menopausal, or (c) have undergone surgically sterilization.
Aged 18 and older
...
3 months of continuous opioid therapy for chronic pain;
Females must (a) be using birth control pills or depo provera injections, or have an intrauterine device; or (b) be post-menopausal, or (c) have undergone surgically sterilization.
Aged 18 and older
Primary care provider's (PCP) assent for patient participation, ascertained via encrypted email or in-person query.
28 (out of 70) on the 7-item Brief Pain Inventory (BPI) functional interference subscale at screening
30-100 mg morphine equivalent daily opioid dose based on pharmacy records of standing and as needed opioids prescribed.
Numerical pain rating of 4 or greater (i.e., moderate pain or greater) at screening on the 11-point pain numerical rating scale (NRS)

Exclusion Criterias

Recently decompensated medical illness necessitating inpatient hospitalization (past 30 days)
Pregnancy or lactation
Transaminases (aspartate aminotransferase/alanine aminotransferase) greater than five times the upper limit of normal within 90 days of assessment phase
...
Recently decompensated medical illness necessitating inpatient hospitalization (past 30 days)
Pregnancy or lactation
Transaminases (aspartate aminotransferase/alanine aminotransferase) greater than five times the upper limit of normal within 90 days of assessment phase
Opioid therapy for palliative care
Use of a moderate to strong CYP3A4 inhibitor
Not well-controlled psychiatric symptoms at the time of physician assessment, including suicidal ideation or untreated psychosis; or recently decompensated psychiatric illness necessitating inpatient hospitalization (past 30 days).
DSM-IV defined substance use disorder, except nicotine dependence. Participants known to using marijuana, including those who are apparently legally authorized to use marijuana by non-VHA providers, will be excluded since opioid dose escalation in regular marijuana users is contraindicated.
Participation in another investigational pharmaceutical trial within 30 days of screening

Summary

Conditions
Pain
Type
Interventional
Phase
Phase 4
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

Increasingly, Veterans are prescribed potent opioid analgesics for the treatment of chronic pain despite limited evidence for efficacy and increasing evidence of serious harms including addiction and non-fatal and fatal overdose. While guidelines recommend consideration of dose increase for patients...

Increasingly, Veterans are prescribed potent opioid analgesics for the treatment of chronic pain despite limited evidence for efficacy and increasing evidence of serious harms including addiction and non-fatal and fatal overdose. While guidelines recommend consideration of dose increase for patients not benefitting from opioid therapy, the rates of major harms are directly related to dose. Higher doses may also be more likely to precipitate opioid-induced hyperalgesia, a paradoxical increased pain response, in susceptible individuals. In summary, opioid dose increase, a currently accepted clinical response to poorly controlled pain, may offer little benefit and certainly increases risk, especially in patients already on moderate-high doses (30-100 mg daily morphine equivalents). Alternative treatment strategies to opioid dose escalation that lessen risk and possibly increase benefit are much needed. Switching to buprenorphine/naloxone (BUP/NX), a partial opioid agonist approved for use in the treatment of opioid abuse/dependence, may be a safe and effective alternative strategy to opioid dose escalation in the treatment of chronic pain. As a partial agonist, there is a ceiling to BUP/NX's respiratory depressant and other opioid-like effects, meaning it is less likely to cause addiction and overdose. Additionally, there are pre-clinical data to suggest BUP/NX is less likely to produce opioid-induced hyperalgesia and may even reverse it in patients switched from full agonist opioids. Case series have demonstrated improvements in pain, functional status and quality of life among patients switched from full agonist opioids to BUP/NX for chronic pain. Controlled trials are needed to establish BUP/NX's efficacy compared to opioid dose escalation in the treatment of poorly-controlled pain. The investigators propose a pilot 12-week, open label randomized trial of BUP/NX compared to opioid dose escalation among patients with poorly-controlled pain on the primary outcome of pain intensity. As patient acceptance of either opioid dose escalation or BUP/NX is unknown, the investigators' first objective is to assess willingness to enroll in a randomized trial and reasons for and against enrollment among eligible patients. The study will compare treatments on the primary outcome of pain intensity, measured using the 11-point pain numerical rating scale, and secondary outcomes of pain interference, using the Brief Pain Inventory functional interference subscale, medication adherence and patient global assessment of change. Mixed models will be employed in the analysis to accommodate potential unbalanced repeated measures with missing data. Effect size estimates will be used to generate sample size projections for a definitive trial. This line of research is a direct extension of the PI's HSR&D-funded CDA-2 project developing a screening tool to identify low efficacy opioid use in primary care and also well-aligned with the Strategic Plan and Focused Area of Research of the Pain Research, Informatics, Medical comorbidities, and Education (PRIME) Center's proposal for a Center of Innovation (COIN) and its strategic objective to "Promote access, continuity, and sustainability of safe and effective interventions for pain and pain-related disability."

Inclusion Criterias

3 months of continuous opioid therapy for chronic pain;
Females must (a) be using birth control pills or depo provera injections, or have an intrauterine device; or (b) be post-menopausal, or (c) have undergone surgically sterilization.
Aged 18 and older
...
3 months of continuous opioid therapy for chronic pain;
Females must (a) be using birth control pills or depo provera injections, or have an intrauterine device; or (b) be post-menopausal, or (c) have undergone surgically sterilization.
Aged 18 and older
Primary care provider's (PCP) assent for patient participation, ascertained via encrypted email or in-person query.
28 (out of 70) on the 7-item Brief Pain Inventory (BPI) functional interference subscale at screening
30-100 mg morphine equivalent daily opioid dose based on pharmacy records of standing and as needed opioids prescribed.
Numerical pain rating of 4 or greater (i.e., moderate pain or greater) at screening on the 11-point pain numerical rating scale (NRS)

Exclusion Criterias

Recently decompensated medical illness necessitating inpatient hospitalization (past 30 days)
Pregnancy or lactation
Transaminases (aspartate aminotransferase/alanine aminotransferase) greater than five times the upper limit of normal within 90 days of assessment phase
...
Recently decompensated medical illness necessitating inpatient hospitalization (past 30 days)
Pregnancy or lactation
Transaminases (aspartate aminotransferase/alanine aminotransferase) greater than five times the upper limit of normal within 90 days of assessment phase
Opioid therapy for palliative care
Use of a moderate to strong CYP3A4 inhibitor
Not well-controlled psychiatric symptoms at the time of physician assessment, including suicidal ideation or untreated psychosis; or recently decompensated psychiatric illness necessitating inpatient hospitalization (past 30 days).
DSM-IV defined substance use disorder, except nicotine dependence. Participants known to using marijuana, including those who are apparently legally authorized to use marijuana by non-VHA providers, will be excluded since opioid dose escalation in regular marijuana users is contraindicated.
Participation in another investigational pharmaceutical trial within 30 days of screening

Locations

West Haven, Connecticut, 06516
West Haven, Connecticut, 06516

Tracking Information

NCT #
NCT01875848
Collaborators
Not Provided
Investigators
  • Principal Investigator: William C Becker, MD VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • William C Becker, MD VA Connecticut Healthcare System West Haven Campus, West Haven, CT